biostudies-literatureUnknown3(2)Verrou KMWhole Exome Sequencing (WES) is used for querying DNA variants using the protein coding parts of genomes (exomes). However, WES analysis can be challenging because of the complexity of the data. Here, we describe a consolidated protocol for unbiased WES analysis. The protocol uses three variant callers (HaplotypeCaller, FreeBayes, and DeepVariant), which have different underlying models. We provide detailed execution steps, as well as basic variant filtering, annotation, visualization, and consolidation aspects.STAR protocols101418https://www.ebi.ac.uk/biostudies/studies/S-EPMC9163752biostudies-literatureProtocol for unbiased, consolidated variant calling from whole exome sequencing data.PMC9163752Moulos PVerrou KMPavlopoulos GAfalseProtocol for unbiased, consolidated variant calling from whole exome sequencing data.Whole Exome Sequencing (WES) is used for querying DNA variants using the protein coding parts of genomes (exomes). However, WES analysis can be challenging because of the complexity of the data. Here, we describe a consolidated protocol for unbiased WES analysis. The protocol uses three variant callers (HaplotypeCaller, FreeBayes, and DeepVariant), which have different underlying models. We provide detailed execution steps, as well as basic variant filtering, annotation, visualization, and consolidation aspects.2022-01-01T00:00:00Z2022 Jun2025-04-20T03:06:10.881Z2025-02-19T04:04:50.824ZS-EPMC91637523566905010.1016/j.xpro.2022.101418