DEVOUR: Deleterious Variants on Uncovered Regions in Whole-Exome Sequencing

Erdem Türk; Akif Ayaz; Ayhan Yüksek; Barış E Süzek

doi:10.7717/peerj.16026

DEVOUR: Deleterious Variants on Uncovered Regions in Whole-Exome Sequencing

PeerJ. 2023 Sep 15:11:e16026. doi: 10.7717/peerj.16026. eCollection 2023.

Authors

Erdem Türk^{1

2}, Akif Ayaz³, Ayhan Yüksek¹, Barış E Süzek^{1

2}

Affiliations

¹ Department of Computer Engineering, Muğla Sıtkı Koçman University, Muğla, Turkey.
² Bioinformatics Graduate Program, Muğla Sıtkı Koçman University, Muğla, Turkey.
³ Department of Medical Genetics, School of Medicine, İstanbul Medipol University, İstanbul, Turkey.

Abstract

The discovery of low-coverage (i.e. uncovered) regions containing clinically significant variants, especially when they are related to the patient's clinical phenotype, is critical for whole-exome sequencing (WES) based clinical diagnosis. Therefore, it is essential to develop tools to identify the existence of clinically important variants in low-coverage regions. Here, we introduce a desktop application, namely DEVOUR (DEleterious Variants On Uncovered Regions), that analyzes read alignments for WES experiments, identifies genomic regions with no or low-coverage (read depth < 5) and then annotates known variants in the low-coverage regions using clinical variant annotation databases. As a proof of concept, DEVOUR was used to analyze a total of 28 samples from a publicly available Hirschsprung disease-related WES project (NCBI Bioproject: https://www.ncbi.nlm.nih.gov/bioproject/?term=PRJEB19327), revealing the potential existence of 98 disease-associated variants in low-coverage regions. DEVOUR is available from https://github.com/projectDevour/DEVOUR under the MIT license.

Keywords: Clinical NGS informatics; Genetic diseases; Genetic disposition to disease; Genetic variants; Medical genetics; Next-generation sequence (NGS) analysis; Whole-exome sequencing (WES) analysis.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Databases, Factual
Existentialism*
Exome Sequencing
Genomics
Hirschsprung Disease* / diagnosis
Humans

Grants and funding

This work was supported by the Scientific and Technological Research Council of Turkey (No. 120E522). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.