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Variant calling pipelines for whole exome sequencing in clinical context

Stepanian, J.; Saldana, D.; Mahecha, D.; Mazabel, L.; Diaz, J.

2024-10-19 genetic and genomic medicine
10.1101/2024.10.18.24315708 medRxiv
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1IntroductionWhole exome sequencing (WES) has become a more accessible diagnostic tool in clinical genetic context, leading to the debate of the most accurate and effective bioinformatic pipeline solutions to evaluate variants that explain diseases. ObjectiveThis study aimed to evaluate twenty-four pipelines in two samples comparing accuracy, time and computing efficiency. We also contrasted the results based on regions in two of the most common capture kits. Materials and methodsWe used two accessions of NA12872 whole exome sequencing to contrast four different free access software for mapping using hg38 reference genome, then we used six different software alternatives for variant calling process. Finally, differences in computational resources and efficacy were evaluated. ResultsOur results showed that the most accurate and fastest pipeline is BWA with Strelka for SNVs detection, and differences in the use of resources and efficacy were proven. ConclusionsBWA and Strelka are the most accurate and fastest for detecting SNVs in clinical exomes. Significant differences in efficiency and resource usage exist among the workflows evaluated. These findings aid in selecting the best methods for clinical contexts.

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