Piphillin: Improved Prediction of Metagenomic Content by Direct Inference from Human Microbiomes.
Functional analysis of a clinical microbiome facilitates the elucidation of mechanisms by which microbiome perturbation can cause a phenotypic change in the patient. The direct approach for the analysis of the functional capacity of the microbiome is via shotgun metagenomics. An inexpensive method to estimate the functional capacity of a microbial community is through collecting 16S rRNA gene profiles then indirectly inferring the abundance of functional genes. This inference approach has been implemented in the PICRUSt and Tax4Fun software tools. However, those tools have important limitations since they rely on outdated functional databases and uncertain phylogenetic trees and require very specific data pre-processing protocols. Here we introduce Piphillin, a straightforward algorithm independent of any proposed phylogenetic tree, leveraging contemporary functional databases and not obliged to any singular data pre-processing protocol. When all three inference tools were evaluated against actual shotgun metagenomics, Piphillin was superior in predicting gene composition in human clinical samples compared to both PICRUSt and Tax4Fun (p<0.01 and p<0.001, respectively) and Piphillin's ability to predict disease associations with specific gene orthologs exhibited a 15% increase in balanced accuracy compared to PICRUSt. From laboratory animal samples, no performance advantage was observed for any one of the tools over the others and for environmental samples all produced unsatisfactory predictions. Our results demonstrate that functional inference using the direct method implemented in Piphillin is preferable for clinical biospecimens. Piphillin is publicly available for academic use at http://secondgenome.com/Piphillin.
Informatics Department, Second Genome Inc., South San Francisco, California, United States of America.
Shoko
S
Iwai
Informatics Department, Second Genome Inc., South San Francisco, California, United States of America.
Thomas
T
Weinmaier
Bluestone Center for Clinical Research and the Department of Oral and Maxillofacial Surgery, New York University College of Dentistry, New York, New York, United States of America.
Brian L
BL
Schmidt
Bluestone Center for Clinical Research and the Department of Oral and Maxillofacial Surgery, New York University College of Dentistry, New York, New York, United States of America.|Helen Diller Family Comprehensive Cancer Center, University of California San Francisco, San Francisco, California, United States of America.
Donna G
DG
Albertson
Research and External Scientific Innovation Department, Allergan PLC, Irvine, California, United States of America.
Neil J
NJ
Poloso
Informatics Department, Second Genome Inc., South San Francisco, California, United States of America.
Karim
K
Dabbagh
Informatics Department, Second Genome Inc., South San Francisco, California, United States of America.
Todd Z
TZ
DeSantis
D000465:Algorithms; D016208:Databases, Factual; D006801:Humans; D054892:Metagenome / Q000235:genetics*; D056186:Metagenomics / Q000379:methods*; D064307:Microbiota / Q000235:genetics*; D010802:Phylogeny; D012336:RNA, Ribosomal, 16S; D012984:Software
D012336:RNA, Ribosomal, 16S