Melody: meta-analysis of microbiome association studies for discovering generalizable microbial signatures

Abstract Standard protocols for meta-analysis of association studies are inadequate for microbiome data due to their complex compositional structure, leading to inaccurate and unstable microbial signature selection. To address this issue, we introduce Melody, a framework that generates, harmonizes,...

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Main Authors: Zhoujingpeng Wei, Guanhua Chen, Zheng-Zheng Tang
Format: Article
Language:English
Published: BMC 2025-08-01
Series:Genome Biology
Subjects:
Online Access:https://doi.org/10.1186/s13059-025-03721-4
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author Zhoujingpeng Wei
Guanhua Chen
Zheng-Zheng Tang
author_facet Zhoujingpeng Wei
Guanhua Chen
Zheng-Zheng Tang
author_sort Zhoujingpeng Wei
collection DOAJ
description Abstract Standard protocols for meta-analysis of association studies are inadequate for microbiome data due to their complex compositional structure, leading to inaccurate and unstable microbial signature selection. To address this issue, we introduce Melody, a framework that generates, harmonizes, and combines study-specific summary association statistics to powerfully and robustly identify microbial signatures in meta-analysis. Comprehensive and realistic simulations demonstrate that Melody substantially outperforms existing approaches in prioritizing true signatures. In the meta-analyses of five studies on colorectal cancer and eight studies on the gut metabolome, we showcase the superior stability, reliability, and predictive performance of Melody-identified signatures.
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institution DOAJ
issn 1474-760X
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publishDate 2025-08-01
publisher BMC
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series Genome Biology
spelling doaj-art-939bb7b894824bcfa8a2fda5ff0184a62025-08-20T03:07:25ZengBMCGenome Biology1474-760X2025-08-0126112010.1186/s13059-025-03721-4Melody: meta-analysis of microbiome association studies for discovering generalizable microbial signaturesZhoujingpeng Wei0Guanhua Chen1Zheng-Zheng Tang2Department of Biostatistics and Medical Informatics, University of Wisconsin-MadisonDepartment of Biostatistics and Medical Informatics, University of Wisconsin-MadisonDepartment of Biostatistics and Medical Informatics, University of Wisconsin-MadisonAbstract Standard protocols for meta-analysis of association studies are inadequate for microbiome data due to their complex compositional structure, leading to inaccurate and unstable microbial signature selection. To address this issue, we introduce Melody, a framework that generates, harmonizes, and combines study-specific summary association statistics to powerfully and robustly identify microbial signatures in meta-analysis. Comprehensive and realistic simulations demonstrate that Melody substantially outperforms existing approaches in prioritizing true signatures. In the meta-analyses of five studies on colorectal cancer and eight studies on the gut metabolome, we showcase the superior stability, reliability, and predictive performance of Melody-identified signatures.https://doi.org/10.1186/s13059-025-03721-4Absolute abundanceBest subset selectionCompositional dataMeta-analysisQuasi-multinomial modelRelative abundance
spellingShingle Zhoujingpeng Wei
Guanhua Chen
Zheng-Zheng Tang
Melody: meta-analysis of microbiome association studies for discovering generalizable microbial signatures
Genome Biology
Absolute abundance
Best subset selection
Compositional data
Meta-analysis
Quasi-multinomial model
Relative abundance
title Melody: meta-analysis of microbiome association studies for discovering generalizable microbial signatures
title_full Melody: meta-analysis of microbiome association studies for discovering generalizable microbial signatures
title_fullStr Melody: meta-analysis of microbiome association studies for discovering generalizable microbial signatures
title_full_unstemmed Melody: meta-analysis of microbiome association studies for discovering generalizable microbial signatures
title_short Melody: meta-analysis of microbiome association studies for discovering generalizable microbial signatures
title_sort melody meta analysis of microbiome association studies for discovering generalizable microbial signatures
topic Absolute abundance
Best subset selection
Compositional data
Meta-analysis
Quasi-multinomial model
Relative abundance
url https://doi.org/10.1186/s13059-025-03721-4
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AT guanhuachen melodymetaanalysisofmicrobiomeassociationstudiesfordiscoveringgeneralizablemicrobialsignatures
AT zhengzhengtang melodymetaanalysisofmicrobiomeassociationstudiesfordiscoveringgeneralizablemicrobialsignatures