{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,2,27]],"date-time":"2026-02-27T06:22:35Z","timestamp":1772173355314,"version":"3.50.1"},"reference-count":45,"publisher":"Public Library of Science (PLoS)","issue":"4","license":[{"start":{"date-parts":[[2025,4,4]],"date-time":"2025-04-04T00:00:00Z","timestamp":1743724800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100000001","name":"National Science Foundation","doi-asserted-by":"publisher","award":["2006069 and 2316233"],"award-info":[{"award-number":["2006069 and 2316233"]}],"id":[{"id":"10.13039\/100000001","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["www.ploscompbiol.org"],"crossmark-restriction":false},"short-container-title":["PLoS Comput Biol"],"abstract":"<jats:p>\n                    We present TIPP3 and TIPP3-fast, new tools for abundance profiling in metagenomic datasets. Like its predecessor, TIPP2, the TIPP3 pipeline uses a maximum likelihood approach to place reads into labeled taxonomies using marker genes, but it achieves superior accuracy to TIPP2 by enabling the use of much larger taxonomies through improved algorithmic techniques. We show that TIPP3 is generally more accurate than leading methods for abundance profiling in two important contexts: when reads come from genomes not already in a public database (i.e., novel genomes) and when reads contain sequencing errors. We also show that TIPP3-fast has slightly lower accuracy than TIPP3, but is also generally more accurate than other leading methods and uses a small fraction of TIPP3\u2019s runtime. Additionally, we highlight the potential benefits of restricting abundance profiling methods to those reads that map to marker genes (i.e., using a filtered marker-gene based analysis), which we show typically improves accuracy. TIPP3 is freely available at\n                    <jats:ext-link xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" ext-link-type=\"uri\" xlink:href=\"https:\/\/github.com\/c5shen\/TIPP3\" xlink:type=\"simple\">https:\/\/github.com\/c5shen\/TIPP3<\/jats:ext-link>\n                    .\n                  <\/jats:p>","DOI":"10.1371\/journal.pcbi.1012593","type":"journal-article","created":{"date-parts":[[2025,4,4]],"date-time":"2025-04-04T13:55:31Z","timestamp":1743774931000},"page":"e1012593","update-policy":"https:\/\/doi.org\/10.1371\/journal.pcbi.corrections_policy","source":"Crossref","is-referenced-by-count":2,"title":["TIPP3 and TIPP3-fast: Improved abundance profiling in metagenomics"],"prefix":"10.1371","volume":"21","author":[{"given":"Chengze","family":"Shen","sequence":"first","affiliation":[]},{"given":"Eleanor","family":"Wedell","sequence":"additional","affiliation":[]},{"given":"Mihai","family":"Pop","sequence":"additional","affiliation":[]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7717-3514","authenticated-orcid":true,"given":"Tandy","family":"Warnow","sequence":"additional","affiliation":[]}],"member":"340","published-online":{"date-parts":[[2025,4,4]]},"reference":[{"issue":"1","key":"pcbi.1012593.ref001","doi-asserted-by":"crossref","DOI":"10.1186\/s12915-014-0069-1","article-title":"The Earth Microbiome project: successes and aspirations","volume":"12","author":"JA Gilbert","year":"2014","journal-title":"BMC Biol"},{"issue":"7750","key":"pcbi.1012593.ref002","doi-asserted-by":"crossref","first-page":"43","DOI":"10.1038\/s41586-019-1065-y","article-title":"Structural variation in the gut microbiome associates with host health","volume":"568","author":"D Zeevi","year":"2019","journal-title":"Nature"},{"issue":"1","key":"pcbi.1012593.ref003","doi-asserted-by":"crossref","first-page":"55","DOI":"10.1038\/s41579-020-0433-9","article-title":"Gut microbiota in human metabolic health and disease","volume":"19","author":"Y Fan","year":"2021","journal-title":"Nat Rev Microbiol"},{"issue":"2","key":"pcbi.1012593.ref004","doi-asserted-by":"crossref","first-page":"295","DOI":"10.1038\/s41591-022-01686-6","article-title":"Metabolomic and microbiome profiling reveals personalized risk factors for coronary artery disease","volume":"28","author":"Y Talmor-Barkan","year":"2022","journal-title":"Nat Med"},{"issue":"1","key":"pcbi.1012593.ref005","doi-asserted-by":"crossref","first-page":"181","DOI":"10.1093\/nar\/29.1.181","article-title":"rrndb: the Ribosomal RNA operon copy number database","volume":"29","author":"JA Klappenbach","year":"2001","journal-title":"Nucleic Acids Res"},{"issue":"2","key":"pcbi.1012593.ref006","doi-asserted-by":"crossref","first-page":"535","DOI":"10.1007\/s00248-020-01586-7","article-title":"16S rRNA gene copy number normalization does not provide more reliable conclusions in metataxonomic surveys","volume":"81","author":"R Starke","year":"2021","journal-title":"Microb Ecol"},{"issue":"3","key":"pcbi.1012593.ref007","doi-asserted-by":"crossref","first-page":"R46","DOI":"10.1186\/gb-2014-15-3-r46","article-title":"Kraken: ultrafast metagenomic sequence classification using exact alignments","volume":"15","author":"DE Wood","year":"2014","journal-title":"Genome Biol"},{"issue":"1","key":"pcbi.1012593.ref008","doi-asserted-by":"crossref","first-page":"257","DOI":"10.1186\/s13059-019-1891-0","article-title":"Improved metagenomic analysis with Kraken 2","volume":"20","author":"DE Wood","year":"2019","journal-title":"Genome Biol"},{"key":"pcbi.1012593.ref009","doi-asserted-by":"crossref","first-page":"e104","DOI":"10.7717\/peerj-cs.104","article-title":"Bracken: estimating species abundance in metagenomics data","volume":"3","author":"J Lu","year":"2017","journal-title":"PeerJ Computer Science"},{"issue":"6","key":"pcbi.1012593.ref010","doi-asserted-by":"crossref","first-page":"971","DOI":"10.1038\/s41592-024-02273-y","article-title":"Metabuli: sensitive and specific metagenomic classification via joint analysis of amino acid and DNA","volume":"21","author":"J Kim","year":"2024","journal-title":"Nat Methods"},{"key":"pcbi.1012593.ref011","doi-asserted-by":"crossref","unstructured":"Liu B, Gibbons T, Ghodsi M, Pop M. 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