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Reading data

Get bulk export from bugsigdb.org:

full.dat <- bugsigdbr::importBugSigDB(version = "devel", cache = FALSE)
dim(full.dat)
## [1] 13573    51
colnames(full.dat)
##  [1] "BSDB ID"                    "Study"                     
##  [3] "Study design"               "PMID"                      
##  [5] "DOI"                        "URL"                       
##  [7] "Authors list"               "Title"                     
##  [9] "Journal"                    "Year"                      
## [11] "Keywords"                   "Experiment"                
## [13] "Location of subjects"       "Host species"              
## [15] "Body site"                  "UBERON ID"                 
## [17] "Condition"                  "EFO ID"                    
## [19] "Group 0 name"               "Group 1 name"              
## [21] "Group 1 definition"         "Group 0 sample size"       
## [23] "Group 1 sample size"        "Antibiotics exclusion"     
## [25] "Sequencing type"            "16S variable region"       
## [27] "Sequencing platform"        "Data transformation"       
## [29] "Statistical test"           "Significance threshold"    
## [31] "MHT correction"             "LDA Score above"           
## [33] "Matched on"                 "Confounders controlled for"
## [35] "Pielou"                     "Shannon"                   
## [37] "Chao1"                      "Simpson"                   
## [39] "Inverse Simpson"            "Richness"                  
## [41] "Signature page name"        "Source"                    
## [43] "Curated date"               "Curator"                   
## [45] "Revision editor"            "Description"               
## [47] "Abundance in Group 1"       "MetaPhlAn taxon names"     
## [49] "NCBI Taxonomy IDs"          "State"                     
## [51] "Reviewer"

Stripping illformed entries:

is.study <- !is.na(full.dat[["Study"]])
is.exp <- !is.na(full.dat[["Experiment"]])
full.dat <- full.dat[is.study & is.exp, ]

Curation output

Number of papers and signatures curated:

pmids <- unique(full.dat[,"PMID"])
length(pmids)
## [1] 1998
nrow(full.dat)
## [1] 13573

Publication date of the curated papers:

pmids <- pmids[!is.na(pmids)]
pubyear <- pmid2pubyear(pmids)
head(cbind(pmids, pubyear))
tab <- table(pubyear)
tab <- tab[order(as.integer(names(tab)))]
df <- data.frame(year = names(tab), papers = as.integer(tab))
ggbarplot(df, x = "year", y = "papers", 
          label = TRUE, fill = "steelblue",
          ggtheme = theme_bw())

Stripping empty signatures:

ind1 <- lengths(full.dat[["MetaPhlAn taxon names"]]) > 0
ind2 <- lengths(full.dat[["NCBI Taxonomy IDs"]]) > 0
dat <- full.dat[ind1 & ind2,]
nrow(dat)
## [1] 13573

Papers containing only empty UP and DOWN signatures (under curation?):

setdiff(pmids, unique(dat[,"PMID"]))
## character(0)

Progress over time:

dat[,"Curated date"] <- as.character(lubridate::dmy(dat[,"Curated date"]))
plotProgressOverTime(dat)

plotProgressOverTime(dat, diff = TRUE)

Stratified by curator:

npc <- stratifyByCurator(dat)
plotCuratorStats(dat, npc)

Number of complete and revised signatures: Turned off because it’s way too long these days

table(dat[["State"]])
table(dat[,"Revision editor"])

Study stats

Study design

spl <- split(dat[["Study"]], dat[["Study design"]])
sds <- lapply(spl, unique)
sort(lengths(sds), decreasing = FALSE)
##              cross-sectional observational, not case-control,randomized controlled trial 
##                                                                                        1 
##                                                 laboratory experiment,prospective cohort 
##                                                                                        1 
##                                        laboratory experiment,randomized controlled trial 
##                                                                                        1 
##                                                         meta-analysis,prospective cohort 
##                                                                                        1 
##                                                 prospective cohort,laboratory experiment 
##                                                                                        1 
##                                                 randomized controlled trial,case-control 
##                                                                                        1 
## time series / longitudinal observational,cross-sectional observational, not case-control 
##                                                                                        1 
##                                                          case-control,prospective cohort 
##                                                                                        2 
##                    cross-sectional observational, not case-control,laboratory experiment 
##                                                                                        2 
##                    laboratory experiment,cross-sectional observational, not case-control 
##                                                                                        2 
##                                                      meta-analysis,laboratory experiment 
##                                                                                        2 
##                       prospective cohort,cross-sectional observational, not case-control 
##                                                                                        2 
##                     randomized controlled trial,time series / longitudinal observational 
##                                                                                        2 
##                                    time series / longitudinal observational,case-control 
##                                                                                        2 
##                                        randomized controlled trial,laboratory experiment 
##                                                                                        3 
##                              time series / longitudinal observational,prospective cohort 
##                                                                                        3 
##                           laboratory experiment,time series / longitudinal observational 
##                                                                                        4 
##                                                               meta-analysis,case-control 
##                                                                                        4 
##                           time series / longitudinal observational,laboratory experiment 
##                                                                                        4 
##                                                               case-control,meta-analysis 
##                                                                                        5 
##                                                       laboratory experiment,case-control 
##                                                                                        6 
##                                                       case-control,laboratory experiment 
##                                                                                        7 
##                                    case-control,time series / longitudinal observational 
##                                                                                        8 
##                                                                            meta-analysis 
##                                                                                       31 
##                                                              randomized controlled trial 
##                                                                                       90 
##                                                 time series / longitudinal observational 
##                                                                                      151 
##                                                                       prospective cohort 
##                                                                                      157 
##                                                                    laboratory experiment 
##                                                                                      222 
##                                          cross-sectional observational, not case-control 
##                                                                                      508 
##                                                                             case-control 
##                                                                                      781

Experiment stats

Columns of the full dataset that describe experiments:

# Experiment ID
exp.cols <- c("Study", "Experiment")

# Subjects
sub.cols <- c("Host species",    
              "Location of subjects", 
              "Body site",
              "Condition", 
              "Antibiotics exclusion",
              "Group 0 sample size",
              "Group 1 sample size")

# Lab analysis              
lab.cols <-  c("Sequencing type",
              "16S variable region",
              "Sequencing platform")

# Statistical analysis
stat.cols <-  c("Statistical test",
              "MHT correction",
              "Significance threshold")

# Alpha diversity
div.cols <- c("Pielou",
              "Shannon",
              "Chao1",
              "Simpson", 
              "Inverse Simpson",
              "Richness")

Restrict dataset to experiment information:

exps <- dat[,c(exp.cols, sub.cols, lab.cols, stat.cols, div.cols)]
exps <- unique(exps)

Subjects

Number of experiments for the top 10 categories for each subjects column:

sub.tab <- lapply(sub.cols[1:5], tabCol, df = exps, n = 10)
names(sub.tab) <- sub.cols[1:5]
sub.tab
## $`Host species`
## 
##           Homo sapiens           Mus musculus      Rattus norvegicus 
##                   6434                    926                    217 
##  Sus scrofa domesticus Canis lupus familiaris          Not specified 
##                    140                    134                     42 
##         Macaca mulatta             Ovis aries             Bos taurus 
##                     33                     28                     24 
##    Macaca fascicularis 
##                     24 
## 
## $`Location of subjects`
## 
##                    China United States of America                    Japan 
##                     3066                     1163                      309 
##                  Germany                    Italy                  Denmark 
##                      200                      190                      183 
##                    Spain              South Korea                Australia 
##                      178                      159                      150 
##           United Kingdom 
##                      137 
## 
## $`Body site`
## 
##                     Feces                    Saliva                    Vagina 
##                      5187                       443                       173 
## Subgingival dental plaque                    Caecum               Oral cavity 
##                       135                        91                        83 
##               Nasopharynx                     Mouth                     Colon 
##                        80                        67                        65 
##                    Rectum 
##                        56 
## 
## $Condition
## 
##                      Diet       Parkinson's disease         Colorectal cancer 
##                       286                       233                       207 
##                   Obesity                  COVID-19    Response to transplant 
##                       163                       127                       110 
##          Response to diet Polycystic ovary syndrome Type II diabetes mellitus 
##                       103                        99                        93 
##              Constipation 
##                        91 
## 
## $`Antibiotics exclusion`
## 
##                         3 months                          1 month 
##                             1194                              959 
##                         2 months                         6 months 
##                              340                              324 
##                          2 weeks                           1 week 
##                              228                               36 
##        Recent use of antibiotics         currently on antibiotics 
##                               34                               24 
##                           1 year more than 5 days during 6 months 
##                               22                               19

Proportions instead:

sub.tab <- lapply(sub.cols[1:5], tabCol, df = exps, n = 10, perc = TRUE)
names(sub.tab) <- sub.cols[1:5]
sub.tab
## $`Host species`
## 
##           Homo sapiens           Mus musculus      Rattus norvegicus 
##                0.77400                0.11100                0.02610 
##  Sus scrofa domesticus Canis lupus familiaris          Not specified 
##                0.01680                0.01610                0.00505 
##         Macaca mulatta             Ovis aries             Bos taurus 
##                0.00397                0.00337                0.00289 
##    Macaca fascicularis 
##                0.00289 
## 
## $`Location of subjects`
## 
##                    China United States of America                    Japan 
##                   0.3690                   0.1400                   0.0372 
##                  Germany                    Italy                  Denmark 
##                   0.0241                   0.0229                   0.0220 
##                    Spain              South Korea                Australia 
##                   0.0214                   0.0191                   0.0181 
##           United Kingdom 
##                   0.0165 
## 
## $`Body site`
## 
##                     Feces                    Saliva                    Vagina 
##                   0.62700                   0.05350                   0.02090 
## Subgingival dental plaque                    Caecum               Oral cavity 
##                   0.01630                   0.01100                   0.01000 
##               Nasopharynx                     Mouth                     Colon 
##                   0.00967                   0.00810                   0.00785 
##                    Rectum 
##                   0.00677 
## 
## $Condition
## 
##                      Diet       Parkinson's disease         Colorectal cancer 
##                    0.0353                    0.0287                    0.0255 
##                   Obesity                  COVID-19    Response to transplant 
##                    0.0201                    0.0157                    0.0136 
##          Response to diet Polycystic ovary syndrome Type II diabetes mellitus 
##                    0.0127                    0.0122                    0.0115 
##              Constipation 
##                    0.0112 
## 
## $`Antibiotics exclusion`
## 
##                         3 months                          1 month 
##                          0.34500                          0.27700 
##                         2 months                         6 months 
##                          0.09830                          0.09370 
##                          2 weeks                           1 week 
##                          0.06590                          0.01040 
##        Recent use of antibiotics         currently on antibiotics 
##                          0.00983                          0.00694 
##                           1 year more than 5 days during 6 months 
##                          0.00636                          0.00549

Sample size:

ssize <- apply(exps[,sub.cols[6:7]], 2, summary)
ssize
##         Group 0 sample size Group 1 sample size
## Min.                 0.0000             1.00000
## 1st Qu.             11.0000            10.00000
## Median              24.0000            21.00000
## Mean               401.2697            61.64559
## 3rd Qu.             49.0000            41.00000
## Max.            308633.0000         10413.00000
## NA's              1413.0000          1406.00000

Lab analysis

Number of experiments for the top 10 categories for each lab analysis column:

lab.tab <- lapply(lab.cols, tabCol, df = exps, n = 10)
names(lab.tab) <- lab.cols
lab.tab
## $`Sequencing type`
## 
##        16S        WMS        PCR ITS / ITS2        18S 
##       6585       1300         79         76          5 
## 
## $`16S variable region`
## 
##        34         4        12       123        45       345 123456789         3 
##      3111      1611       355       244       214       149       116        77 
##        56  23456789 
##        52        37 
## 
## $`Sequencing platform`
## 
##                              Illumina                              Roche454 
##                                  6826                                   339 
##                           Ion Torrent                               RT-qPCR 
##                                   279                                   156 
##                              Nanopore PacBio Vega (VS)/Revio (RS)/Sequel II 
##                                    70                                    45 
##                           MGISEQ-2000           Human Intestinal Tract Chip 
##                                    38                                    31 
##                 BGISEQ-500 Sequencing                     Mass spectrometry 
##                                    21                                    18

Proportions instead:

lab.tab <- lapply(lab.cols, tabCol, df = exps, n = 10, perc = TRUE)
names(lab.tab) <- lab.cols
lab.tab
## $`Sequencing type`
## 
##        16S        WMS        PCR ITS / ITS2        18S 
##   0.819000   0.162000   0.009820   0.009450   0.000622 
## 
## $`16S variable region`
## 
##        34         4        12       123        45       345 123456789         3 
##   0.50900   0.26300   0.05800   0.03990   0.03500   0.02440   0.01900   0.01260 
##        56  23456789 
##   0.00850   0.00605 
## 
## $`Sequencing platform`
## 
##                              Illumina                              Roche454 
##                               0.86300                               0.04290 
##                           Ion Torrent                               RT-qPCR 
##                               0.03530                               0.01970 
##                              Nanopore PacBio Vega (VS)/Revio (RS)/Sequel II 
##                               0.00885                               0.00569 
##                           MGISEQ-2000           Human Intestinal Tract Chip 
##                               0.00481                               0.00392 
##                 BGISEQ-500 Sequencing                     Mass spectrometry 
##                               0.00266                               0.00228

Statistical analysis

Number of experiments for the top 10 categories for each statistical analysis column:

# Define the columns to analyze
stat.cols <- c("Statistical test", "MHT correction", "Significance threshold")
# Get top 10 counts
stat.tab.count <- lapply(stat.cols, tabCol, df = exps, n = 10)
names(stat.tab.count) <- stat.cols
# Get top 10 proportions
stat.tab.prop <- lapply(stat.cols, tabCol, df = exps, n = 10, perc = TRUE)
names(stat.tab.prop) <- stat.cols

Top 10 Counts

count_df <- data.frame(
  Name = names(stat.tab.count[["Statistical test"]]), 
  Count = as.vector(stat.tab.count[["Statistical test"]])
)
DT::datatable(
  count_df,
  rownames = FALSE,
  options = list(pageLength = 10),
  caption = "Top categories for: Statistical test"
)
count_df <- data.frame(
  Name = names(stat.tab.count[["MHT correction"]]), 
  Count = as.vector(stat.tab.count[["MHT correction"]])
)
DT::datatable(
  count_df,
  rownames = FALSE,
  options = list(pageLength = 10),
  caption = "Top categories for: MHT correction"
)
count_df <- data.frame(
  Value = names(stat.tab.count[["Significance threshold"]]), 
  Count = as.vector(stat.tab.count[["Significance threshold"]])
)
DT::datatable(
  count_df,
  rownames = FALSE,
  options = list(pageLength = 10),
  caption = "Top categories for: Significance threshold"
)

Top 10 Proportions

prop_df <- data.frame(
  Name = names(stat.tab.prop[["Statistical test"]]), 
  Proportion = as.vector(stat.tab.prop[["Statistical test"]])
)
DT::datatable(
  prop_df,
  rownames = FALSE,
  options = list(pageLength = 10),
  caption = "Top proportions for: Statistical test"
)
prop_df <- data.frame(
  Name = names(stat.tab.prop[["MHT correction"]]), 
  Proportion = as.vector(stat.tab.prop[["MHT correction"]])
)
DT::datatable(
  prop_df,
  rownames = FALSE,
  options = list(pageLength = 10),
  caption = "Top proportions for: MHT correction"
)
prop_df <- data.frame(
  Value = names(stat.tab.prop[["Significance threshold"]]), 
  Proportion = as.vector(stat.tab.prop[["Significance threshold"]])
)
DT::datatable(
  prop_df,
  rownames = FALSE,
  options = list(pageLength = 10),
  caption = "Top proportions for: Significance threshold"
)

Alpha diversity

Overall distribution:

apply(exps[,div.cols], 2, table)
##           Pielou Shannon Chao1 Simpson Inverse Simpson Richness
## decreased     93     924   589     333              79      598
## increased     64     726   432     197              61      435
## unchanged    322    2691  1294    1034             277     1397

Correspondence of Shannon diversity and Richness:

table(exps$Shannon, exps$Richness)
##            
##             decreased increased unchanged
##   decreased       328        15        73
##   increased        16       216        68
##   unchanged       126       115      1123

Conditions with consistently increased or decreased alpha diversity:

tabDiv(exps, "Shannon", "Condition")
##                                                           increased decreased
## Pulmonary tuberculosis                                            4        25
## Polycystic ovary syndrome                                         4        19
## Gastric cancer                                                    6        20
## COVID-19                                                         11        24
## Periodontitis                                                    16         3
## Diet                                                             19        31
## HIV infection                                                     1        12
## Ulcerative colitis                                                1        12
## Clostridium difficile infection                                  10         0
## Crohn's disease                                                   0        10
## Multiple sclerosis                                                2        12
## Obesity                                                           7        17
## Systemic inflammatory response syndrome                           5        15
## Alzheimer's disease                                               2        11
## Chronic constipation                                              9         0
## Human papilloma virus infection                                  10         1
## Gingivitis                                                        1         9
## Pancreatic carcinoma                                              9         1
## Smoking behaviour measurement                                     8         0
## Age                                                               6        13
## Dry eye syndrome                                                  1         8
## Heart failure                                                     0         7
## Lung cancer                                                       2         9
## Mycobacterium tuberculosis                                        7         0
## Atopic eczema                                                     5        11
## Autism spectrum disorder                                          7         1
## Cesarean section                                                  6         0
## Graves disease                                                    1         7
## Parkinson's disease                                              20        14
## Response to allogeneic hematopoietic stem cell transplant         0         6
## Spontaneous preterm birth                                        13         7
## Acute pancreatitis                                                0         5
## Aging                                                             2         7
## Bronchiectasis                                                    0         5
## Cervical cancer                                                   5         0
## Constipation                                                      8         3
## Epilepsy                                                          5         0
## Helminthiasis                                                     5         0
## Oxygen                                                            5         0
## Response to antibiotic                                            2         7
## Species design                                                   10        15
## Urinary tract infection                                           1         6
## Acute lymphoblastic leukemia                                      0         4
## Body mass index                                                   0         4
## Chronic kidney disease                                            2         6
## Colitis                                                           4         0
## Colorectal cancer                                                18        14
## Cystic fibrosis                                                   0         4
## Ethnic group                                                      3         7
## Food allergy                                                      6         2
## Gestational diabetes                                              4         0
## Hepatocellular carcinoma                                          4         8
## Human immunodeficiency virus                                      0         4
## Inflammatory bowel disease                                        0         4
## Pregnancy                                                         4         0
## Alcohol drinking                                                  3         0
## Antimicrobial agent                                               7        10
## Atopic asthma                                                     4         1
## Birth measurement                                                 3         0
## Chronic periodontitis                                             3         0
## Cognitive impairment                                              1         4
## Environmental exposure measurement                                3         0
## Extraction protocol                                              23        26
## Hematopoietic stem cell                                           0         3
## High fat diet                                                     4         1
## Hypertension                                                      7         4
## Hypothyroidism                                                    0         3
## Male homosexuality                                                3         0
## Peri-Implantitis                                                  3         0
## Response to antiviral drug                                        2         5
## SARS-CoV-2-related disease                                        0         3
## Schizophrenia                                                     1         4
## Smoking behavior                                                 10        13
## Traditional Chinese medicine type                                 2         5
## Tuberculosis                                                      2         5
## Acne                                                              0         2
## Age at assessment                                                 3         1
## Breed                                                             0         2
## Cervical glandular intraepithelial neoplasia                      2         0
## Chronic obstructive pulmonary disease                             4         2
## Compound based treatment                                          0         2
## Dental caries                                                     2         0
## Eczema                                                            0         2
## Endometrial cancer                                                4         2
## Environmental factor                                              7         5
## Esophageal adenocarcinoma                                         0         2
## Iron biomarker measurement                                        1         3
## Irritable bowel syndrome                                          5         7
## Lifestyle measurement                                             4         2
## Milk allergic reaction                                            2         0
## Non-alcoholic fatty liver disease                                 3         1
## Papillary thyroid carcinoma                                       2         0
## Phenotype                                                         2         0
## Phenylketonuria                                                   1         3
## Population                                                        5         7
## Reproductive behaviour measurement                                2         0
## Response to anti-tuberculosis drug                                8        10
## Response to immunochemotherapy                                    3         1
## Response to opioid                                                3         1
## Response to transplant                                           10         8
## Sampling site                                                     3         1
## Simian immunodeficiency virus infection                           0         2
## Sleep duration                                                    3         1
## Small for gestational age                                         0         2
## Smoking status measurement                                        2         0
## Squamous cell carcinoma                                           2         0
## Streptococcus pneumoniae                                          0         2
## Stroke                                                            2         0
## Acute respiratory failure                                         6         5
## Age-related macular degeneration                                  0         1
## Air pollution                                                     7         6
## Anxiety disorder                                                  0         1
## Attention deficit-hyperactivity disorder                          2         1
## Breast cancer                                                     4         5
## Breastfeeding duration                                            2         3
## Chronic fatigue syndrome                                          0         1
## Chronic hepatitis B virus infection                               0         1
## Clinical treatment                                                1         2
## Coccidiosis                                                       0         1
## Delivery method                                                   3         4
## Depressive disorder                                               1         2
## Diarrhea                                                          3         4
## Endometriosis                                                     2         3
## Esophageal cancer                                                 1         2
## Esophageal squamous cell carcinoma                                1         0
## Estradiol measurement                                             1         2
## Fasting                                                           0         1
## Female infertility                                                2         1
## Fungal infectious disease                                         2         1
## Glaucoma                                                          4         5
## Hypertrophy                                                       1         0
## Infant                                                            1         0
## Major depressive disorder                                         0         1
## Metastatic colorectal cancer                                      1         2
## Myocardial infarction                                             1         2
## Non-alcoholic steatohepatitis                                     1         2
## Obstructive sleep apnea                                           0         1
## Oral cavity carcinoma                                             0         1
## Oral squamous cell carcinoma                                      3         2
## Ovarian cancer                                                    4         3
## Pneumonia                                                         1         2
## Prediabetes syndrome                                              0         1
## Premature birth                                                   1         0
## Prostate cancer                                                   0         1
## Psoriasis                                                         1         0
## Respiratory Syncytial Virus Infection                             0         1
## Respiratory tract infectious disease                              0         1
## Response to stress                                                1         0
## Response to vaccine                                               1         2
## Sample treatment protocol                                         1         0
## Sampling time                                                     4         3
## Social interaction measurement                                    2         1
## Socioeconomic status                                              3         4
## Stimulus or stress design                                         0         1
## Timepoint                                                         1         0
## Treatment                                                         4         3
## Type I diabetes mellitus                                          0         1
## Vesicle membrane                                                  3         2
## Vitiligo                                                          0         1
## Abnormal stool composition                                        0         0
## Acute myeloid leukemia                                            1         1
## Alcohol use disorder measurement                                  2         2
## Arthritis                                                         0         0
## Asthma                                                            3         3
## Biological sex                                                    1         1
## Bipolar disorder                                                  0         0
## Celiac disease                                                    0         0
## Chlamydia trachomatis                                             2         2
## Colon carcinoma                                                   0         0
## Colorectal adenoma                                                2         2
## Contraception                                                     0         0
## COVID-19 symptoms measurement                                     0         0
## Diabetes mellitus                                                 1         1
## Diet measurement                                                  0         0
## Disease progression measurement                                   0         0
## Exposure                                                          1         1
## Gastric adenocarcinoma                                            0         0
## Glioma                                                            0         0
## Head and neck squamous cell carcinoma                             0         0
## Health study participation                                        3         3
## HIV mother to child transmission                                  0         0
## HIV-1 infection                                                   1         1
## Hydroxyproline measurement                                        1         1
## Hypertension, pregnancy-induced                                   0         0
## Hypoxia                                                           4         4
## Ischemic stroke                                                   0         0
## Lactose intolerance                                               0         0
## Lung transplantation                                              2         2
## Metabolic process                                                 0         0
## Neurodevelopmental delay                                          0         0
## Obsessive-compulsive disorder                                     0         0
## Oral lichen planus                                                3         3
## Oral mucositis                                                    2         2
## Oxalate measurement                                               1         1
## Postpartum                                                        0         0
## Psoriasis vulgaris                                                0         0
## Response to diet                                                  5         5
## Response to dietary antigen                                       0         0
## Response to ketogenic diet                                        2         2
## Rheumatoid arthritis                                              5         5
## Sample collection protocol                                        0         0
## SARS coronavirus                                                  0         0
## Social deprivation,Psychological measurement                      0         0
## Transplant outcome measurement                                    0         0
## Type II diabetes mellitus                                         7         7
## Vaginal microbiome measurement                                    0         0
## Viral load                                                        0         0
## Waist circumference                                               0         0
##                                                           unchanged
## Pulmonary tuberculosis                                           20
## Polycystic ovary syndrome                                        30
## Gastric cancer                                                   27
## COVID-19                                                         50
## Periodontitis                                                    16
## Diet                                                             85
## HIV infection                                                    27
## Ulcerative colitis                                                5
## Clostridium difficile infection                                   1
## Crohn's disease                                                  11
## Multiple sclerosis                                               32
## Obesity                                                          68
## Systemic inflammatory response syndrome                           4
## Alzheimer's disease                                              30
## Chronic constipation                                             12
## Human papilloma virus infection                                  28
## Gingivitis                                                       12
## Pancreatic carcinoma                                              6
## Smoking behaviour measurement                                     9
## Age                                                              12
## Dry eye syndrome                                                 14
## Heart failure                                                     2
## Lung cancer                                                       8
## Mycobacterium tuberculosis                                        5
## Atopic eczema                                                    72
## Autism spectrum disorder                                         12
## Cesarean section                                                 16
## Graves disease                                                    7
## Parkinson's disease                                              95
## Response to allogeneic hematopoietic stem cell transplant         0
## Spontaneous preterm birth                                         6
## Acute pancreatitis                                                3
## Aging                                                             2
## Bronchiectasis                                                    0
## Cervical cancer                                                   6
## Constipation                                                     13
## Epilepsy                                                          5
## Helminthiasis                                                     8
## Oxygen                                                            0
## Response to antibiotic                                           23
## Species design                                                   16
## Urinary tract infection                                          11
## Acute lymphoblastic leukemia                                     10
## Body mass index                                                   3
## Chronic kidney disease                                           11
## Colitis                                                           2
## Colorectal cancer                                                72
## Cystic fibrosis                                                   3
## Ethnic group                                                      6
## Food allergy                                                     19
## Gestational diabetes                                             36
## Hepatocellular carcinoma                                          7
## Human immunodeficiency virus                                      6
## Inflammatory bowel disease                                        1
## Pregnancy                                                         7
## Alcohol drinking                                                  2
## Antimicrobial agent                                              25
## Atopic asthma                                                     7
## Birth measurement                                                 4
## Chronic periodontitis                                             8
## Cognitive impairment                                             15
## Environmental exposure measurement                                4
## Extraction protocol                                              21
## Hematopoietic stem cell                                           3
## High fat diet                                                     2
## Hypertension                                                      8
## Hypothyroidism                                                    4
## Male homosexuality                                                6
## Peri-Implantitis                                                  2
## Response to antiviral drug                                       17
## SARS-CoV-2-related disease                                        5
## Schizophrenia                                                    24
## Smoking behavior                                                 21
## Traditional Chinese medicine type                                 8
## Tuberculosis                                                      0
## Acne                                                              3
## Age at assessment                                                 1
## Breed                                                             7
## Cervical glandular intraepithelial neoplasia                      9
## Chronic obstructive pulmonary disease                             5
## Compound based treatment                                          3
## Dental caries                                                     4
## Eczema                                                           10
## Endometrial cancer                                                3
## Environmental factor                                             18
## Esophageal adenocarcinoma                                         4
## Iron biomarker measurement                                        2
## Irritable bowel syndrome                                         28
## Lifestyle measurement                                            14
## Milk allergic reaction                                            5
## Non-alcoholic fatty liver disease                                 9
## Papillary thyroid carcinoma                                      10
## Phenotype                                                        19
## Phenylketonuria                                                   4
## Population                                                       28
## Reproductive behaviour measurement                                3
## Response to anti-tuberculosis drug                               13
## Response to immunochemotherapy                                    3
## Response to opioid                                                2
## Response to transplant                                           34
## Sampling site                                                     7
## Simian immunodeficiency virus infection                           9
## Sleep duration                                                    2
## Small for gestational age                                         6
## Smoking status measurement                                        4
## Squamous cell carcinoma                                           4
## Streptococcus pneumoniae                                          4
## Stroke                                                           16
## Acute respiratory failure                                         0
## Age-related macular degeneration                                  4
## Air pollution                                                     3
## Anxiety disorder                                                  7
## Attention deficit-hyperactivity disorder                          6
## Breast cancer                                                    31
## Breastfeeding duration                                            5
## Chronic fatigue syndrome                                          4
## Chronic hepatitis B virus infection                               5
## Clinical treatment                                                5
## Coccidiosis                                                       4
## Delivery method                                                  13
## Depressive disorder                                               8
## Diarrhea                                                          7
## Endometriosis                                                    14
## Esophageal cancer                                                 2
## Esophageal squamous cell carcinoma                                5
## Estradiol measurement                                             2
## Fasting                                                           4
## Female infertility                                                3
## Fungal infectious disease                                         4
## Glaucoma                                                          6
## Hypertrophy                                                       4
## Infant                                                            4
## Major depressive disorder                                         6
## Metastatic colorectal cancer                                      3
## Myocardial infarction                                            21
## Non-alcoholic steatohepatitis                                     8
## Obstructive sleep apnea                                          11
## Oral cavity carcinoma                                             7
## Oral squamous cell carcinoma                                      3
## Ovarian cancer                                                   35
## Pneumonia                                                         3
## Prediabetes syndrome                                              4
## Premature birth                                                   6
## Prostate cancer                                                   9
## Psoriasis                                                        14
## Respiratory Syncytial Virus Infection                             5
## Respiratory tract infectious disease                              5
## Response to stress                                                9
## Response to vaccine                                               5
## Sample treatment protocol                                         4
## Sampling time                                                     7
## Social interaction measurement                                    6
## Socioeconomic status                                              8
## Stimulus or stress design                                         4
## Timepoint                                                         5
## Treatment                                                         7
## Type I diabetes mellitus                                         10
## Vesicle membrane                                                  1
## Vitiligo                                                          4
## Abnormal stool composition                                        6
## Acute myeloid leukemia                                            4
## Alcohol use disorder measurement                                  4
## Arthritis                                                         6
## Asthma                                                           17
## Biological sex                                                    6
## Bipolar disorder                                                  5
## Celiac disease                                                    6
## Chlamydia trachomatis                                             2
## Colon carcinoma                                                   8
## Colorectal adenoma                                               10
## Contraception                                                     5
## COVID-19 symptoms measurement                                     5
## Diabetes mellitus                                                 9
## Diet measurement                                                  8
## Disease progression measurement                                   5
## Exposure                                                          4
## Gastric adenocarcinoma                                            8
## Glioma                                                            5
## Head and neck squamous cell carcinoma                             8
## Health study participation                                       36
## HIV mother to child transmission                                  8
## HIV-1 infection                                                   3
## Hydroxyproline measurement                                        3
## Hypertension, pregnancy-induced                                   6
## Hypoxia                                                           0
## Ischemic stroke                                                   5
## Lactose intolerance                                               5
## Lung transplantation                                              2
## Metabolic process                                                 7
## Neurodevelopmental delay                                          6
## Obsessive-compulsive disorder                                     5
## Oral lichen planus                                                4
## Oral mucositis                                                    3
## Oxalate measurement                                               8
## Postpartum                                                        5
## Psoriasis vulgaris                                               14
## Response to diet                                                 46
## Response to dietary antigen                                       6
## Response to ketogenic diet                                        3
## Rheumatoid arthritis                                             16
## Sample collection protocol                                        9
## SARS coronavirus                                                  6
## Social deprivation,Psychological measurement                     12
## Transplant outcome measurement                                   11
## Type II diabetes mellitus                                        42
## Vaginal microbiome measurement                                    5
## Viral load                                                        6
## Waist circumference                                               5
tabDiv(exps, "Shannon", "Condition", perc = TRUE)
##                                                           increased decreased
## Pulmonary tuberculosis                                        0.082     0.510
## Polycystic ovary syndrome                                     0.075     0.360
## Gastric cancer                                                0.110     0.380
## COVID-19                                                      0.130     0.280
## Periodontitis                                                 0.460     0.086
## Diet                                                          0.140     0.230
## HIV infection                                                 0.025     0.300
## Ulcerative colitis                                            0.056     0.670
## Clostridium difficile infection                               0.910     0.000
## Crohn's disease                                               0.000     0.480
## Multiple sclerosis                                            0.043     0.260
## Obesity                                                       0.076     0.180
## Systemic inflammatory response syndrome                       0.210     0.620
## Alzheimer's disease                                           0.047     0.260
## Chronic constipation                                          0.430     0.000
## Human papilloma virus infection                               0.260     0.026
## Gingivitis                                                    0.045     0.410
## Pancreatic carcinoma                                          0.560     0.062
## Smoking behaviour measurement                                 0.470     0.000
## Age                                                           0.190     0.420
## Dry eye syndrome                                              0.043     0.350
## Heart failure                                                 0.000     0.780
## Lung cancer                                                   0.110     0.470
## Mycobacterium tuberculosis                                    0.580     0.000
## Atopic eczema                                                 0.057     0.120
## Autism spectrum disorder                                      0.350     0.050
## Cesarean section                                              0.270     0.000
## Graves disease                                                0.067     0.470
## Parkinson's disease                                           0.160     0.110
## Response to allogeneic hematopoietic stem cell transplant     0.000     1.000
## Spontaneous preterm birth                                     0.500     0.270
## Acute pancreatitis                                            0.000     0.620
## Aging                                                         0.180     0.640
## Bronchiectasis                                                0.000     1.000
## Cervical cancer                                               0.450     0.000
## Constipation                                                  0.330     0.120
## Epilepsy                                                      0.500     0.000
## Helminthiasis                                                 0.380     0.000
## Oxygen                                                        1.000     0.000
## Response to antibiotic                                        0.062     0.220
## Species design                                                0.240     0.370
## Urinary tract infection                                       0.056     0.330
## Acute lymphoblastic leukemia                                  0.000     0.290
## Body mass index                                               0.000     0.570
## Chronic kidney disease                                        0.110     0.320
## Colitis                                                       0.670     0.000
## Colorectal cancer                                             0.170     0.130
## Cystic fibrosis                                               0.000     0.570
## Ethnic group                                                  0.190     0.440
## Food allergy                                                  0.220     0.074
## Gestational diabetes                                          0.100     0.000
## Hepatocellular carcinoma                                      0.210     0.420
## Human immunodeficiency virus                                  0.000     0.400
## Inflammatory bowel disease                                    0.000     0.800
## Pregnancy                                                     0.360     0.000
## Alcohol drinking                                              0.600     0.000
## Antimicrobial agent                                           0.170     0.240
## Atopic asthma                                                 0.330     0.083
## Birth measurement                                             0.430     0.000
## Chronic periodontitis                                         0.270     0.000
## Cognitive impairment                                          0.050     0.200
## Environmental exposure measurement                            0.430     0.000
## Extraction protocol                                           0.330     0.370
## Hematopoietic stem cell                                       0.000     0.500
## High fat diet                                                 0.570     0.140
## Hypertension                                                  0.370     0.210
## Hypothyroidism                                                0.000     0.430
## Male homosexuality                                            0.330     0.000
## Peri-Implantitis                                              0.600     0.000
## Response to antiviral drug                                    0.083     0.210
## SARS-CoV-2-related disease                                    0.000     0.380
## Schizophrenia                                                 0.034     0.140
## Smoking behavior                                              0.230     0.300
## Traditional Chinese medicine type                             0.130     0.330
## Tuberculosis                                                  0.290     0.710
## Acne                                                          0.000     0.400
## Age at assessment                                             0.600     0.200
## Breed                                                         0.000     0.220
## Cervical glandular intraepithelial neoplasia                  0.180     0.000
## Chronic obstructive pulmonary disease                         0.360     0.180
## Compound based treatment                                      0.000     0.400
## Dental caries                                                 0.330     0.000
## Eczema                                                        0.000     0.170
## Endometrial cancer                                            0.440     0.220
## Environmental factor                                          0.230     0.170
## Esophageal adenocarcinoma                                     0.000     0.330
## Iron biomarker measurement                                    0.170     0.500
## Irritable bowel syndrome                                      0.120     0.180
## Lifestyle measurement                                         0.200     0.100
## Milk allergic reaction                                        0.290     0.000
## Non-alcoholic fatty liver disease                             0.230     0.077
## Papillary thyroid carcinoma                                   0.170     0.000
## Phenotype                                                     0.095     0.000
## Phenylketonuria                                               0.120     0.380
## Population                                                    0.120     0.180
## Reproductive behaviour measurement                            0.400     0.000
## Response to anti-tuberculosis drug                            0.260     0.320
## Response to immunochemotherapy                                0.430     0.140
## Response to opioid                                            0.500     0.170
## Response to transplant                                        0.190     0.150
## Sampling site                                                 0.270     0.091
## Simian immunodeficiency virus infection                       0.000     0.180
## Sleep duration                                                0.500     0.170
## Small for gestational age                                     0.000     0.250
## Smoking status measurement                                    0.330     0.000
## Squamous cell carcinoma                                       0.330     0.000
## Streptococcus pneumoniae                                      0.000     0.330
## Stroke                                                        0.110     0.000
## Acute respiratory failure                                     0.550     0.450
## Age-related macular degeneration                              0.000     0.200
## Air pollution                                                 0.440     0.380
## Anxiety disorder                                              0.000     0.120
## Attention deficit-hyperactivity disorder                      0.220     0.110
## Breast cancer                                                 0.100     0.120
## Breastfeeding duration                                        0.200     0.300
## Chronic fatigue syndrome                                      0.000     0.200
## Chronic hepatitis B virus infection                           0.000     0.170
## Clinical treatment                                            0.120     0.250
## Coccidiosis                                                   0.000     0.200
## Delivery method                                               0.150     0.200
## Depressive disorder                                           0.091     0.180
## Diarrhea                                                      0.210     0.290
## Endometriosis                                                 0.110     0.160
## Esophageal cancer                                             0.200     0.400
## Esophageal squamous cell carcinoma                            0.170     0.000
## Estradiol measurement                                         0.200     0.400
## Fasting                                                       0.000     0.200
## Female infertility                                            0.330     0.170
## Fungal infectious disease                                     0.290     0.140
## Glaucoma                                                      0.270     0.330
## Hypertrophy                                                   0.200     0.000
## Infant                                                        0.200     0.000
## Major depressive disorder                                     0.000     0.140
## Metastatic colorectal cancer                                  0.170     0.330
## Myocardial infarction                                         0.042     0.083
## Non-alcoholic steatohepatitis                                 0.091     0.180
## Obstructive sleep apnea                                       0.000     0.083
## Oral cavity carcinoma                                         0.000     0.120
## Oral squamous cell carcinoma                                  0.380     0.250
## Ovarian cancer                                                0.095     0.071
## Pneumonia                                                     0.170     0.330
## Prediabetes syndrome                                          0.000     0.200
## Premature birth                                               0.140     0.000
## Prostate cancer                                               0.000     0.100
## Psoriasis                                                     0.067     0.000
## Respiratory Syncytial Virus Infection                         0.000     0.170
## Respiratory tract infectious disease                          0.000     0.170
## Response to stress                                            0.100     0.000
## Response to vaccine                                           0.120     0.250
## Sample treatment protocol                                     0.200     0.000
## Sampling time                                                 0.290     0.210
## Social interaction measurement                                0.220     0.110
## Socioeconomic status                                          0.200     0.270
## Stimulus or stress design                                     0.000     0.200
## Timepoint                                                     0.170     0.000
## Treatment                                                     0.290     0.210
## Type I diabetes mellitus                                      0.000     0.091
## Vesicle membrane                                              0.500     0.330
## Vitiligo                                                      0.000     0.200
## Abnormal stool composition                                    0.000     0.000
## Acute myeloid leukemia                                        0.170     0.170
## Alcohol use disorder measurement                              0.250     0.250
## Arthritis                                                     0.000     0.000
## Asthma                                                        0.130     0.130
## Biological sex                                                0.120     0.120
## Bipolar disorder                                              0.000     0.000
## Celiac disease                                                0.000     0.000
## Chlamydia trachomatis                                         0.330     0.330
## Colon carcinoma                                               0.000     0.000
## Colorectal adenoma                                            0.140     0.140
## Contraception                                                 0.000     0.000
## COVID-19 symptoms measurement                                 0.000     0.000
## Diabetes mellitus                                             0.091     0.091
## Diet measurement                                              0.000     0.000
## Disease progression measurement                               0.000     0.000
## Exposure                                                      0.170     0.170
## Gastric adenocarcinoma                                        0.000     0.000
## Glioma                                                        0.000     0.000
## Head and neck squamous cell carcinoma                         0.000     0.000
## Health study participation                                    0.071     0.071
## HIV mother to child transmission                              0.000     0.000
## HIV-1 infection                                               0.200     0.200
## Hydroxyproline measurement                                    0.200     0.200
## Hypertension, pregnancy-induced                               0.000     0.000
## Hypoxia                                                       0.500     0.500
## Ischemic stroke                                               0.000     0.000
## Lactose intolerance                                           0.000     0.000
## Lung transplantation                                          0.330     0.330
## Metabolic process                                             0.000     0.000
## Neurodevelopmental delay                                      0.000     0.000
## Obsessive-compulsive disorder                                 0.000     0.000
## Oral lichen planus                                            0.300     0.300
## Oral mucositis                                                0.290     0.290
## Oxalate measurement                                           0.100     0.100
## Postpartum                                                    0.000     0.000
## Psoriasis vulgaris                                            0.000     0.000
## Response to diet                                              0.089     0.089
## Response to dietary antigen                                   0.000     0.000
## Response to ketogenic diet                                    0.290     0.290
## Rheumatoid arthritis                                          0.190     0.190
## Sample collection protocol                                    0.000     0.000
## SARS coronavirus                                              0.000     0.000
## Social deprivation,Psychological measurement                  0.000     0.000
## Transplant outcome measurement                                0.000     0.000
## Type II diabetes mellitus                                     0.120     0.120
## Vaginal microbiome measurement                                0.000     0.000
## Viral load                                                    0.000     0.000
## Waist circumference                                           0.000     0.000
##                                                           unchanged
## Pulmonary tuberculosis                                        0.410
## Polycystic ovary syndrome                                     0.570
## Gastric cancer                                                0.510
## COVID-19                                                      0.590
## Periodontitis                                                 0.460
## Diet                                                          0.630
## HIV infection                                                 0.680
## Ulcerative colitis                                            0.280
## Clostridium difficile infection                               0.091
## Crohn's disease                                               0.520
## Multiple sclerosis                                            0.700
## Obesity                                                       0.740
## Systemic inflammatory response syndrome                       0.170
## Alzheimer's disease                                           0.700
## Chronic constipation                                          0.570
## Human papilloma virus infection                               0.720
## Gingivitis                                                    0.550
## Pancreatic carcinoma                                          0.380
## Smoking behaviour measurement                                 0.530
## Age                                                           0.390
## Dry eye syndrome                                              0.610
## Heart failure                                                 0.220
## Lung cancer                                                   0.420
## Mycobacterium tuberculosis                                    0.420
## Atopic eczema                                                 0.820
## Autism spectrum disorder                                      0.600
## Cesarean section                                              0.730
## Graves disease                                                0.470
## Parkinson's disease                                           0.740
## Response to allogeneic hematopoietic stem cell transplant     0.000
## Spontaneous preterm birth                                     0.230
## Acute pancreatitis                                            0.380
## Aging                                                         0.180
## Bronchiectasis                                                0.000
## Cervical cancer                                               0.550
## Constipation                                                  0.540
## Epilepsy                                                      0.500
## Helminthiasis                                                 0.620
## Oxygen                                                        0.000
## Response to antibiotic                                        0.720
## Species design                                                0.390
## Urinary tract infection                                       0.610
## Acute lymphoblastic leukemia                                  0.710
## Body mass index                                               0.430
## Chronic kidney disease                                        0.580
## Colitis                                                       0.330
## Colorectal cancer                                             0.690
## Cystic fibrosis                                               0.430
## Ethnic group                                                  0.380
## Food allergy                                                  0.700
## Gestational diabetes                                          0.900
## Hepatocellular carcinoma                                      0.370
## Human immunodeficiency virus                                  0.600
## Inflammatory bowel disease                                    0.200
## Pregnancy                                                     0.640
## Alcohol drinking                                              0.400
## Antimicrobial agent                                           0.600
## Atopic asthma                                                 0.580
## Birth measurement                                             0.570
## Chronic periodontitis                                         0.730
## Cognitive impairment                                          0.750
## Environmental exposure measurement                            0.570
## Extraction protocol                                           0.300
## Hematopoietic stem cell                                       0.500
## High fat diet                                                 0.290
## Hypertension                                                  0.420
## Hypothyroidism                                                0.570
## Male homosexuality                                            0.670
## Peri-Implantitis                                              0.400
## Response to antiviral drug                                    0.710
## SARS-CoV-2-related disease                                    0.620
## Schizophrenia                                                 0.830
## Smoking behavior                                              0.480
## Traditional Chinese medicine type                             0.530
## Tuberculosis                                                  0.000
## Acne                                                          0.600
## Age at assessment                                             0.200
## Breed                                                         0.780
## Cervical glandular intraepithelial neoplasia                  0.820
## Chronic obstructive pulmonary disease                         0.450
## Compound based treatment                                      0.600
## Dental caries                                                 0.670
## Eczema                                                        0.830
## Endometrial cancer                                            0.330
## Environmental factor                                          0.600
## Esophageal adenocarcinoma                                     0.670
## Iron biomarker measurement                                    0.330
## Irritable bowel syndrome                                      0.700
## Lifestyle measurement                                         0.700
## Milk allergic reaction                                        0.710
## Non-alcoholic fatty liver disease                             0.690
## Papillary thyroid carcinoma                                   0.830
## Phenotype                                                     0.900
## Phenylketonuria                                               0.500
## Population                                                    0.700
## Reproductive behaviour measurement                            0.600
## Response to anti-tuberculosis drug                            0.420
## Response to immunochemotherapy                                0.430
## Response to opioid                                            0.330
## Response to transplant                                        0.650
## Sampling site                                                 0.640
## Simian immunodeficiency virus infection                       0.820
## Sleep duration                                                0.330
## Small for gestational age                                     0.750
## Smoking status measurement                                    0.670
## Squamous cell carcinoma                                       0.670
## Streptococcus pneumoniae                                      0.670
## Stroke                                                        0.890
## Acute respiratory failure                                     0.000
## Age-related macular degeneration                              0.800
## Air pollution                                                 0.190
## Anxiety disorder                                              0.880
## Attention deficit-hyperactivity disorder                      0.670
## Breast cancer                                                 0.780
## Breastfeeding duration                                        0.500
## Chronic fatigue syndrome                                      0.800
## Chronic hepatitis B virus infection                           0.830
## Clinical treatment                                            0.620
## Coccidiosis                                                   0.800
## Delivery method                                               0.650
## Depressive disorder                                           0.730
## Diarrhea                                                      0.500
## Endometriosis                                                 0.740
## Esophageal cancer                                             0.400
## Esophageal squamous cell carcinoma                            0.830
## Estradiol measurement                                         0.400
## Fasting                                                       0.800
## Female infertility                                            0.500
## Fungal infectious disease                                     0.570
## Glaucoma                                                      0.400
## Hypertrophy                                                   0.800
## Infant                                                        0.800
## Major depressive disorder                                     0.860
## Metastatic colorectal cancer                                  0.500
## Myocardial infarction                                         0.880
## Non-alcoholic steatohepatitis                                 0.730
## Obstructive sleep apnea                                       0.920
## Oral cavity carcinoma                                         0.880
## Oral squamous cell carcinoma                                  0.380
## Ovarian cancer                                                0.830
## Pneumonia                                                     0.500
## Prediabetes syndrome                                          0.800
## Premature birth                                               0.860
## Prostate cancer                                               0.900
## Psoriasis                                                     0.930
## Respiratory Syncytial Virus Infection                         0.830
## Respiratory tract infectious disease                          0.830
## Response to stress                                            0.900
## Response to vaccine                                           0.620
## Sample treatment protocol                                     0.800
## Sampling time                                                 0.500
## Social interaction measurement                                0.670
## Socioeconomic status                                          0.530
## Stimulus or stress design                                     0.800
## Timepoint                                                     0.830
## Treatment                                                     0.500
## Type I diabetes mellitus                                      0.910
## Vesicle membrane                                              0.170
## Vitiligo                                                      0.800
## Abnormal stool composition                                    1.000
## Acute myeloid leukemia                                        0.670
## Alcohol use disorder measurement                              0.500
## Arthritis                                                     1.000
## Asthma                                                        0.740
## Biological sex                                                0.750
## Bipolar disorder                                              1.000
## Celiac disease                                                1.000
## Chlamydia trachomatis                                         0.330
## Colon carcinoma                                               1.000
## Colorectal adenoma                                            0.710
## Contraception                                                 1.000
## COVID-19 symptoms measurement                                 1.000
## Diabetes mellitus                                             0.820
## Diet measurement                                              1.000
## Disease progression measurement                               1.000
## Exposure                                                      0.670
## Gastric adenocarcinoma                                        1.000
## Glioma                                                        1.000
## Head and neck squamous cell carcinoma                         1.000
## Health study participation                                    0.860
## HIV mother to child transmission                              1.000
## HIV-1 infection                                               0.600
## Hydroxyproline measurement                                    0.600
## Hypertension, pregnancy-induced                               1.000
## Hypoxia                                                       0.000
## Ischemic stroke                                               1.000
## Lactose intolerance                                           1.000
## Lung transplantation                                          0.330
## Metabolic process                                             1.000
## Neurodevelopmental delay                                      1.000
## Obsessive-compulsive disorder                                 1.000
## Oral lichen planus                                            0.400
## Oral mucositis                                                0.430
## Oxalate measurement                                           0.800
## Postpartum                                                    1.000
## Psoriasis vulgaris                                            1.000
## Response to diet                                              0.820
## Response to dietary antigen                                   1.000
## Response to ketogenic diet                                    0.430
## Rheumatoid arthritis                                          0.620
## Sample collection protocol                                    1.000
## SARS coronavirus                                              1.000
## Social deprivation,Psychological measurement                  1.000
## Transplant outcome measurement                                1.000
## Type II diabetes mellitus                                     0.750
## Vaginal microbiome measurement                                1.000
## Viral load                                                    1.000
## Waist circumference                                           1.000
tabDiv(exps, "Richness", "Condition")
##                                                           increased decreased
## Diet                                                              6        20
## Helminthiasis                                                    13         0
## HIV infection                                                     3        15
## Multiple sclerosis                                                2        14
## Periodontitis                                                    15         3
## Polycystic ovary syndrome                                         5        16
## Pulmonary tuberculosis                                            6        16
## COVID-19                                                         11        20
## Parkinson's disease                                              19        27
## Phenotype                                                         9         1
## Small for gestational age                                         0         8
## Aging                                                             0         7
## Chronic constipation                                              7         0
## Gastric cancer                                                    5        12
## Gingivitis                                                        1         8
## Species design                                                   10        17
## Chronic kidney disease                                            0         6
## Increased intestinal transit time                                 6         0
## Response to allogeneic hematopoietic stem cell transplant         0         6
## Schizophrenia                                                     1         7
## Alcohol drinking                                                  5         0
## Antimicrobial agent                                               2         7
## Environmental factor                                              0         5
## Human immunodeficiency virus                                      1         6
## Human papilloma virus infection                                   7         2
## Acute lymphoblastic leukemia                                      5         1
## Air pollution                                                     9         5
## Cervical glandular intraepithelial neoplasia                      4         0
## Crohn's disease                                                   2         6
## Diarrhea                                                          5         1
## Dry eye syndrome                                                  0         4
## Epilepsy                                                          4         0
## Fungal infectious disease                                         0         4
## Major depressive disorder                                         4         0
## Stress-related disorder                                           0         4
## Ulcerative colitis                                                0         4
## Vesicle membrane                                                  5         1
## Alzheimer's disease                                               8         5
## Atopic asthma                                                     4         1
## Delivery method                                                   4         1
## Endometriosis                                                     4         1
## Food allergy                                                      0         3
## Graves disease                                                    2         5
## Hematopoietic stem cell                                           0         3
## Hypertension                                                      1         4
## Hypertrophy                                                       3         0
## Iron biomarker measurement                                        1         4
## Irritable bowel syndrome                                          4         7
## Oral squamous cell carcinoma                                      1         4
## Treatment                                                         4         7
## Treatment outcome measurement                                     1         4
## Tuberculosis                                                      2         5
## Alcohol use disorder measurement                                  2         0
## Bone mineral content measurement                                  0         2
## Breast cancer                                                     2         0
## Cognitive impairment                                              0         2
## Colorectal cancer                                                16        18
## Esophageal adenocarcinoma                                         0         2
## Gestational diabetes                                              4         6
## Health study participation                                        2         0
## Hypothyroidism                                                    0         2
## Inflammatory bowel disease                                        2         4
## Lung cancer                                                       0         2
## Metabolic process                                                 0         2
## Obesity                                                          10         8
## Phenylketonuria                                                   1         3
## Population                                                        2         0
## Response to antibiotic                                            0         2
## Response to antiviral drug                                        0         2
## Response to diet                                                  3         5
## Response to transplant                                            9         7
## Simian immunodeficiency virus infection                           0         2
## Smoking behavior                                                  6         8
## Smoking behaviour measurement                                     2         0
## Smoking status measurement                                        2         0
## Streptococcus pneumoniae                                          0         2
## Traditional Chinese medicine type                                 1         3
## Transplant outcome measurement                                    0         2
## Age                                                               4         5
## Asthma                                                            2         3
## Atopic eczema                                                     2         1
## Autism spectrum disorder                                          5         6
## Bone density                                                      0         1
## Breastfeeding duration                                            1         0
## Cesarean section                                                  3         2
## Coccidiosis                                                       0         1
## Colon carcinoma                                                   0         1
## Colorectal adenoma                                                1         2
## Endometrial cancer                                                1         2
## Heart failure                                                     2         3
## Infant                                                            1         0
## Ischemic stroke                                                   2         1
## Lifestyle measurement                                             3         2
## Neurodevelopmental delay                                          1         0
## Obsessive-compulsive disorder                                     0         1
## Ovarian cancer                                                    1         0
## Pregnancy                                                         1         0
## Psoriasis                                                         0         1
## Reproductive behaviour measurement                                1         0
## Response to stress                                                1         0
## Rheumatoid arthritis                                              3         4
## Sampling site                                                     1         2
## Socioeconomic status                                              2         1
## Transport                                                         1         2
## Type I diabetes mellitus                                          0         1
## Abnormal stool composition                                        0         0
## Attention deficit-hyperactivity disorder                          0         0
## Chlamydia trachomatis                                             1         1
## Chronic periodontitis                                             0         0
## Constipation                                                      7         7
## Depressive disorder                                               1         1
## Diabetes mellitus                                                 0         0
## Diet measurement                                                  0         0
## Ethnic group                                                      2         2
## Glioma                                                            1         1
## Head and neck squamous cell carcinoma                             0         0
## Hepatocellular carcinoma                                          3         3
## HIV mother to child transmission                                  0         0
## Male homosexuality                                                0         0
## Myocardial infarction                                             0         0
## Non-alcoholic fatty liver disease                                 0         0
## Papillary thyroid carcinoma                                       0         0
## Physical activity                                                 2         2
## Prostate cancer                                                   0         0
## Psoriasis vulgaris                                                0         0
## Sample collection protocol                                        0         0
## Stroke                                                            2         2
## Type II diabetes mellitus                                         4         4
## Urinary tract infection                                           1         1
## Viral load                                                        0         0
##                                                           unchanged
## Diet                                                             34
## Helminthiasis                                                     0
## HIV infection                                                    10
## Multiple sclerosis                                               29
## Periodontitis                                                    23
## Polycystic ovary syndrome                                        16
## Pulmonary tuberculosis                                            9
## COVID-19                                                         25
## Parkinson's disease                                              33
## Phenotype                                                        11
## Small for gestational age                                         0
## Aging                                                             1
## Chronic constipation                                              7
## Gastric cancer                                                   14
## Gingivitis                                                       14
## Species design                                                   14
## Chronic kidney disease                                            7
## Increased intestinal transit time                                 0
## Response to allogeneic hematopoietic stem cell transplant         0
## Schizophrenia                                                    14
## Alcohol drinking                                                  0
## Antimicrobial agent                                              10
## Environmental factor                                             17
## Human immunodeficiency virus                                      2
## Human papilloma virus infection                                  12
## Acute lymphoblastic leukemia                                      1
## Air pollution                                                     6
## Cervical glandular intraepithelial neoplasia                      2
## Crohn's disease                                                   4
## Diarrhea                                                          3
## Dry eye syndrome                                                  4
## Epilepsy                                                          3
## Fungal infectious disease                                         2
## Major depressive disorder                                         2
## Stress-related disorder                                           1
## Ulcerative colitis                                                2
## Vesicle membrane                                                  0
## Alzheimer's disease                                              28
## Atopic asthma                                                     7
## Delivery method                                                   9
## Endometriosis                                                     8
## Food allergy                                                      9
## Graves disease                                                    6
## Hematopoietic stem cell                                           3
## Hypertension                                                      8
## Hypertrophy                                                       2
## Iron biomarker measurement                                        1
## Irritable bowel syndrome                                         16
## Oral squamous cell carcinoma                                      0
## Treatment                                                         9
## Treatment outcome measurement                                     0
## Tuberculosis                                                      0
## Alcohol use disorder measurement                                  6
## Bone mineral content measurement                                  8
## Breast cancer                                                    17
## Cognitive impairment                                              9
## Colorectal cancer                                                22
## Esophageal adenocarcinoma                                         4
## Gestational diabetes                                             27
## Health study participation                                       29
## Hypothyroidism                                                    4
## Inflammatory bowel disease                                        1
## Lung cancer                                                      10
## Metabolic process                                                 5
## Obesity                                                          27
## Phenylketonuria                                                   4
## Population                                                        4
## Response to antibiotic                                            6
## Response to antiviral drug                                       13
## Response to diet                                                 16
## Response to transplant                                           14
## Simian immunodeficiency virus infection                           4
## Smoking behavior                                                  8
## Smoking behaviour measurement                                     5
## Smoking status measurement                                        5
## Streptococcus pneumoniae                                          3
## Traditional Chinese medicine type                                 4
## Transplant outcome measurement                                    5
## Age                                                               2
## Asthma                                                           13
## Atopic eczema                                                     6
## Autism spectrum disorder                                          0
## Bone density                                                      5
## Breastfeeding duration                                            5
## Cesarean section                                                 10
## Coccidiosis                                                       4
## Colon carcinoma                                                   9
## Colorectal adenoma                                               11
## Endometrial cancer                                                3
## Heart failure                                                     4
## Infant                                                            4
## Ischemic stroke                                                   3
## Lifestyle measurement                                             3
## Neurodevelopmental delay                                          5
## Obsessive-compulsive disorder                                     4
## Ovarian cancer                                                   39
## Pregnancy                                                         7
## Psoriasis                                                         8
## Reproductive behaviour measurement                                4
## Response to stress                                                9
## Rheumatoid arthritis                                              3
## Sampling site                                                     2
## Socioeconomic status                                              2
## Transport                                                         3
## Type I diabetes mellitus                                          4
## Abnormal stool composition                                        6
## Attention deficit-hyperactivity disorder                          5
## Chlamydia trachomatis                                             3
## Chronic periodontitis                                             6
## Constipation                                                     12
## Depressive disorder                                               5
## Diabetes mellitus                                                 5
## Diet measurement                                                  7
## Ethnic group                                                      1
## Glioma                                                            3
## Head and neck squamous cell carcinoma                            11
## Hepatocellular carcinoma                                          0
## HIV mother to child transmission                                  8
## Male homosexuality                                                9
## Myocardial infarction                                            19
## Non-alcoholic fatty liver disease                                 5
## Papillary thyroid carcinoma                                      12
## Physical activity                                                 1
## Prostate cancer                                                   7
## Psoriasis vulgaris                                               14
## Sample collection protocol                                        9
## Stroke                                                           17
## Type II diabetes mellitus                                        21
## Urinary tract infection                                           9
## Viral load                                                        5
tabDiv(exps, "Richness", "Condition", perc = TRUE)
##                                                           increased decreased
## Diet                                                          0.100     0.330
## Helminthiasis                                                 1.000     0.000
## HIV infection                                                 0.110     0.540
## Multiple sclerosis                                            0.044     0.310
## Periodontitis                                                 0.370     0.073
## Polycystic ovary syndrome                                     0.140     0.430
## Pulmonary tuberculosis                                        0.190     0.520
## COVID-19                                                      0.200     0.360
## Parkinson's disease                                           0.240     0.340
## Phenotype                                                     0.430     0.048
## Small for gestational age                                     0.000     1.000
## Aging                                                         0.000     0.880
## Chronic constipation                                          0.500     0.000
## Gastric cancer                                                0.160     0.390
## Gingivitis                                                    0.043     0.350
## Species design                                                0.240     0.410
## Chronic kidney disease                                        0.000     0.460
## Increased intestinal transit time                             1.000     0.000
## Response to allogeneic hematopoietic stem cell transplant     0.000     1.000
## Schizophrenia                                                 0.045     0.320
## Alcohol drinking                                              1.000     0.000
## Antimicrobial agent                                           0.110     0.370
## Environmental factor                                          0.000     0.230
## Human immunodeficiency virus                                  0.110     0.670
## Human papilloma virus infection                               0.330     0.095
## Acute lymphoblastic leukemia                                  0.710     0.140
## Air pollution                                                 0.450     0.250
## Cervical glandular intraepithelial neoplasia                  0.670     0.000
## Crohn's disease                                               0.170     0.500
## Diarrhea                                                      0.560     0.110
## Dry eye syndrome                                              0.000     0.500
## Epilepsy                                                      0.570     0.000
## Fungal infectious disease                                     0.000     0.670
## Major depressive disorder                                     0.670     0.000
## Stress-related disorder                                       0.000     0.800
## Ulcerative colitis                                            0.000     0.670
## Vesicle membrane                                              0.830     0.170
## Alzheimer's disease                                           0.200     0.120
## Atopic asthma                                                 0.330     0.083
## Delivery method                                               0.290     0.071
## Endometriosis                                                 0.310     0.077
## Food allergy                                                  0.000     0.250
## Graves disease                                                0.150     0.380
## Hematopoietic stem cell                                       0.000     0.500
## Hypertension                                                  0.077     0.310
## Hypertrophy                                                   0.600     0.000
## Iron biomarker measurement                                    0.170     0.670
## Irritable bowel syndrome                                      0.150     0.260
## Oral squamous cell carcinoma                                  0.200     0.800
## Treatment                                                     0.200     0.350
## Treatment outcome measurement                                 0.200     0.800
## Tuberculosis                                                  0.290     0.710
## Alcohol use disorder measurement                              0.250     0.000
## Bone mineral content measurement                              0.000     0.200
## Breast cancer                                                 0.110     0.000
## Cognitive impairment                                          0.000     0.180
## Colorectal cancer                                             0.290     0.320
## Esophageal adenocarcinoma                                     0.000     0.330
## Gestational diabetes                                          0.110     0.160
## Health study participation                                    0.065     0.000
## Hypothyroidism                                                0.000     0.330
## Inflammatory bowel disease                                    0.290     0.570
## Lung cancer                                                   0.000     0.170
## Metabolic process                                             0.000     0.290
## Obesity                                                       0.220     0.180
## Phenylketonuria                                               0.120     0.380
## Population                                                    0.330     0.000
## Response to antibiotic                                        0.000     0.250
## Response to antiviral drug                                    0.000     0.130
## Response to diet                                              0.120     0.210
## Response to transplant                                        0.300     0.230
## Simian immunodeficiency virus infection                       0.000     0.330
## Smoking behavior                                              0.270     0.360
## Smoking behaviour measurement                                 0.290     0.000
## Smoking status measurement                                    0.290     0.000
## Streptococcus pneumoniae                                      0.000     0.400
## Traditional Chinese medicine type                             0.120     0.380
## Transplant outcome measurement                                0.000     0.290
## Age                                                           0.360     0.450
## Asthma                                                        0.110     0.170
## Atopic eczema                                                 0.220     0.110
## Autism spectrum disorder                                      0.450     0.550
## Bone density                                                  0.000     0.170
## Breastfeeding duration                                        0.170     0.000
## Cesarean section                                              0.200     0.130
## Coccidiosis                                                   0.000     0.200
## Colon carcinoma                                               0.000     0.100
## Colorectal adenoma                                            0.071     0.140
## Endometrial cancer                                            0.170     0.330
## Heart failure                                                 0.220     0.330
## Infant                                                        0.200     0.000
## Ischemic stroke                                               0.330     0.170
## Lifestyle measurement                                         0.380     0.250
## Neurodevelopmental delay                                      0.170     0.000
## Obsessive-compulsive disorder                                 0.000     0.200
## Ovarian cancer                                                0.025     0.000
## Pregnancy                                                     0.120     0.000
## Psoriasis                                                     0.000     0.110
## Reproductive behaviour measurement                            0.200     0.000
## Response to stress                                            0.100     0.000
## Rheumatoid arthritis                                          0.300     0.400
## Sampling site                                                 0.200     0.400
## Socioeconomic status                                          0.400     0.200
## Transport                                                     0.170     0.330
## Type I diabetes mellitus                                      0.000     0.200
## Abnormal stool composition                                    0.000     0.000
## Attention deficit-hyperactivity disorder                      0.000     0.000
## Chlamydia trachomatis                                         0.200     0.200
## Chronic periodontitis                                         0.000     0.000
## Constipation                                                  0.270     0.270
## Depressive disorder                                           0.140     0.140
## Diabetes mellitus                                             0.000     0.000
## Diet measurement                                              0.000     0.000
## Ethnic group                                                  0.400     0.400
## Glioma                                                        0.200     0.200
## Head and neck squamous cell carcinoma                         0.000     0.000
## Hepatocellular carcinoma                                      0.500     0.500
## HIV mother to child transmission                              0.000     0.000
## Male homosexuality                                            0.000     0.000
## Myocardial infarction                                         0.000     0.000
## Non-alcoholic fatty liver disease                             0.000     0.000
## Papillary thyroid carcinoma                                   0.000     0.000
## Physical activity                                             0.400     0.400
## Prostate cancer                                               0.000     0.000
## Psoriasis vulgaris                                            0.000     0.000
## Sample collection protocol                                    0.000     0.000
## Stroke                                                        0.095     0.095
## Type II diabetes mellitus                                     0.140     0.140
## Urinary tract infection                                       0.091     0.091
## Viral load                                                    0.000     0.000
##                                                           unchanged
## Diet                                                           0.57
## Helminthiasis                                                  0.00
## HIV infection                                                  0.36
## Multiple sclerosis                                             0.64
## Periodontitis                                                  0.56
## Polycystic ovary syndrome                                      0.43
## Pulmonary tuberculosis                                         0.29
## COVID-19                                                       0.45
## Parkinson's disease                                            0.42
## Phenotype                                                      0.52
## Small for gestational age                                      0.00
## Aging                                                          0.12
## Chronic constipation                                           0.50
## Gastric cancer                                                 0.45
## Gingivitis                                                     0.61
## Species design                                                 0.34
## Chronic kidney disease                                         0.54
## Increased intestinal transit time                              0.00
## Response to allogeneic hematopoietic stem cell transplant      0.00
## Schizophrenia                                                  0.64
## Alcohol drinking                                               0.00
## Antimicrobial agent                                            0.53
## Environmental factor                                           0.77
## Human immunodeficiency virus                                   0.22
## Human papilloma virus infection                                0.57
## Acute lymphoblastic leukemia                                   0.14
## Air pollution                                                  0.30
## Cervical glandular intraepithelial neoplasia                   0.33
## Crohn's disease                                                0.33
## Diarrhea                                                       0.33
## Dry eye syndrome                                               0.50
## Epilepsy                                                       0.43
## Fungal infectious disease                                      0.33
## Major depressive disorder                                      0.33
## Stress-related disorder                                        0.20
## Ulcerative colitis                                             0.33
## Vesicle membrane                                               0.00
## Alzheimer's disease                                            0.68
## Atopic asthma                                                  0.58
## Delivery method                                                0.64
## Endometriosis                                                  0.62
## Food allergy                                                   0.75
## Graves disease                                                 0.46
## Hematopoietic stem cell                                        0.50
## Hypertension                                                   0.62
## Hypertrophy                                                    0.40
## Iron biomarker measurement                                     0.17
## Irritable bowel syndrome                                       0.59
## Oral squamous cell carcinoma                                   0.00
## Treatment                                                      0.45
## Treatment outcome measurement                                  0.00
## Tuberculosis                                                   0.00
## Alcohol use disorder measurement                               0.75
## Bone mineral content measurement                               0.80
## Breast cancer                                                  0.89
## Cognitive impairment                                           0.82
## Colorectal cancer                                              0.39
## Esophageal adenocarcinoma                                      0.67
## Gestational diabetes                                           0.73
## Health study participation                                     0.94
## Hypothyroidism                                                 0.67
## Inflammatory bowel disease                                     0.14
## Lung cancer                                                    0.83
## Metabolic process                                              0.71
## Obesity                                                        0.60
## Phenylketonuria                                                0.50
## Population                                                     0.67
## Response to antibiotic                                         0.75
## Response to antiviral drug                                     0.87
## Response to diet                                               0.67
## Response to transplant                                         0.47
## Simian immunodeficiency virus infection                        0.67
## Smoking behavior                                               0.36
## Smoking behaviour measurement                                  0.71
## Smoking status measurement                                     0.71
## Streptococcus pneumoniae                                       0.60
## Traditional Chinese medicine type                              0.50
## Transplant outcome measurement                                 0.71
## Age                                                            0.18
## Asthma                                                         0.72
## Atopic eczema                                                  0.67
## Autism spectrum disorder                                       0.00
## Bone density                                                   0.83
## Breastfeeding duration                                         0.83
## Cesarean section                                               0.67
## Coccidiosis                                                    0.80
## Colon carcinoma                                                0.90
## Colorectal adenoma                                             0.79
## Endometrial cancer                                             0.50
## Heart failure                                                  0.44
## Infant                                                         0.80
## Ischemic stroke                                                0.50
## Lifestyle measurement                                          0.38
## Neurodevelopmental delay                                       0.83
## Obsessive-compulsive disorder                                  0.80
## Ovarian cancer                                                 0.98
## Pregnancy                                                      0.88
## Psoriasis                                                      0.89
## Reproductive behaviour measurement                             0.80
## Response to stress                                             0.90
## Rheumatoid arthritis                                           0.30
## Sampling site                                                  0.40
## Socioeconomic status                                           0.40
## Transport                                                      0.50
## Type I diabetes mellitus                                       0.80
## Abnormal stool composition                                     1.00
## Attention deficit-hyperactivity disorder                       1.00
## Chlamydia trachomatis                                          0.60
## Chronic periodontitis                                          1.00
## Constipation                                                   0.46
## Depressive disorder                                            0.71
## Diabetes mellitus                                              1.00
## Diet measurement                                               1.00
## Ethnic group                                                   0.20
## Glioma                                                         0.60
## Head and neck squamous cell carcinoma                          1.00
## Hepatocellular carcinoma                                       0.00
## HIV mother to child transmission                               1.00
## Male homosexuality                                             1.00
## Myocardial infarction                                          1.00
## Non-alcoholic fatty liver disease                              1.00
## Papillary thyroid carcinoma                                    1.00
## Physical activity                                              0.20
## Prostate cancer                                                1.00
## Psoriasis vulgaris                                             1.00
## Sample collection protocol                                     1.00
## Stroke                                                         0.81
## Type II diabetes mellitus                                      0.72
## Urinary tract infection                                        0.82
## Viral load                                                     1.00

Body sites with consistently increased or decreased alpha diversity:

tabDiv(exps, "Shannon", "Body site")
##                                                 increased decreased unchanged
## Feces                                                 372       558      1611
## Sputum                                                  7        23        16
## Vagina                                                 22         9        41
## Blood serum                                             9         0         0
## Oral cavity                                            15         6        25
## Posterior fornix of vagina                              9         0         9
## Buccal mucosa                                          11         3         9
## Saliva                                                 41        49       198
## Stomach                                                 6        14         5
## Uterine cervix                                          9         1        20
## Uterine cervix,Vaginal fluid                            9         1         0
## Skin of body                                            8        15         8
## Supragingival dental plaque                             3        10        14
## Ileum                                                   3         9        13
## Pharynx                                                 6         1         2
## Space surrounding organism                              2         7        13
## Tongue                                                  0         5        16
## Axilla skin                                             5         1        11
## Caecum                                                  4         8        33
## Rectum                                                  3         7        20
## Throat                                                  0         4        11
## Ascending colon                                         3         0         6
## Ascending colon,Colorectal mucosa,Sigmoid colon         3         0         2
## Colorectal mucosa                                       0         3         9
## Duodenum                                                0         3         6
## Intestine                                               1         4        19
## Lung                                                    4         7        13
## Meconium                                                5         2        14
## Skin of forearm                                         3         0         3
## Sputum,Feces                                            1         4         1
## Urine                                                   4         1        20
## Bile                                                    2         0         3
## Blood                                                   1         3        15
## Brachialis muscle                                       0         2         3
## Cecum mucosa                                            2         4         6
## Conjunctiva                                             1         3        12
## Conjunctival sac                                        1         3         3
## Esophagus                                               0         2         4
## Forelimb skin                                           2         0         4
## Mouth                                                   8         6        28
## Oropharynx                                              1         3         5
## Thyroid gland                                           2         0        10
## Uterus                                                  3         1        11
## Body proper,Insect leg                                  0         1         5
## Breast                                                  3         4        10
## Breast,Milk                                             1         0         4
## Bulbar conjunctiva                                      3         2         5
## Colon                                                   6         5        20
## Dental plaque                                           4         3         5
## Digestive tract                                         2         1         2
## Gingival groove                                         2         1         6
## Liver                                                   5         4         0
## Milk                                                    0         1        11
## Mucosa of stomach                                       1         0         4
## Rumen                                                   2         1         4
## Small intestine                                         3         4         1
## Subgingival dental plaque                              13        14        37
## Vagina,Uterine cervix                                   3         2         7
## Vaginal fluid                                           1         2         8
## Bronchus                                                0         0         6
## Endothelium of trachea                                  3         3         0
## Internal cheek pouch                                    0         0        11
## Jejunum                                                 1         1         8
## Nasal cavity                                            1         1         5
## Nasopharynx                                             6         6        39
## Ovary                                                   0         0         7
## Peritoneal fluid                                        0         0         6
## Posterior wall of oropharynx                            2         2         1
## Skin epidermis                                          2         2         4
## Skin of abdomen                                         0         0         5
## Surface of tongue                                       2         2         3
## Ventral side of post-anal tail                          0         0         6
tabDiv(exps, "Shannon", "Body site", perc = TRUE)
##                                                 increased decreased unchanged
## Feces                                               0.150     0.220      0.63
## Sputum                                              0.150     0.500      0.35
## Vagina                                              0.310     0.120      0.57
## Blood serum                                         1.000     0.000      0.00
## Oral cavity                                         0.330     0.130      0.54
## Posterior fornix of vagina                          0.500     0.000      0.50
## Buccal mucosa                                       0.480     0.130      0.39
## Saliva                                              0.140     0.170      0.69
## Stomach                                             0.240     0.560      0.20
## Uterine cervix                                      0.300     0.033      0.67
## Uterine cervix,Vaginal fluid                        0.900     0.100      0.00
## Skin of body                                        0.260     0.480      0.26
## Supragingival dental plaque                         0.110     0.370      0.52
## Ileum                                               0.120     0.360      0.52
## Pharynx                                             0.670     0.110      0.22
## Space surrounding organism                          0.091     0.320      0.59
## Tongue                                              0.000     0.240      0.76
## Axilla skin                                         0.290     0.059      0.65
## Caecum                                              0.089     0.180      0.73
## Rectum                                              0.100     0.230      0.67
## Throat                                              0.000     0.270      0.73
## Ascending colon                                     0.330     0.000      0.67
## Ascending colon,Colorectal mucosa,Sigmoid colon     0.600     0.000      0.40
## Colorectal mucosa                                   0.000     0.250      0.75
## Duodenum                                            0.000     0.330      0.67
## Intestine                                           0.042     0.170      0.79
## Lung                                                0.170     0.290      0.54
## Meconium                                            0.240     0.095      0.67
## Skin of forearm                                     0.500     0.000      0.50
## Sputum,Feces                                        0.170     0.670      0.17
## Urine                                               0.160     0.040      0.80
## Bile                                                0.400     0.000      0.60
## Blood                                               0.053     0.160      0.79
## Brachialis muscle                                   0.000     0.400      0.60
## Cecum mucosa                                        0.170     0.330      0.50
## Conjunctiva                                         0.062     0.190      0.75
## Conjunctival sac                                    0.140     0.430      0.43
## Esophagus                                           0.000     0.330      0.67
## Forelimb skin                                       0.330     0.000      0.67
## Mouth                                               0.190     0.140      0.67
## Oropharynx                                          0.110     0.330      0.56
## Thyroid gland                                       0.170     0.000      0.83
## Uterus                                              0.200     0.067      0.73
## Body proper,Insect leg                              0.000     0.170      0.83
## Breast                                              0.180     0.240      0.59
## Breast,Milk                                         0.200     0.000      0.80
## Bulbar conjunctiva                                  0.300     0.200      0.50
## Colon                                               0.190     0.160      0.65
## Dental plaque                                       0.330     0.250      0.42
## Digestive tract                                     0.400     0.200      0.40
## Gingival groove                                     0.220     0.110      0.67
## Liver                                               0.560     0.440      0.00
## Milk                                                0.000     0.083      0.92
## Mucosa of stomach                                   0.200     0.000      0.80
## Rumen                                               0.290     0.140      0.57
## Small intestine                                     0.380     0.500      0.12
## Subgingival dental plaque                           0.200     0.220      0.58
## Vagina,Uterine cervix                               0.250     0.170      0.58
## Vaginal fluid                                       0.091     0.180      0.73
## Bronchus                                            0.000     0.000      1.00
## Endothelium of trachea                              0.500     0.500      0.00
## Internal cheek pouch                                0.000     0.000      1.00
## Jejunum                                             0.100     0.100      0.80
## Nasal cavity                                        0.140     0.140      0.71
## Nasopharynx                                         0.120     0.120      0.76
## Ovary                                               0.000     0.000      1.00
## Peritoneal fluid                                    0.000     0.000      1.00
## Posterior wall of oropharynx                        0.400     0.400      0.20
## Skin epidermis                                      0.250     0.250      0.50
## Skin of abdomen                                     0.000     0.000      1.00
## Surface of tongue                                   0.290     0.290      0.43
## Ventral side of post-anal tail                      0.000     0.000      1.00
tabDiv(exps, "Richness", "Body site")
##                              increased decreased unchanged
## Feces                              231       352       839
## Oral cavity                         15         4        19
## Sputum                               0        11         5
## Supragingival dental plaque          0         9         9
## Ileum                                3        11        10
## Mucosa of rectum                     0         8         1
## Stomach                              4        12         3
## Mouth                               10         3         9
## Posterior fornix of vagina           8         1         2
## Uterine cervix                       8         1        11
## Oropharynx                           0         6         6
## Colon                                9         4        12
## Rectum                               1         6         8
## Skin epidermis                       0         5         2
## Skin of body                         4         9         6
## Uterine cervix,Vaginal fluid         7         2         1
## Conjunctival sac                     0         4         1
## Throat                               1         5         5
## Vagina                               6         2        17
## Ascending colon                      3         0         6
## Lung                                 0         3         3
## Small intestine                      1         4         0
## Subgingival dental plaque            9         6        35
## Cecum mucosa                         2         4         1
## Dental plaque                        1         3         5
## Ear                                  2         0         3
## Esophagus                            0         2         4
## Saliva                              25        27       107
## Surface of tongue                    4         2         1
## Tongue                               2         4         7
## Urine                                4         2        16
## Blood                                1         2         4
## Caecum                               5         6        12
## Intestine                            2         1        16
## Meconium                             2         3         7
## Nasal cavity                         1         2         6
## Nasopharynx                          8         9        25
## Rumen                                0         1         4
## Vagina,Uterine cervix                1         0        11
## Breast                               1         1         7
## Bronchus                             0         0         6
## Buccal mucosa                        2         2         6
## Conjunctiva                          1         1         5
## Internal cheek pouch                 0         0         7
## Liver                                3         3         0
## Milk                                 2         2         5
## Ovary                                0         0         7
## Peritoneal fluid                     0         0         6
## Thyroid gland                        0         0        12
tabDiv(exps, "Richness", "Body site", perc = TRUE)
##                              increased decreased unchanged
## Feces                            0.160     0.250      0.59
## Oral cavity                      0.390     0.110      0.50
## Sputum                           0.000     0.690      0.31
## Supragingival dental plaque      0.000     0.500      0.50
## Ileum                            0.120     0.460      0.42
## Mucosa of rectum                 0.000     0.890      0.11
## Stomach                          0.210     0.630      0.16
## Mouth                            0.450     0.140      0.41
## Posterior fornix of vagina       0.730     0.091      0.18
## Uterine cervix                   0.400     0.050      0.55
## Oropharynx                       0.000     0.500      0.50
## Colon                            0.360     0.160      0.48
## Rectum                           0.067     0.400      0.53
## Skin epidermis                   0.000     0.710      0.29
## Skin of body                     0.210     0.470      0.32
## Uterine cervix,Vaginal fluid     0.700     0.200      0.10
## Conjunctival sac                 0.000     0.800      0.20
## Throat                           0.091     0.450      0.45
## Vagina                           0.240     0.080      0.68
## Ascending colon                  0.330     0.000      0.67
## Lung                             0.000     0.500      0.50
## Small intestine                  0.200     0.800      0.00
## Subgingival dental plaque        0.180     0.120      0.70
## Cecum mucosa                     0.290     0.570      0.14
## Dental plaque                    0.110     0.330      0.56
## Ear                              0.400     0.000      0.60
## Esophagus                        0.000     0.330      0.67
## Saliva                           0.160     0.170      0.67
## Surface of tongue                0.570     0.290      0.14
## Tongue                           0.150     0.310      0.54
## Urine                            0.180     0.091      0.73
## Blood                            0.140     0.290      0.57
## Caecum                           0.220     0.260      0.52
## Intestine                        0.110     0.053      0.84
## Meconium                         0.170     0.250      0.58
## Nasal cavity                     0.110     0.220      0.67
## Nasopharynx                      0.190     0.210      0.60
## Rumen                            0.000     0.200      0.80
## Vagina,Uterine cervix            0.083     0.000      0.92
## Breast                           0.110     0.110      0.78
## Bronchus                         0.000     0.000      1.00
## Buccal mucosa                    0.200     0.200      0.60
## Conjunctiva                      0.140     0.140      0.71
## Internal cheek pouch             0.000     0.000      1.00
## Liver                            0.500     0.500      0.00
## Milk                             0.220     0.220      0.56
## Ovary                            0.000     0.000      1.00
## Peritoneal fluid                 0.000     0.000      1.00
## Thyroid gland                    0.000     0.000      1.00

Signature stats

sigs <- bugsigdbr::getSignatures(dat, tax.id.type = "metaphlan")

Unique microbes

Number unique microbes contained in the signatures:

(nuniq <- length(unique(unlist(sigs))))
## [1] 7934

Development of unique microbes captured over time:

Microbe set size distribution

##    Min. 1st Qu.  Median    Mean 3rd Qu.    Max. 
##   1.000   2.000   4.000   8.137  10.000 467.000
gghistogram(lengths(sigs), bins = 30, ylab = "number of signatures",
    xlab = "signature size", fill = "#00AFBB", ggtheme = theme_bw())

sum(lengths(sigs) > 4)
## [1] 6389

Microbe co-occurrence

dat.feces <- subset(dat, `Body site` == "Feces")
cooc.mat <- microbeHeatmap(dat.feces, tax.level = "genus", anno = "genus")
## Loading required namespace: safe

antag.mat <- microbeHeatmap(dat.feces, tax.level = "genus", anno = "genus", antagonistic = TRUE)

Get the top 20 genera most frequently reported as differentially abundant:

sigs.feces <- getSignatures(dat.feces, tax.id.type = "taxname", 
                            tax.level = "genus", exact.tax.level = FALSE) 
top20 <- sort(table(unlist(sigs.feces)), decreasing = TRUE)[1:20]
top20
## 
##      Bacteroides Faecalibacterium  Bifidobacterium          Blautia 
##              836              593              586              551 
##    Lactobacillus    Streptococcus     Ruminococcus       Prevotella 
##              519              508              484              482 
##      Clostridium        Roseburia  Parabacteroides        Alistipes 
##              477              477              436              405 
##      Akkermansia            Dorea      Coprococcus      Veillonella 
##              352              338              334              293 
##      Collinsella     Enterococcus     Anaerostipes       Sutterella 
##              290              289              287              276

Subset heatmaps to the top 20 genera most frequently reported as differentially abundant:

all(names(top20) %in% rownames(cooc.mat))
## [1] TRUE
cooc.mat <- cooc.mat[names(top20), names(top20)]
all(names(top20) %in% rownames(antag.mat))
## [1] TRUE
antag.mat <- antag.mat[names(top20), names(top20)]

Distinguish by direction of abundance change (increased / decreased):

# increased
sub.dat.feces <- subset(dat.feces, `Abundance in Group 1` == "increased")
sigs.feces.up <- getSignatures(sub.dat.feces, tax.id.type = "taxname", 
                               tax.level = "genus", exact.tax.level = FALSE) 
top20.up <- table(unlist(sigs.feces.up))[names(top20)]
top20.up
## 
##      Bacteroides Faecalibacterium  Bifidobacterium          Blautia 
##              414              204              316              260 
##    Lactobacillus    Streptococcus     Ruminococcus       Prevotella 
##              319              321              223              232 
##      Clostridium        Roseburia  Parabacteroides        Alistipes 
##              252              159              250              193 
##      Akkermansia            Dorea      Coprococcus      Veillonella 
##              232              143              140              171 
##      Collinsella     Enterococcus     Anaerostipes       Sutterella 
##              154              209              132              139
# decreased
sub.dat.feces <- subset(dat.feces, `Abundance in Group 1` == "decreased")
sigs.feces.down <- getSignatures(sub.dat.feces, tax.id.type = "taxname", 
                                 tax.level = "genus", exact.tax.level = FALSE) 
top20.down <- table(unlist(sigs.feces.down))[names(top20)]
top20.down
## 
##      Bacteroides Faecalibacterium  Bifidobacterium          Blautia 
##              417              385              265              287 
##    Lactobacillus    Streptococcus     Ruminococcus       Prevotella 
##              198              182              257              247 
##      Clostridium        Roseburia  Parabacteroides        Alistipes 
##              220              314              182              208 
##      Akkermansia            Dorea      Coprococcus      Veillonella 
##              117              191              190              119 
##      Collinsella     Enterococcus     Anaerostipes       Sutterella 
##              132               78              151              137

Plot the heatmap

# annotation
mat <- matrix(nc = 2, cbind(top20.up, top20.down))
bp <- ComplexHeatmap::anno_barplot(mat, gp = gpar(fill = c("#D55E00", "#0072B2"),
                                                  col = c("#D55E00", "#0072B2")),
                                   height = unit(2, "cm"))
banno <- ComplexHeatmap::HeatmapAnnotation(`Abundance in Group 1` = bp)

lgd_list <- list(
    Legend(labels = c("increased", "decreased"), 
           title = "Abundance in Group 1", 
           type = "grid",
           legend_gp = gpar(col = c("#D55E00", "#0072B2"), fill = c("#D55E00", "#0072B2"))))
                                            
# same direction
# lcm <- sweep(cooc.mat, 2, matrixStats::colMaxs(cooc.mat), FUN = "/")
# we need to dampen the maximum here a bit down,
# otherwise 100% self co-occurrence takes up a large fraction of the colorscale,
sec <- apply(cooc.mat, 2, function(x) sort(x, decreasing = TRUE)[2])
cooc.mat2 <- cooc.mat
for(i in 1:ncol(cooc.mat2)) cooc.mat2[i,i] <- min(cooc.mat2[i,i], 1.4 * sec[i])
lcm <- sweep(cooc.mat2, 2, matrixStats::colMaxs(cooc.mat2), FUN = "/")
col <- circlize::colorRamp2(c(0,1), c("#EEEEEE", "red"))
ht1 <- ComplexHeatmap::Heatmap(lcm,
                               col = col, 
                               name = "Relative frequency (top)",
                               cluster_columns = FALSE, 
                               row_km = 3, 
                               row_title = "same direction", 
                               column_names_rot = 45,
                               row_names_gp = gpar(fontsize = 8),
                               column_names_gp = gpar(fontsize = 8))

# opposite direction
acm <- sweep(antag.mat, 2, matrixStats::colMaxs(antag.mat), FUN = "/")
col <- circlize::colorRamp2(c(0,1), c("#EEEEEE", "blue"))
ht2 <- ComplexHeatmap::Heatmap(acm,
                               col = col, 
                               name = "Relative frequency (bottom)",
                               cluster_columns = FALSE, 
                               row_title = "opposite direction", 
                               row_km = 3, 
                               column_names_rot = 45,
                               row_names_gp = gpar(fontsize = 8),
                               column_names_gp = gpar(fontsize = 8))

# phylum
sfp <- bugsigdbr::getSignatures(dat.feces, tax.id.type = "metaphlan", 
                                tax.level = "genus", exact.tax.level = FALSE) 
sfp20 <- sort(table(unlist(sfp)), decreasing = TRUE)[1:20]
uanno <- bugsigdbr::extractTaxLevel(names(sfp20),
                                    tax.id.type = "taxname",
                                    tax.level = "mixed",
                                    exact.tax.level = FALSE) 
phyla.grid <- seq_along(unique(uanno))
panno <- ComplexHeatmap::HeatmapAnnotation(phylum = uanno)

uanno <- matrix(uanno, nrow = 1)
colnames(uanno) <- names(top20)
pcols <- c("#CC79A7", "#F0E442", "#009E73", "#56B4E9", "#E69F00")
uanno <- ComplexHeatmap::Heatmap(uanno, name = "Phylum",
                                 col = pcols[phyla.grid],
                                 cluster_columns = FALSE,
                                 column_names_rot = 45,
                                 column_names_gp = gpar(fontsize = 8))
## There are 20 unique colors in the vector `col` and 20 unique values in
## `matrix`. `Heatmap()` will treat it as an exact discrete one-to-one
## mapping. If this is not what you want, slightly change the number of
## colors, e.g. by adding one more color or removing a color.
# put everything together
ht_list <- ht1 %v% banno %v% ht2 %v% uanno
ComplexHeatmap::draw(ht_list, annotation_legend_list = lgd_list, merge_legend = TRUE)

decorate_annotation("Abundance in Group 1", {
    grid.text("# signatures", x = unit(-1, "cm"), rot = 90, just = "bottom", gp = gpar(fontsize = 8))
    grid.text("*", x = unit(2.45, "cm"), y = unit(1.2, "cm"))
    grid.text("*", x = unit(5.18, "cm"), y = unit(1, "cm"))
    grid.text("*", x = unit(6.55, "cm"), y = unit(0.95, "cm"))
    grid.text("*", x = unit(8.6, "cm"), y = unit(0.85, "cm"))
    grid.text("*", x = unit(10, "cm"), y = unit(0.7, "cm"))
    grid.text("*", x = unit(10.7, "cm"), y = unit(0.7, "cm"))
})

Signature similarity

Jaccard index

Inspect signature similarity for signatures from stomach samples based on Jaccard index:

stomachsub <- subset(dat, `Body site` == "Stomach")
sigsub <- bugsigdbr::getSignatures(stomachsub)
pair.jsim <- calcJaccardSimilarity(sigsub)

Create a dendrogram of Jaccard dissimilarities (1.0 has no overlap, 0.0 are identical signatures).

jdist <- as.dist(1 - pair.jsim)
plot(hclust(jdist))