HemoMIPs—Automated analysis and result reporting pipeline for targeted sequencing data

Targeted sequencing of genomic regions is a cost- and time-efficient approach for screening patient cohorts. We present a fast and efficient workflow to analyze highly imbalanced, targeted next-generation sequencing data generated using molecular inversion probe (MIP) capture. Our Snakemake pipeline performs sample demultiplexing, overlap paired-end merging, alignment, MIP-arm trimming, variant calling, coverage analysis and report generation. Further, we support the analysis of probes specifically designed to capture certain structural variants and can assign sex using Y-chromosome-unique probes. In a user-friendly HTML report, we summarize all these results including covered, incomplete or missing regions, called variants and their predicted effects. We developed and tested our pipeline using the hemophilia A & B MIP design from the “My Life, Our Future” initiative. HemoMIPs is available as an open-source tool on GitHub at: https://github.com/kircherlab/hemoMIPsAuthor summary: Next generation sequencing techniques enable researchers to identify causal variants for patients in large cohorts. Targeted sequencing approaches capture genomic regions of interest to allow high throughput and cost efficient patient-specific data generation. HemoMIPs is an open-source software that analyses targeted sequencing datasets generated using molecular inversion probes (MIPs) and provides HTML reports of pathogenic and benign variants, patient sex, existence of known structural variants as well as performance statistics on the sequencing run.