GRAPE: genomic relatedness detection pipeline [version 2; peer review: 2 approved]

Abstract

Classifying the degree of relatedness between pairs of individuals has both scientific and commercial applications. As an example, genome-wide association studies (GWAS) may suffer from high rates of false positive results due to unrecognized population structure. This problem becomes especially relevant with recent increases in large-cohort studies. Accurate relationship classification is also required for genetic linkage analysis to identify disease-associated loci. Additionally, DNA relatives matching service is one of the leading drivers for the direct-to-consumer genetic testing market. Despite the availability of scientific and research information on the methods for determining kinship and the accessibility of relevant tools, the assembly of the pipeline, which stably operates on a real-world genotypic data, requires significant research and development resources. Currently, there is no open source end-to-end solution for relatedness detection in genomic data, that is fast, reliable and accurate for both close and distant degrees of kinship, combines all the necessary processing steps to work on a real data, and is ready for production integration. To address this, we developed GRAPE: Genomic RelAtedness detection PipelinE. It combines data preprocessing, identity-by-descent (IBD) segments detection, and accurate relationship estimation. The project uses software development best practices, as well as Global Alliance for Genomics and Health (GA4GH) standards and tools. Pipeline efficiency is demonstrated on both simulated and real-world datasets. GRAPE is available from: https://github.com/genxnetwork/grape.

Keywords

• kinship and relationship estimation
• identity-by-descent
• snakemake workflow
• bioinformatics pipeline
• phasing and imputation
• sequencing data
• eng