Multi-omic integration of microbiome data for identifying disease-associated modules

Abstract Multi-omic studies of the human gut microbiome are crucial for understanding its role in disease across multiple functional layers. Nevertheless, integrating and analyzing such complex datasets poses significant challenges. Most notably, current analysis methods often yield extensive lists...

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Main Authors: Efrat Muller, Itamar Shiryan, Elhanan Borenstein
Format: Article
Language:English
Published: Nature Portfolio 2024-03-01
Series:Nature Communications
Online Access:https://doi.org/10.1038/s41467-024-46888-3
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author Efrat Muller
Itamar Shiryan
Elhanan Borenstein
author_facet Efrat Muller
Itamar Shiryan
Elhanan Borenstein
author_sort Efrat Muller
collection DOAJ
description Abstract Multi-omic studies of the human gut microbiome are crucial for understanding its role in disease across multiple functional layers. Nevertheless, integrating and analyzing such complex datasets poses significant challenges. Most notably, current analysis methods often yield extensive lists of disease-associated features (e.g., species, pathways, or metabolites), without capturing the multi-layered structure of the data. Here, we address this challenge by introducing “MintTea”, an intermediate integration-based approach combining canonical correlation analysis extensions, consensus analysis, and an evaluation protocol. MintTea identifies “disease-associated multi-omic modules”, comprising features from multiple omics that shift in concord and that collectively associate with the disease. Applied to diverse cohorts, MintTea captures modules with high predictive power, significant cross-omic correlations, and alignment with known microbiome-disease associations. For example, analyzing samples from a metabolic syndrome study, MintTea identifies a module with serum glutamate- and TCA cycle-related metabolites, along with bacterial species linked to insulin resistance. In another dataset, MintTea identifies a module associated with late-stage colorectal cancer, including Peptostreptococcus and Gemella species and fecal amino acids, in line with these species’ metabolic activity and their coordinated gradual increase with cancer development. This work demonstrates the potential of advanced integration methods in generating systems-level, multifaceted hypotheses underlying microbiome-disease interactions.
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spelling doaj.art-d59ea67ca66e4362b27d3ec3c49e690c2024-03-24T12:25:58ZengNature PortfolioNature Communications2041-17232024-03-0115111310.1038/s41467-024-46888-3Multi-omic integration of microbiome data for identifying disease-associated modulesEfrat Muller0Itamar Shiryan1Elhanan Borenstein2Blavatnik School of Computer Science, Tel Aviv UniversityBlavatnik School of Computer Science, Tel Aviv UniversityBlavatnik School of Computer Science, Tel Aviv UniversityAbstract Multi-omic studies of the human gut microbiome are crucial for understanding its role in disease across multiple functional layers. Nevertheless, integrating and analyzing such complex datasets poses significant challenges. Most notably, current analysis methods often yield extensive lists of disease-associated features (e.g., species, pathways, or metabolites), without capturing the multi-layered structure of the data. Here, we address this challenge by introducing “MintTea”, an intermediate integration-based approach combining canonical correlation analysis extensions, consensus analysis, and an evaluation protocol. MintTea identifies “disease-associated multi-omic modules”, comprising features from multiple omics that shift in concord and that collectively associate with the disease. Applied to diverse cohorts, MintTea captures modules with high predictive power, significant cross-omic correlations, and alignment with known microbiome-disease associations. For example, analyzing samples from a metabolic syndrome study, MintTea identifies a module with serum glutamate- and TCA cycle-related metabolites, along with bacterial species linked to insulin resistance. In another dataset, MintTea identifies a module associated with late-stage colorectal cancer, including Peptostreptococcus and Gemella species and fecal amino acids, in line with these species’ metabolic activity and their coordinated gradual increase with cancer development. This work demonstrates the potential of advanced integration methods in generating systems-level, multifaceted hypotheses underlying microbiome-disease interactions.https://doi.org/10.1038/s41467-024-46888-3
spellingShingle Efrat Muller
Itamar Shiryan
Elhanan Borenstein
Multi-omic integration of microbiome data for identifying disease-associated modules
Nature Communications
title Multi-omic integration of microbiome data for identifying disease-associated modules
title_full Multi-omic integration of microbiome data for identifying disease-associated modules
title_fullStr Multi-omic integration of microbiome data for identifying disease-associated modules
title_full_unstemmed Multi-omic integration of microbiome data for identifying disease-associated modules
title_short Multi-omic integration of microbiome data for identifying disease-associated modules
title_sort multi omic integration of microbiome data for identifying disease associated modules
url https://doi.org/10.1038/s41467-024-46888-3
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