Leveraging multiple genomic data to prioritize disease-causing indels from exome sequencing data

Scientific Reports
Mengmeng WuRui Jiang

Abstract

The emergence of exome sequencing in recent years has enabled rapid and cost-effective detection of genetic variants in coding regions and offers a great opportunity to combine sequencing experiments with subsequent computational analysis for dissecting genetic basis of human inherited diseases. However, this strategy, though successful in practice, still faces such challenges as limited sample size and substantial number or diversity of candidate variants. To overcome these obstacles, researchers have been concentrated in the development of advanced computational methods and have recently achieved great progress for analysing single nucleotide variant. Nevertheless, it still remains unclear on how to analyse indels, another type of genetic variant that accounts for substantial proportion of known disease-causing variants. In this paper, we proposed an integrative method to effectively identify disease-causing indels from exome sequencing data. Specifically, we put forward a statistical method to combine five functional prediction scores, four genic association scores and a genic intolerance score to produce an integrated p-value, which could then be used for prioritizing candidate indels. We performed extensive simulation stud...Continue Reading

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Citations

Jun 28, 2020·Briefings in Bioinformatics·Zhenyu YueJunfeng Xia

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Methods Mentioned

BETA
dissect
exome sequencing

Software Mentioned

VEST
OMIM
Ensemble
BioMart
SIFT
PinPor
gexp
CADD
MATCH
ANNOVAR

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