XhetRel: A Pipeline for X Heterozygosity and Relatedness Analysis in Sequencing Data

Motivation Checking sample sex is one of the preliminary controls performed in genetic studies. Comparing multiple individuals and families in terms of sex and relatedness allows us to eliminate systematic errors in downstream analyses. While developing the pipeline we further delved into the origins of X heterozygosity by analysing the chromosome X variants from the 1000 Genomes Project. Result We created an accessible and user-friendly notebook application for X heterozygosity analysis. XhetRel can serve as an initial quality control step in sequencing projects. Further investigating the source of X heterozygosity reveals the limitations of sequencing and variant calling methods in heterozygosity analysis. Our findings point to specific pseudogenes and gene clusters, such as SLC25A5 and GAGE cluster, as key contributors to erroneous variant allele fractions. Availability and implementation Source code is available https://github.com/barslmn/XhetRel . Collab notebook can be accessed at https://colab.research.google.com/drive/1ep69JvXLwK5ndHUQ8qIGTWvauzsTW9fi .