PWAS: proteome-wide association study-linking genes and phenotypes by functional variation in proteins

We introduce Proteome-Wide Association Study (PWAS), a new method for detecting gene-phenotype associations mediated by protein function alterations. PWAS aggregates the signal of all variants jointly affecting a protein-coding gene and assesses their overall impact on the protein's function us...

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Bibliographic Details
Published in:Genome Biology 2020-07, Vol.21 (1), p.173-173, Article 173
Main Authors: Brandes, Nadav, Linial, Nathan, Linial, Michal
Format: Article
Language:English
Subjects:
Case studies
Colorectal cancer
Gene expression
Gene loci
Genomes
Genotype & phenotype
GWAS
Heredity
Heritability
Learning algorithms
Machine learning
Method
Methods
Noise
Phenotypes
Phenotypic variations
Protein annotations
Protein function
Proteins
Proteomes
Recessive heritability
Simulation
UK Biobank
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Summary:We introduce Proteome-Wide Association Study (PWAS), a new method for detecting gene-phenotype associations mediated by protein function alterations. PWAS aggregates the signal of all variants jointly affecting a protein-coding gene and assesses their overall impact on the protein's function using machine learning and probabilistic models. Subsequently, it tests whether the gene exhibits functional variability between individuals that correlates with the phenotype of interest. PWAS can capture complex modes of heritability, including recessive inheritance. A comparison with GWAS and other existing methods proves its capacity to recover causal protein-coding genes and highlight new associations. PWAS is available as a command-line tool.
ISSN:1474-760X
1474-7596
1474-760X
DOI:10.1186/s13059-020-02089-x