Differential Abundance Analysis for Microbial Marker-gene Surveys

Overview

Journal Nat Methods

Specialties Biomedical Engineering
Pathology

Date 2013 Oct 1

PMID 24076764

Citations 1069

Authors

Joseph N Paulson

O Colin Stine

Hector Corrada Bravo

Mihai Pop

Affiliations

Soon will be listed here.

Abstract

We introduce a methodology to assess differential abundance in sparse high-throughput microbial marker-gene survey data. Our approach, implemented in the metagenomeSeq Bioconductor package, relies on a novel normalization technique and a statistical model that accounts for undersampling-a common feature of large-scale marker-gene studies. Using simulated data and several published microbiota data sets, we show that metagenomeSeq outperforms the tools currently used in this field.

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References

Ghodsi M, Liu B, Pop M . DNACLUST: accurate and efficient clustering of phylogenetic marker genes. BMC Bioinformatics. 2011; 12:271. PMC: 3213679. DOI: 10.1186/1471-2105-12-271. View

Bullard J, Purdom E, Hansen K, Dudoit S . Evaluation of statistical methods for normalization and differential expression in mRNA-Seq experiments. BMC Bioinformatics. 2010; 11:94. PMC: 2838869. DOI: 10.1186/1471-2105-11-94. View

Friedman J, Alm E . Inferring correlation networks from genomic survey data. PLoS Comput Biol. 2012; 8(9):e1002687. PMC: 3447976. DOI: 10.1371/journal.pcbi.1002687. View

. A framework for human microbiome research. Nature. 2012; 486(7402):215-21. PMC: 3377744. DOI: 10.1038/nature11209. View

Faust K, Sathirapongsasuti J, Izard J, Segata N, Gevers D, Raes J . Microbial co-occurrence relationships in the human microbiome. PLoS Comput Biol. 2012; 8(7):e1002606. PMC: 3395616. DOI: 10.1371/journal.pcbi.1002606. View

Wang Q, Garrity G, Tiedje J, Cole J . Naive Bayesian classifier for rapid assignment of rRNA sequences into the new bacterial taxonomy. Appl Environ Microbiol. 2007; 73(16):5261-7. PMC: 1950982. DOI: 10.1128/AEM.00062-07. View

Anders S, Huber W . Differential expression analysis for sequence count data. Genome Biol. 2010; 11(10):R106. PMC: 3218662. DOI: 10.1186/gb-2010-11-10-r106. View

Charlson E, Bittinger K, Haas A, Fitzgerald A, Frank I, Yadav A . Topographical continuity of bacterial populations in the healthy human respiratory tract. Am J Respir Crit Care Med. 2011; 184(8):957-63. PMC: 3208663. DOI: 10.1164/rccm.201104-0655OC. View

Turnbaugh P, Ridaura V, Faith J, Rey F, Knight R, Gordon J . The effect of diet on the human gut microbiome: a metagenomic analysis in humanized gnotobiotic mice. Sci Transl Med. 2010; 1(6):6ra14. PMC: 2894525. DOI: 10.1126/scitranslmed.3000322. View

10.

Dillies M, Rau A, Aubert J, Hennequet-Antier C, Jeanmougin M, Servant N . A comprehensive evaluation of normalization methods for Illumina high-throughput RNA sequencing data analysis. Brief Bioinform. 2012; 14(6):671-83. DOI: 10.1093/bib/bbs046. View

11.

White J, Navlakha S, Nagarajan N, Ghodsi M, Kingsford C, Pop M . Alignment and clustering of phylogenetic markers--implications for microbial diversity studies. BMC Bioinformatics. 2010; 11:152. PMC: 2859756. DOI: 10.1186/1471-2105-11-152. View

12.

Paster B, Boches S, Galvin J, Ericson R, Lau C, Levanos V . Bacterial diversity in human subgingival plaque. J Bacteriol. 2001; 183(12):3770-83. PMC: 95255. DOI: 10.1128/JB.183.12.3770-3783.2001. View

13.

Scher J, Ubeda C, Equinda M, Khanin R, Buischi Y, Viale A . Periodontal disease and the oral microbiota in new-onset rheumatoid arthritis. Arthritis Rheum. 2012; 64(10):3083-94. PMC: 3428472. DOI: 10.1002/art.34539. View

14.

White J, Nagarajan N, Pop M . Statistical methods for detecting differentially abundant features in clinical metagenomic samples. PLoS Comput Biol. 2009; 5(4):e1000352. PMC: 2661018. DOI: 10.1371/journal.pcbi.1000352. View

15.

Segata N, Haake S, Mannon P, Lemon K, Waldron L, Gevers D . Composition of the adult digestive tract bacterial microbiome based on seven mouth surfaces, tonsils, throat and stool samples. Genome Biol. 2012; 13(6):R42. PMC: 3446314. DOI: 10.1186/gb-2012-13-6-r42. View

16.

Frazee A, Langmead B, Leek J . ReCount: a multi-experiment resource of analysis-ready RNA-seq gene count datasets. BMC Bioinformatics. 2011; 12:449. PMC: 3229291. DOI: 10.1186/1471-2105-12-449. View

17.

Turnbaugh P, Hamady M, Yatsunenko T, Cantarel B, Duncan A, Ley R . A core gut microbiome in obese and lean twins. Nature. 2008; 457(7228):480-4. PMC: 2677729. DOI: 10.1038/nature07540. View

18.

Ravel J, Gajer P, Abdo Z, Schneider G, Koenig S, McCulle S . Vaginal microbiome of reproductive-age women. Proc Natl Acad Sci U S A. 2010; 108 Suppl 1:4680-7. PMC: 3063603. DOI: 10.1073/pnas.1002611107. View

19.

Robinson M, McCarthy D, Smyth G . edgeR: a Bioconductor package for differential expression analysis of digital gene expression data. Bioinformatics. 2009; 26(1):139-40. PMC: 2796818. DOI: 10.1093/bioinformatics/btp616. View

20.

Harris J, Wagner B . Bacterial identification and analytic challenges in clinical microbiome studies. J Allergy Clin Immunol. 2012; 129(2):441-2. DOI: 10.1016/j.jaci.2011.12.969. View