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Cited by 333

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Piphillin: Improved Prediction of Metagenomic Content by Direct Inference from Human Microbiomes

Open access
Iwai, Shoko, Weinmaier, Thomas, Schmidt, Brian L., Albertson, Donna G., Poloso, Neil J., Dabbagh, Karim, DeSantis, Todd Z.·2016·PLOS ONE

Abstract

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 However, those tools have important limitations since they rely on outdated functional databases and uncertain phylogenetic trees and require very specific data pre-processing protocols.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.

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Metadata

Authors
Iwai, S., Weinmaier, T., Schmidt, B. L., Albertson, D. G., Poloso, N. J., Dabbagh, K., & DeSantis, T. Z.
Venue
PLOS ONE
Published
2016-11-07
Volume
11
Issue
11
Pages
e0166104
ISSN
1932-6203 (ISSN-L)
OpenAlex
W2555180552
Cited by
333
References
8
FWCI
12.34
Type
journal article
Language
en
Open access
gold

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CoChat. (2026). Citation check: Piphillin: Improved Prediction of Metagenomic Content by Direct Inference from Human Microbiomes. https://app.cochat.ai/papers/10.1371/journal.pone.0166104
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Iwai, S., Weinmaier, T., Schmidt, B. L., Albertson, D. G., Poloso, N. J., Dabbagh, K., & DeSantis, T. Z. (2016). Piphillin: Improved Prediction of Metagenomic Content by Direct Inference from Human Microbiomes. PLOS ONE. https://doi.org/10.1371/journal.pone.0166104

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