Harnessing omics big data in nine vertebrate species by genome-wide prioritization of sequence variants with the highest predicted deleterious effect on protein function

Rozman, Vita (author), Kunej, Tanja (author)

Harnessing the genomics big data requires innovation in how we extract and interpret biologically relevant variants. Currently, there is no established catalog of prioritized missense variants associated with deleterious protein function phenotypes. We report in this study, to the best of our knowledge, the first genome-wide prioritization of sequence variants with the most deleterious effect on protein function (potentially deleterious variants [pDelVars]) in nine vertebrate species: human, cattle, horse, sheep, pig, dog, rat, mouse, and zebrafish.The analysis was conducted using the Ensembl/BioMart tool. Genes comprising pDelVars in the highest number of examined species were identified using a Python script. Multiple genomic alignments of the selected genes were built to identify interspecies orthologous potentially deleterious variants, which we defined as the ‘‘ortho-pDelVars.’’ Genome-wide prioritization revealed that in humans, 0.12% of the known variants are predicted to be deleterious. In seven out of nine examined vertebrate species, the genes encoding the multiple PDZ domain crumbs cell polarity complex component (MPDZ) and the transforming acidic coiled-coil containing protein 2 (TACC2) comprise pDelVars. Five interspecies ortho-pDelVars were identified in three genes.These findings offer new ways to harness genomics big data by facilitating the identification of functional polymorphisms in humans and animal models and thus provide a future basis for optimization of protocols for whole genome prioritization of pDelVars and screening of orthologous sequence variants. The approach presented here can inform various postgenomic applications such as personalized medicine and multiomics study of health interventions (iatromics).

• Language: English
• Keywords: big data, potentially deleterious variants (pDelVars), orthologous potentially deleterious variants (ortho-pDelVars), PolyPhen (polymorphism phenotyping), SIFT (sorts intolerant from tolerant), single-nucleotide polymorphism (SNP)
• Work type: Article
• Typology: 1.01 - Original Scientific Article
• Organization: BF - Biotechnical Faculty
• Publication status: Published
• Publication version: Author Accepted Manuscript
• Year: 2018
• Number of pages: Str. 410-421
• Numbering: Vol. 22, no. 6
• PID: 20.500.12556/RUL-133071
• UDC: 575
• ISSN on article: 1536-2310
• DOI: 10.1089/omi.2018.0046
• COBISS.SI-ID: 4072584
• Publication date in RUL: 10.11.2021

Record is a part of a journal

• Title: Omics. a ǂjournal of integrative biology
• Shortened title: Omics
• Publisher: Mary Ann Liebert
• ISSN: 1536-2310
• COBISS.SI-ID: 512299289

Secondary language

• Language: Slovenian
• Keywords: genetika, genomika, bioinformatika, baze podatkov, proteini, vretenčarji

Projects

• Funder: ARRS - Slovenian Research Agency
• Project number: P4-0220
• Name: Primerjalna genomika in genomska biodiverziteta