BinDel: Detecting Clinically Relevant Fetal Genomic Microdeletions Using Low‐Coverage Whole‐Genome Sequencing‐Based NIPT

ABSTRACT Objective Clinically pathogenic chromosomal microdeletions cause severe genetic disorders. Motivated by the absence of reliable screening of microdeletions during the first‐trimester screening, we developed BinDel, a software tool to determine the risk of clinically relevant pathogenic fetal microdeletions from low‐coverage whole‐genome‐sequencing (WGS) based NIPT data. Methods We developed novel computational software that employs a targeted approach with region‐specific normalisation and calling procedures to detect microdeletion risk in predefined chromosomal regions. The software was developed using 500 NIPT samples and validated on an additional 84 samples, including 34 rare fetal microdeletions confirmed both pre‐ and postnatally. Results BinDel correctly identified 30 out of 34 samples with microdeletions, with only three false‐positive calls among 50 euploid samples, all latter originating from the Williams‐Beuren and Prader‐Willi/Angelman syndrome‐associated microdeletion regions. Conclusions We confirmed BinDel's feasibility for integrating microdeletion analysis into routine NIPT protocol. This work stands as a unique contribution to prenatal microdeletion screening, providing a novel and readily available software tool that was validated with a large set of actual microdeletion samples, positioning it as the first of its kind in the field. BinDel is available at https://github.com/seqinfo/BinDel .