{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,4,21]],"date-time":"2026-04-21T17:42:23Z","timestamp":1776793343315,"version":"3.51.2"},"reference-count":60,"publisher":"Oxford University Press (OUP)","issue":"6","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2010,3,15]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>Motivation: Metagenomics is the study of genetic material recovered directly from environmental samples. Taxonomic and functional differences between metagenomic samples can highlight the influence of ecological factors on patterns of microbial life in a wide range of habitats. Statistical hypothesis tests can help us distinguish ecological influences from sampling artifacts, but knowledge of only the P-value from a statistical hypothesis test is insufficient to make inferences about biological relevance. Current reporting practices for pairwise comparative metagenomics are inadequate, and better tools are needed for comparative metagenomic analysis.<\/jats:p>\n                  <jats:p>Results: We have developed a new software package, STAMP, for comparative metagenomics that supports best practices in analysis and reporting. Examination of a pair of iron mine metagenomes demonstrates that deeper biological insights can be gained using statistical techniques available in our software. An analysis of the functional potential of \u2018Candidatus Accumulibacter phosphatis\u2019 in two enhanced biological phosphorus removal metagenomes identified several subsystems that differ between the A.phosphatis stains in these related communities, including phosphate metabolism, secretion and metal transport.<\/jats:p>\n                  <jats:p>Availability: Python source code and binaries are freely available from our website at http:\/\/kiwi.cs.dal.ca\/Software\/STAMP<\/jats:p>\n                  <jats:p>Contact: \u00a0beiko@cs.dal.ca<\/jats:p>\n                  <jats:p>Supplementary information: \u00a0Supplementary data are available at Bioinformatics online.<\/jats:p>","DOI":"10.1093\/bioinformatics\/btq041","type":"journal-article","created":{"date-parts":[[2010,2,3]],"date-time":"2010-02-03T20:55:22Z","timestamp":1265230522000},"page":"715-721","source":"Crossref","is-referenced-by-count":820,"title":["Identifying biologically relevant differences between metagenomic communities"],"prefix":"10.1093","volume":"26","author":[{"given":"Donovan H.","family":"Parks","sequence":"first","affiliation":[{"name":"Faculty of Computer Science, Dalhousie University, 6050 University Avenue, Halifax, Nova Scotia, Canada B3H 1W5"}]},{"given":"Robert G.","family":"Beiko","sequence":"additional","affiliation":[{"name":"Faculty of Computer Science, Dalhousie University, 6050 University Avenue, Halifax, Nova Scotia, Canada B3H 1W5"}]}],"member":"286","published-online":{"date-parts":[[2010,2,3]]},"reference":[{"key":"2023012508001908600_B1","volume-title":"Encyclopedia of Measurement and Statistics.","author":"Abdi","year":"2007"},{"key":"2023012508001908600_B2","doi-asserted-by":"crossref","first-page":"1612","DOI":"10.1542\/peds.2005-2269","article-title":"Inappropriate interpretation of the odds ratio: oddly not that uncommon","volume":"116","author":"Agrawal","year":"2005","journal-title":"Pediatrics"},{"key":"2023012508001908600_B3","volume-title":"Categorical Data Analysis.","author":"Agresti","year":"1990"},{"key":"2023012508001908600_B4","first-page":"131","article-title":"A survey of exact inference for contingency tables","volume":"7","author":"Agresti","year":"1992","journal-title":"Stat. Sci."},{"key":"2023012508001908600_B5","doi-asserted-by":"crossref","first-page":"597","DOI":"10.1111\/j.0006-341X.1999.00597.x","article-title":"On logit confidence intervals for the odds ratio with small samples","volume":"55","author":"Agresti","year":"1999","journal-title":"Biometrics"},{"key":"2023012508001908600_B6","doi-asserted-by":"crossref","first-page":"1012","DOI":"10.1038\/ismej.2009.45","article-title":"The genome sequence of the psychrophilic archaeon, Methanococcoides burtonii: the role of genome evolution in cold adaptation","volume":"3","author":"Allen","year":"2009","journal-title":"ISME J."},{"key":"2023012508001908600_B7","first-page":"123","article-title":"Significance tests for 2 x 2 tables","volume":"34","author":"Barnard","year":"1947","journal-title":"Biometrika"},{"key":"2023012508001908600_B8","doi-asserted-by":"crossref","first-page":"1469","DOI":"10.1002\/sim.4780081206","article-title":"On alleged gains in power from lower P-values","volume":"8","author":"Barnard","year":"1989","journal-title":"Stat. Med."},{"key":"2023012508001908600_B9","doi-asserted-by":"crossref","first-page":"1468","DOI":"10.1136\/bmj.320.7247.1468","article-title":"The odds ratio","volume":"320","author":"Bland","year":"2000","journal-title":"BMJ"},{"key":"2023012508001908600_B10","doi-asserted-by":"crossref","first-page":"1902","DOI":"10.1126\/science.289.5486.1902","article-title":"Bacterial rhodopsin: evidence for a new type of phototrophy in the sea","volume":"289","author":"B\u00e9j\u00e0","year":"2000","journal-title":"Science"},{"key":"2023012508001908600_B11","doi-asserted-by":"crossref","first-page":"289","DOI":"10.1111\/j.2517-6161.1995.tb02031.x","article-title":"Controlling the false discovery rate: a practical and powerful approach to multiple testing","volume":"57","author":"Benjamini","year":"1995","journal-title":"J. Royal Stat. Soc. B"},{"key":"2023012508001908600_B12","doi-asserted-by":"crossref","first-page":"1948","DOI":"10.1073\/pnas.0806191105","article-title":"Gene-centric metagenomics of the fiber-adherent bovine rumen microbiome reveals forage specific glycoside hydrolases","volume":"106","author":"Brulc","year":"2009","journal-title":"Proc. Natl Acad. Sci. USA"},{"key":"2023012508001908600_B13","doi-asserted-by":"crossref","first-page":"315","DOI":"10.1214\/aoms\/1177729380","article-title":"The chi-square test of goodness of fit","volume":"23","author":"Cochran","year":"1952","journal-title":"Ann. Math. Stat."},{"key":"2023012508001908600_B14","doi-asserted-by":"crossref","first-page":"D141","DOI":"10.1093\/nar\/gkn879","article-title":"The Ribosomal Database Project: improved alignments and new tools for rRNA analysis","volume":"37","author":"Cole","year":"2009","journal-title":"Nucleic Acids Res."},{"key":"2023012508001908600_B15","doi-asserted-by":"crossref","first-page":"629","DOI":"10.1038\/nature06810","article-title":"Functional metagenomic profiling of nine biomes","volume":"452","author":"Dinsdale","year":"2008","journal-title":"Nature"},{"key":"2023012508001908600_B16","doi-asserted-by":"crossref","first-page":"e1584","DOI":"10.1371\/journal.pone.0001584","article-title":"Microbial ecology of four coral atolls in the Northern Line Islands","volume":"3","author":"Dinsdale","year":"2008","journal-title":"PLoS ONE"},{"key":"2023012508001908600_B17","doi-asserted-by":"crossref","first-page":"57","DOI":"10.1186\/1471-2164-7-57","article-title":"Using pyrosequencing to shed light on deep mine microbial ecology","volume":"7","author":"Edwards","year":"2006","journal-title":"BMC Genomics"},{"key":"2023012508001908600_B18","doi-asserted-by":"crossref","first-page":"163","DOI":"10.1101\/gr.8.3.163","article-title":"Phylogenomics: improving functional predictions for uncharacterized genes by evolutionary analysis","volume":"8","author":"Eisen","year":"1998","journal-title":"Genome Res."},{"key":"2023012508001908600_B19","doi-asserted-by":"crossref","first-page":"225","DOI":"10.1093\/bib\/bbl004","article-title":"Automated protein function prediction\u2013the genomic challenge","volume":"7","author":"Friedberg","year":"2006","journal-title":"Brief. Bioinform."},{"key":"2023012508001908600_B20","doi-asserted-by":"crossref","first-page":"1263","DOI":"10.1038\/nbt1247","article-title":"Metagenomic analysis of two enhanced biological phosphorus removal (EBPR) sludge communities","volume":"24","author":"Garc\u00eda","year":"2006","journal-title":"Nat. Biotechnol."},{"key":"2023012508001908600_B21","doi-asserted-by":"crossref","first-page":"1374","DOI":"10.1073\/pnas.0808022106","article-title":"Quantifying environmental adaptation of metabolic pathways in metagenomics","volume":"106","author":"Gianoulis","year":"2009","journal-title":"Proc. Natl Acad. Sci. USA"},{"key":"2023012508001908600_B22","doi-asserted-by":"crossref","first-page":"999","DOI":"10.1080\/03610918708812633","article-title":"A comparison of some conditional and unconditional exact tests for 2 \u00d7 2 contingency tables","volume":"16","author":"Haber","year":"1987","journal-title":"Commun. Stat. Simul."},{"key":"2023012508001908600_B23","doi-asserted-by":"crossref","first-page":"1457","DOI":"10.1126\/science.1100025","article-title":"Reverse methanogenesis: testing the hypothesis with environmental genomics","volume":"305","author":"Hallam","year":"2004","journal-title":"Science"},{"key":"2023012508001908600_B24","doi-asserted-by":"crossref","first-page":"1141","DOI":"10.1101\/gr.085464.108","article-title":"Microbial community profiling for human microbiome projects: tools, techniques, and challenges","volume":"19","author":"Hamady","year":"2009","journal-title":"Genome Res."},{"key":"2023012508001908600_B25","doi-asserted-by":"crossref","first-page":"D277","DOI":"10.1093\/nar\/gkh063","article-title":"The KEGG resource for deciphering the genome","volume":"32","author":"Kanehisa","year":"2004","journal-title":"Nucleic Acids Res."},{"key":"2023012508001908600_B26","doi-asserted-by":"crossref","first-page":"2737","DOI":"10.1093\/bioinformatics\/btp508","article-title":"ShotgunFunctionalizeR: an R-package for functional comparison of metagenomes","volume":"25","author":"Kristiansson","year":"2009","journal-title":"Bioinformatics"},{"key":"2023012508001908600_B27","doi-asserted-by":"crossref","first-page":"1713","DOI":"10.1093\/bioinformatics\/btm239","article-title":"Bioinformatics software for biologists in the genomics era","volume":"23","author":"Kumar","year":"2007","journal-title":"Bioinformatics"},{"key":"2023012508001908600_B28","doi-asserted-by":"crossref","first-page":"293","DOI":"10.1101\/gr.6835308","article-title":"A bacterial metapopulation adapts locally to phage predation despite global dispersal","volume":"18","author":"Kunin","year":"2008","journal-title":"Genome Res."},{"key":"2023012508001908600_B29","doi-asserted-by":"crossref","first-page":"1095","DOI":"10.1081\/SAC-200040691","article-title":"Small sample confidence intervals for odds ratio","volume":"33","author":"Lawson","year":"2004","journal-title":"Commun. Stat. Simul."},{"key":"2023012508001908600_B30","doi-asserted-by":"crossref","first-page":"1022","DOI":"10.1038\/4441022a","article-title":"Microbial ecology: human gut microbes associated with obesity","volume":"444","author":"Ley","year":"2006","journal-title":"Nature"},{"key":"2023012508001908600_B31","doi-asserted-by":"crossref","first-page":"8228","DOI":"10.1128\/AEM.71.12.8228-8235.2005","article-title":"UniFrac: a new phylogenetic method for comparing microbial communities","volume":"71","author":"Lozupone","year":"2005","journal-title":"Appl. Environ. Microbiol."},{"key":"2023012508001908600_B32","doi-asserted-by":"crossref","first-page":"1430","DOI":"10.1093\/ije\/dyn162","article-title":"Analysis of 2 x 2 tables of frequencies: matching test to experimental design","volume":"37","author":"Ludbrook","year":"2008","journal-title":"Int. J. Epidemiol."},{"key":"2023012508001908600_B33","first-page":"455","volume-title":"Manly: Randomization, bootstrap and Monte Carlo methods in biology","author":"Manly","year":"2007","edition":"3rd"},{"key":"2023012508001908600_B34","doi-asserted-by":"crossref","first-page":"D534","DOI":"10.1093\/nar\/gkm869","article-title":"IMG\/M: a data management and analysis system for metagenomes","volume":"36","author":"Markowitz","year":"2008","journal-title":"Nucleic Acids Res."},{"key":"2023012508001908600_B35","doi-asserted-by":"crossref","first-page":"137","DOI":"10.1023\/A:1018573716156","article-title":"Simplifying the calculation of the P-value for Barnard's test and its derivatives","volume":"7","author":"Mato","year":"1997","journal-title":"Stat. Comput."},{"key":"2023012508001908600_B36","author":"Mehta","year":"2003","journal-title":"Conditional versus unconditional exact tests for comparing two binomials."},{"key":"2023012508001908600_B37","doi-asserted-by":"crossref","first-page":"386","DOI":"10.1186\/1471-2105-9-386","article-title":"The metagenomics RAST server \u2013 a public resource for the automatic phylogenetic and functional analysis of metagenomes","volume":"9","author":"Meyer","year":"2008","journal-title":"BMC Bioinformatics"},{"key":"2023012508001908600_B38","doi-asserted-by":"crossref","first-page":"1849","DOI":"10.1093\/bioinformatics\/btp341","article-title":"Visual and statistical comparison of metagenomes","volume":"25","author":"Mitra","year":"2009","journal-title":"Bioinformatics"},{"key":"2023012508001908600_B39","doi-asserted-by":"crossref","first-page":"708","DOI":"10.1038\/nature06513","article-title":"Bacterial carbon processing by generalist species in the coastal ocean","volume":"451","author":"Mou","year":"2008","journal-title":"Nature"},{"key":"2023012508001908600_B40","doi-asserted-by":"crossref","first-page":"591","DOI":"10.1111\/j.1469-185X.2007.00027.x","article-title":"Effect size, confidence interval and statistical significance: a practical guide for biologists","volume":"82","author":"Nakagawa","year":"2007","journal-title":"Biol. Rev. Camb. Phil. Soc."},{"key":"2023012508001908600_B41","doi-asserted-by":"crossref","first-page":"873","DOI":"10.1002\/(SICI)1097-0258(19980430)17:8<873::AID-SIM779>3.0.CO;2-I","article-title":"Interval estimation for the difference between independent proportions: comparison of eleven methods","volume":"17","author":"Newcombe","year":"1998","journal-title":"Stat. Med."},{"key":"2023012508001908600_B42","doi-asserted-by":"crossref","first-page":"5891","DOI":"10.1093\/nar\/gki866","article-title":"The subsystems approach to genome annotation and its use in the project to annotate 1000 genomes","volume":"33","author":"Overbeek","year":"2005","journal-title":"Nucleic Acids Res."},{"key":"2023012508001908600_B43","doi-asserted-by":"crossref","first-page":"1358","DOI":"10.1111\/j.1462-2920.2008.01863.x","article-title":"Comparative day\/night metatranscriptomic analysis of microbial communities in the North Pacific subtropical gyre","volume":"11","author":"Poretsky","year":"2009","journal-title":"Env. Microbiol."},{"key":"2023012508001908600_B44","doi-asserted-by":"crossref","first-page":"e2945","DOI":"10.1371\/journal.pone.0002945","article-title":"Comparative metagenomics reveals host specific metavirulomes and horizontal gene transfer elements in the chicken cecum microbiome","volume":"3","author":"Qu","year":"2008","journal-title":"PLoS ONE"},{"key":"2023012508001908600_B45","doi-asserted-by":"crossref","first-page":"401","DOI":"10.1093\/bioinformatics\/btl633","article-title":"Enrichment or depletion of a GO category within a class of genes: which test?","volume":"23","author":"Rivals","year":"2007","journal-title":"Bioinformatics"},{"key":"2023012508001908600_B46","doi-asserted-by":"crossref","first-page":"162","DOI":"10.1186\/1471-2105-7-162","article-title":"An application of statistics to comparative metagenomics","volume":"7","author":"Rodriguez-Brito","year":"2006","journal-title":"BMC Bioinformatics"},{"key":"2023012508001908600_B47","volume-title":"Contrasts and Effect Sizes in Behavioral Research: A Correlational Approach.","author":"Rosenthal","year":"2000"},{"key":"2023012508001908600_B48","first-page":"164","article-title":"Down with odds ratios!","volume":"1","author":"Sackett","year":"1996","journal-title":"Evidence-based Med."},{"key":"2023012508001908600_B49","doi-asserted-by":"crossref","first-page":"7537","DOI":"10.1128\/AEM.01541-09","article-title":"Introducing mothur: open-source, platform-independent, community-supported software for describing and comparing microbial communities","volume":"75","author":"Schloss","year":"2009","journal-title":"Appl. Environ. Microbiol."},{"key":"2023012508001908600_B50","doi-asserted-by":"crossref","first-page":"e1000605","DOI":"10.1371\/journal.pcbi.1000605","article-title":"Annotation error in public databases: misannotation of molecular function in enzyme superfamiles","volume":"5","author":"Schnoes","year":"2009","journal-title":"PLoS Comput. Biol."},{"key":"2023012508001908600_B51","doi-asserted-by":"crossref","first-page":"12","DOI":"10.1148\/radiol.2301031028","article-title":"Proportions, odds, and risk","volume":"230","author":"Sistrom","year":"2004","journal-title":"Radiology"},{"key":"2023012508001908600_B52","doi-asserted-by":"crossref","first-page":"9440","DOI":"10.1073\/pnas.1530509100","article-title":"Statistical significance for genomewide studies","volume":"100","author":"Storey","year":"2003","journal-title":"Proc. Natl Acad. Sci. USA"},{"key":"2023012508001908600_B53","doi-asserted-by":"crossref","first-page":"187","DOI":"10.1111\/j.1467-9868.2004.00439.x","article-title":"Strong control, conservative point estimation, and simultaneous conservative consistency of false discovery rates: a unified approach","volume":"66","author":"Storey","year":"2004","journal-title":"J. Royal Stat. Soc. B"},{"key":"2023012508001908600_B54","doi-asserted-by":"crossref","first-page":"554","DOI":"10.1126\/science.1107851","article-title":"Comparative metagenomics of microbial communities","volume":"308","author":"Tringe","year":"2005","journal-title":"Science"},{"key":"2023012508001908600_B55","doi-asserted-by":"crossref","first-page":"1027","DOI":"10.1038\/nature05414","article-title":"An obesity-associated gut microbiome with increased capacity for energy harvest","volume":"444","author":"Turnbaugh","year":"2006","journal-title":"Nature"},{"key":"2023012508001908600_B56","doi-asserted-by":"crossref","first-page":"480","DOI":"10.1038\/nature07540","article-title":"A core gut microbiome in obese and lean twins","volume":"457","author":"Turnbaugh","year":"2009","journal-title":"Nature"},{"key":"2023012508001908600_B57","doi-asserted-by":"crossref","first-page":"e2527","DOI":"10.1371\/journal.pone.0002527","article-title":"Simultaneous assessment of soil microbial community structure and function through analysis of the meta-transcriptome","volume":"3","author":"Urich","year":"2008","journal-title":"PLoS ONE"},{"key":"2023012508001908600_B58","doi-asserted-by":"crossref","first-page":"e1000352","DOI":"10.1371\/journal.pcbi.1000352","article-title":"Statistical methods for detecting differentially abundant features in clinical metagenomic samples","volume":"5","author":"White","year":"2009","journal-title":"PLoS Comput. Biol."},{"key":"2023012508001908600_B59","doi-asserted-by":"crossref","first-page":"e7370","DOI":"10.1371\/journal.pone.0007370","article-title":"Metagenomic analysis of respiratory tract DNA viral communities in cystic fibrosis and non-cystic fibrosis individuals","volume":"4","author":"Willner","year":"2009","journal-title":"PLoS ONE"},{"key":"2023012508001908600_B60","doi-asserted-by":"crossref","first-page":"e16","DOI":"10.1371\/journal.pbio.0050016","article-title":"The Sorcerer II Global Ocean Sampling expedition: expanding the universe of protein families","volume":"5","author":"Yooseph","year":"2007","journal-title":"PLoS Biol."}],"container-title":["Bioinformatics"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/academic.oup.com\/bioinformatics\/article-pdf\/26\/6\/715\/48853190\/bioinformatics_26_6_715.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"syndication"},{"URL":"https:\/\/academic.oup.com\/bioinformatics\/article-pdf\/26\/6\/715\/48853190\/bioinformatics_26_6_715.pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,2,17]],"date-time":"2025-02-17T04:47:02Z","timestamp":1739767622000},"score":1,"resource":{"primary":{"URL":"https:\/\/academic.oup.com\/bioinformatics\/article\/26\/6\/715\/245265"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2010,2,3]]},"references-count":60,"journal-issue":{"issue":"6","published-print":{"date-parts":[[2010,3,15]]}},"URL":"https:\/\/doi.org\/10.1093\/bioinformatics\/btq041","relation":{"has-review":[{"id-type":"doi","id":"10.3410\/f.13354958.14725136","asserted-by":"object"}]},"ISSN":["1367-4811","1367-4803"],"issn-type":[{"value":"1367-4811","type":"electronic"},{"value":"1367-4803","type":"print"}],"subject":[],"published-other":{"date-parts":[[2010,3,15]]},"published":{"date-parts":[[2010,2,3]]}}}