Robust methods for differential abundance analysis in marker gene surveys

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.

[1]  P. Langendijk-Genevaux,et al.  Sulfate-reducing bacteria in relation with other potential periodontal pathogens. , 2001, Journal of clinical periodontology.

[2]  F. Dewhirst,et al.  Bacterial Diversity in Human Subgingival Plaque , 2001, Journal of bacteriology.

[3]  R. Knight,et al.  UniFrac: a New Phylogenetic Method for Comparing Microbial Communities , 2005, Applied and Environmental Microbiology.

[4]  Rafael A. Irizarry,et al.  Bioinformatics and Computational Biology Solutions using R and Bioconductor , 2005 .

[5]  Forest Rohwer,et al.  An application of statistics to comparative metagenomics , 2006, BMC Bioinformatics.

[6]  J. Davis Bioinformatics and Computational Biology Solutions Using R and Bioconductor , 2007 .

[7]  J. Tiedje,et al.  Naïve Bayesian Classifier for Rapid Assignment of rRNA Sequences into the New Bacterial Taxonomy , 2007, Applied and Environmental Microbiology.

[8]  S. Socransky,et al.  Comparisons of subgingival microbial profiles of refractory periodontitis, severe periodontitis, and periodontal health using the human oral microbe identification microarray. , 2009, Journal of periodontology.

[9]  Sandrine Dudoit,et al.  Evaluation of statistical methods for normalization and differential expression in mRNA-Seq experiments , 2010, BMC Bioinformatics.

[10]  Mihai Pop,et al.  Statistical Methods for Detecting Differentially Abundant Features in Clinical Metagenomic Samples , 2009, PLoS Comput. Biol..

[11]  R. Knight,et al.  The Effect of Diet on the Human Gut Microbiome: A Metagenomic Analysis in Humanized Gnotobiotic Mice , 2009, Science Translational Medicine.

[12]  Mihai Pop,et al.  Alignment and clustering of phylogenetic markers - implications for microbial diversity studies , 2010, BMC Bioinformatics.

[13]  B. Roe,et al.  A core gut microbiome in obese and lean twins , 2008, Nature.

[14]  P. Gajer,et al.  Vaginal microbiome of reproductive-age women , 2010, Proceedings of the National Academy of Sciences.

[15]  B. Langmead,et al.  Cloud-scale RNA-sequencing differential expression analysis with Myrna , 2010, Genome Biology.

[16]  William A. Walters,et al.  QIIME allows analysis of high-throughput community sequencing data , 2010, Nature Methods.

[17]  W. Huber,et al.  which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. MAnorm: a robust model for quantitative comparison of ChIP-Seq data sets , 2011 .

[18]  Mark D. Robinson,et al.  edgeR: a Bioconductor package for differential expression analysis of digital gene expression data , 2009, Bioinform..

[19]  Kyle Bittinger,et al.  Topographical continuity of bacterial populations in the healthy human respiratory tract. , 2011, American journal of respiratory and critical care medicine.

[20]  C. Huttenhower,et al.  Metagenomic biomarker discovery and explanation , 2011, Genome Biology.

[21]  Mihai Pop,et al.  DNACLUST: accurate and efficient clustering of phylogenetic marker genes , 2011, BMC Bioinformatics.

[22]  Alyssa C. Frazee,et al.  ReCount: A multi-experiment resource of analysis-ready RNA-seq gene count datasets , 2011, BMC Bioinformatics.

[23]  Timothy L. Tickle,et al.  Dysfunction of the intestinal microbiome in inflammatory bowel disease and treatment , 2012, Genome Biology.

[24]  Levi Waldron,et al.  Composition of the adult digestive tract bacterial microbiome based on seven mouth surfaces, tonsils, throat and stool samples , 2012, Genome Biology.

[25]  Jonathan Friedman,et al.  Inferring Correlation Networks from Genomic Survey Data , 2012, PLoS Comput. Biol..

[26]  Katherine H. Huang,et al.  A framework for human microbiome research , 2012, Nature.

[27]  J. Harris,et al.  Bacterial identification and analytic challenges in clinical microbiome studies. , 2012, The Journal of allergy and clinical immunology.

[28]  Qiang Feng,et al.  A metagenome-wide association study of gut microbiota in type 2 diabetes , 2012, Nature.

[29]  Curtis Huttenhower,et al.  Microbial Co-occurrence Relationships in the Human Microbiome , 2012, PLoS Comput. Biol..

[30]  A. Viale,et al.  Periodontal disease and the oral microbiota in new-onset rheumatoid arthritis. , 2012, Arthritis and rheumatism.