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Cited by 12Bioinformatics and Genomic NetworksGenetic Associations and EpidemiologyGenetic Mapping and Diversity in Plants and Animals

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Organization of gene programs revealed by unsupervised analysis of diverse gene–trait associations

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Mizikovsky, Dalia, Naval Sanchez, Marina, Nefzger, Christian M, Cuellar Partida, Gabriel, Palpant, Nathan J·2022·Nucleic Acids Research
DOI 10.1093/nar/gkac413PMC PMC9410900

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Abstract

Genome wide association studies provide statistical measures of gene–trait associations that reveal how genetic variation influences phenotypes. This study develops an unsupervised dimensionality reduction method called UnTANGLeD (Unsupervised Trait Analysis of Networks from Gene Level Data) which organizes 16,849 genes into discrete gene programs by measuring the statistical association between genetic variants and 1,393 diverse complex traits. UnTANGLeD reveals 173 gene clusters enriched for protein–protein interactions and highly distinct biological processes governing development, signalling, disease, and homeostasis. We identify diverse gene networks with robust interactions but not associated with known biological processes. Analysis of independent disease traits shows that UnTANGLeD gene clusters are conserved across all complex traits, providing a simple and powerful framework to predict novel gene candidates and programs influencing orthogonal disease phenotypes. Collectively, this study demonstrates that gene programs co-ordinately orchestrating cell functions can be identified without reliance on prior knowledge, providing a method for use in functional annotation, hypothesis generation, machine learning and prediction algorithms, and the interpretation of diverse genomic data.

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Metadata

Authors
Mizikovsky, D., Naval Sanchez, M., Nefzger, C. M., Cuellar Partida, G., & Palpant, N. J.
Affiliations
  • The University of Queensland (AU)
  • Institute for Molecular Bioscience, University of Queensland , Brisbane, QLD, Australia
  • University of Queensland, Diamantina Institute, Brisbane, QLD ,  Australia
Corresponding author
Palpant, Nathan J
ORCID
Venue
Nucleic Acids Research
Publisher
Oxford University Press (OUP)
Published
2022-06-18
Volume
50
Issue
15
Pages
e87-e87
ISSN
  • 0305-1048 (ISSN-L)
  • 1362-4962
DOI
10.1093/nar/gkac413
PMC
PMC9410900
OpenAlex
W4283123298
Cited by
12
References
5
Citations by year
2026: 4 · 2025: 2 · 2024: 1 · 2023: 4 · 2022: 1
FWCI
0.65
Type
journal article
Language
en
Open access
Licence
Locations
  • Nucleic Acids Research (publishedVersion, cc-by-nc)
  • bioRxiv (Cold Spring Harbor Laboratory) (acceptedVersion, cc-by-nc-nd)
  • PubMed Central (publishedVersion, cc-by-nc)
  • PubMed (publishedVersion)
Funders
  • National Health and Medical Research Council (1143163)
  • Australian Research Council (SR1101002)
  • National Heart Foundation of Australia (101889)
Topics
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Bioinformatics and Genomic Networks
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Genetic Associations and Epidemiology
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Genetic Mapping and Diversity in Plants and Animals
Keywords
gene programs, gene clusters, complex traits, genetic variants, unsupervised dimensionality reduction, protein-protein interaction, gene networks, disease phenotypes, functional annotation, gene-trait association
MeSH terms
Disease, Phenotype, Polymorphism, Single Nucleotide, Genomics, Gene Regulatory Networks, Genome-Wide Association Study

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