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bioRxiv · 10.1101/2020.12.18.423378

A Framework to Analyse and Interpret Mouse Functional Genome by Prioritizing High Impact SNPs

Arslan, A.
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Abstract

The essential understanding of disease pathogenesis and enabling genetic findings to be used for developing new therapeutics, is missing in the identifications of genomic loci through whole genome association studies (GWAS). Here we describe a new computational method (mMap) that reduces this gap by characterizing the functional and regulatory impact of allelic variation. The method incorporates the precomputed annotations of 26 protein functional regions and eight regulatory regions and recover SNPs that fall/lie in these regions. After annotating SNPs to functional or regulatory data, method link them to biological functions and pathways, and predicts significantly disrupted biological regions, processes and pathways, by controlling false discovery through hypergeometric test. By doing so, the method limits data to human interpretation level by prioritizing SNPs that have the potential to mediate a biological phenotype. The method is applicable to procedures that rely on the understanding of the biological causal role of mouse SNPs and is available online. In two example mMap applications, including whole genomes SNPs data from 48 inbred mice strains, we identify biological mechanisms by which SNPs can regulate pathways to govern phenotypes by targeting different coding and regulatory regions, even in closely related strains.

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Arslan, A.. 2020-12-19. A Framework to Analyse and Interpret Mouse Functional Genome by Prioritizing High Impact SNPs. https://doi.org/10.1101/2020.12.18.423378

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