Phylogenize2: robust phylogenetic methods link genes to phenotypes across host-associated and environmental...

Area of Science:

• Microbiology
• Bioinformatics
• Genomics

Background:

• Phylogenetic relationships often confound associations between microbial functions and environmental factors in microbiome research.
• Existing methods to address this confounder require genome content data, limiting their application in under-resourced biomes.
• There is a need for accessible tools that can link microbial functions to abundance while accounting for phylogeny across diverse environments.

Purpose of the Study:

• To develop and present Phylogenize2, a redesigned phylogeny-aware tool for linking microbial gene families to abundance phenotypes.
• To expand the applicability of phylogeny-aware microbiome analysis to environments beyond the human gut.
• To provide insights into the genetic basis of microbiome-encoded traits in diverse ecosystems.

Main Methods:

• Phylogenize2 integrates large metagenome-assembled genome collections (MGnify, GlobDB) to increase species coverage.
• It employs a robust phylogenetic testing framework optimized for microbial abundance data.
• The tool allows for the use of alternative comparative methods, such as POMS.

Main Results:

• Phylogenize2 successfully applied to mouse gut and polar ocean environments, demonstrating expanded utility.
• In mice on a high-fat diet, Phylogenize2 identified thioredoxin family proteins in Muribaculaceae, linked to oxidative stress.
• In a polar ocean study, a specific aldehyde oxidoreductase system was found to differentiate microbial communities, suggesting a role in aldehyde detoxification.

Conclusions:

• Phylogenize2 enhances the accessibility and scope of phylogeny-aware microbiome analysis.
• The tool provides valuable insights into the functional roles of microbes in diverse environments, such as diet-induced changes in the mouse gut and adaptation in marine ecosystems.
• Phylogenize2 facilitates the discovery of the genetic underpinnings of microbiome functions across various biomes.