Clustering co-abundant genes identifies components of the gut microbiome that are reproducibly associated with colorectal cancer and inflammatory bowel disease.

Microbiome
Samuel S. Minot, Amy D. Willis

Abstract

Whole-genome "shotgun" (WGS) metagenomic sequencing is an increasingly widely used tool for analyzing the metagenomic content of microbiome samples. While WGS data contains gene-level information, it can be challenging to analyze the millions of microbial genes which are typically found in microbiome experiments. To mitigate the ultrahigh dimensionality challenge of gene-level metagenomics, it has been proposed to cluster genes by co-abundance to form Co-Abundant Gene groups (CAGs). However, exhaustive co-abundance clustering of millions of microbial genes across thousands of biological samples has previously been intractable purely due to the computational challenge of performing trillions of pairwise comparisons. Here we present a novel computational approach to the analysis of WGS datasets in which microbial gene groups are the fundamental unit of analysis. We use the Approximate Nearest Neighbor heuristic for near-exhaustive average linkage clustering to group millions of genes by co-abundance. This results in thousands of high-quality CAGs representing complete and partial microbial genomes. We applied this method to publicly available WGS microbiome surveys and found that the resulting microbial CAGs associated with infla...Continue Reading

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Citations

May 11, 2021·Journal of Applied Statistics·Alex Paynter, Amy D Willis
Apr 22, 2021·The Journal of Infectious Diseases·Jonathan L Golob, Krishna Rao
May 26, 2021·Annual Review of Virology·Pacifica SommersGareth Trubl

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Methods Mentioned

BETA
single-cell sequencing

Software Mentioned

DIAMOND
ann
Docker
HUMAnN2
AWS
Batch
GCP
Azure
eggNOG
PBS

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