This document briefly outlines the essential steps in the process of making genetic variant calls, and recommends tools that have gained community acceptance for this purpose. It is assumed that the purpose of the study is to detect short germline or somatic variants in a single sample. Recommended coverage for acceptable quality of calls in a research setting is around 30-50x for whole genome and 70-100x for exome sequencing, but lower coverage is discussed as well.
The procedures outlined below are recommendations to the H3ABioNet groups planning to do variant calling on human genome data, and are not meant to be prescriptive. Our goal is to help the groups set up their procedures and workflows, and to provide an overview of the main steps involved and the tools that can be used to implement them. For optimizing a workflow or an individual analysis step, the reader is referred to 1,2,3.
Laurie, S. et al. From Wet-Lab to Variations: Concordance and Speed of Bioinformatics Pipelines for Whole Genome and Whole Exome Sequencing. Hum. Mutat. 37, 1263–1271 (2016). ↩
Hwang, S., Kim, E., Lee, I. & Marcotte, E. M. Systematic comparison of variant calling pipelines using gold standard personal exome variants. Sci. Rep. 5, 17875 (2015). ↩
This work is licensed under a Creative Commons Attribution-NonCommercial-ShareAlike 4.0 International License.