Evidence map›Paper›PMID 34784344›Full record

ArticlePLoS computational biology2021

Multivariable association discovery in population-scale meta-omics studies.

Himel Mallick, Ali Rahnavard, Lauren J McIver, Siyuan Ma, Yancong Zhang, Long H Nguyen, Timothy L Tickle, George Weingart, Boyu Ren, Emma H Schwager and 10 more

Abstract read
In one paragraph

Article in PLoS computational biology, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 1,741 papers.

0numbers the graph read from it
0cells of the map it votes in
1,741citing papers in PubMed
–field-weighted citation impact
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

1,741 citing papers in PubMed.

  1. Trial
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  5. Testosterone administration partially modulates gut microbiota responses to severe energy deficit.American journal of physiology. Endocrinology and metabolism · 2026
    Trial
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  9. Article
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  13. Immunoglobulin A protease fromGut microbes · 2026
    Article
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  16. Article
  17. Article
  18. Article
  19. Gut microbes · 2026
    Article
  20. Article

1,681 more citing papers are in PubMed but not listed here.

4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

20 authors.

Himel MallickBiostatistics Department, Harvard T. H. Chan School of Public Health, Boston, Massachusetts, United States of America.ORCID 0000-0003-4956-2429
Ali RahnavardComputational Biology Institute, Department of Biostatistics and Bioinformatics, Milken Institute School of Public Health, George Washington University, Washington DC, United States of America.ORCID 0000-0002-9710-0248
Lauren J McIverBiostatistics Department, Harvard T. H. Chan School of Public Health, Boston, Massachusetts, United States of America.ORCID 0000-0002-2199-4310
Siyuan MaBiostatistics Department, Harvard T. H. Chan School of Public Health, Boston, Massachusetts, United States of America.ORCID 0000-0003-2313-6448
Yancong ZhangBiostatistics Department, Harvard T. H. Chan School of Public Health, Boston, Massachusetts, United States of America.ORCID 0000-0002-2768-2975
Long H NguyenBiostatistics Department, Harvard T. H. Chan School of Public Health, Boston, Massachusetts, United States of America.ORCID 0000-0002-5436-4219
Timothy L TickleThe Broad Institute, Cambridge, Massachusetts, United States of America.ORCID 0000-0002-6592-6272
George WeingartBiostatistics Department, Harvard T. H. Chan School of Public Health, Boston, Massachusetts, United States of America.
Boyu RenBiostatistics Department, Harvard T. H. Chan School of Public Health, Boston, Massachusetts, United States of America.ORCID 0000-0002-5300-1184
Emma H SchwagerBiostatistics Department, Harvard T. H. Chan School of Public Health, Boston, Massachusetts, United States of America.ORCID 0000-0002-7385-8994
Suvo ChatterjeeEpidemiology Branch, Division of Intramural Population Health Research, Eunice Kennedy Shriver National Institute of Child Health and Human Development, National Institutes of Health, Bethesda, Maryland, United States of America.
Kelsey N ThompsonBiostatistics Department, Harvard T. H. Chan School of Public Health, Boston, Massachusetts, United States of America.ORCID 0000-0002-9437-9722
Jeremy E WilkinsonBiostatistics Department, Harvard T. H. Chan School of Public Health, Boston, Massachusetts, United States of America.ORCID 0000-0002-8024-5600
Ayshwarya SubramanianBiostatistics Department, Harvard T. H. Chan School of Public Health, Boston, Massachusetts, United States of America.ORCID 0000-0002-4134-7612
Yiren LuBiostatistics Department, Harvard T. H. Chan School of Public Health, Boston, Massachusetts, United States of America.
Levi WaldronDepartment of Epidemiology and Biostatistics, CUNY School of Public Health, New York City, New York, United States of America.ORCID 0000-0003-2725-0694
Joseph N PaulsonDepartment of Biostatistics, Product Development, Genentech, Inc., South San Francisco, California, United States of America.ORCID 0000-0001-8221-7139
Eric A FranzosaBiostatistics Department, Harvard T. H. Chan School of Public Health, Boston, Massachusetts, United States of America.ORCID 0000-0002-8798-7068
Hector Corrada BravoCenter for Bioinformatics and Computational Biology, University of Maryland, College Park, Maryland, United States of America.
Curtis HuttenhowerBiostatistics Department, Harvard T. H. Chan School of Public Health, Boston, Massachusetts, United States of America.ORCID 0000-0002-1110-0096

Funding

Technology CoreU19AI110820 · NIAID · UNIVERSITY OF MARYLAND BALTIMORE · PI WHITE, OWEN R · 2014 to 2023
$36.5M
Pilot & Feasibility ProgramP30DK043351 · NIDDK · MASSACHUSETTS GENERAL HOSPITAL · PI RAYMOND T CHUNG · 1991 to 2026
$35.3M
Characterizing the gut microbial ecosystem for diagnosis and therapy in IBDU54DK102557 · NIDDK · BROAD INSTITUTE, INC. · PI HUTTENHOWER, CURTIS, XAVIER, RAMNIK J · 2014 to 2015
$7.7M
A comprehensive platform for novel therapy development from the microbiomeR24DK110499 · NIDDK · BROAD INSTITUTE, INC. · PI HUTTENHOWER, CURTIS · 2017 to 2021
$7.7M
Overcoming bias and unwanted variability in next generation sequencingR01HG005220 · NHGRI · JOHNS HOPKINS UNIVERSITY · PI IRIZARRY, RAFAEL ANGEL · 2010 to 2018
$3.6M
NHGRI NIH HHS R01 HG005220NIAID NIH HHS U19 AI110820NIDDK NIH HHS P30 DK043351NIDDK NIH HHS R24 DK110499NIDDK NIH HHS U54 DK102557
6 · The paper itself

Abstract

It is challenging to associate features such as human health outcomes, diet, environmental conditions, or other metadata to microbial community measurements, due in part to their quantitative properties. Microbiome multi-omics are typically noisy, sparse (zero-inflated), high-dimensional, extremely non-normal, and often in the form of count or compositional measurements. Here we introduce an optimized combination of novel and established methodology to assess multivariable association of microbial community features with complex metadata in population-scale observational studies. Our approach, MaAsLin 2 (Microbiome Multivariable Associations with Linear Models), uses generalized linear and mixed models to accommodate a wide variety of modern epidemiological studies, including cross-sectional and longitudinal designs, as well as a variety of data types (e.g., counts and relative abundances) with or without covariates and repeated measurements. To construct this method, we conducted a large-scale evaluation of a broad range of scenarios under which straightforward identification of meta-omics associations can be challenging. These simulation studies reveal that MaAsLin 2's linear model preserves statistical power in the presence of repeated measures and multiple covariates, while accounting for the nuances of meta-omics features and controlling false discovery. We also applied MaAsLin 2 to a microbial multi-omics dataset from the Integrative Human Microbiome (HMP2) project which, in addition to reproducing established results, revealed a unique, integrated landscape of inflammatory bowel diseases (IBD) across multiple time points and omics profiles.

Indexed as

Computational BiologyGastrointestinal MicrobiomeMultivariate AnalysisComputer SimulationHumansInflammatory Bowel Diseases

Identifiers

PMID34784344
PMCPMC8714082

What OpenQuestion holds

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Registered trials

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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.