OMKar: optical map based automated karyotyping of genomes to identify constitutional abnormalities

medRxiv (Cold Spring Harbor Laboratory), Journal Year: 2025, Volume and Issue: unknown

Published: Feb. 14, 2025

The whole genome karyotype refers to the sequence of large chromosomal segments that make up an individual's genotype. analysis, which includes descriptions aneuploidies and other rearrangements is crucial for understanding genetic risk factors, diagnosis, treatment decisions, counseling linked constitutional disorders. current karyotyping standard based on microscopic examination chromosomes, a complex process requires high expertise offers Mb scale resolution. Optical Genome Mapping (OGM) technology can identify DNA lesions in cost-effective manner. In this paper, we developed OMKar, method uses OGM data create virtual karyotype. OMKar processes Structural (SV) Copy Number (CN) Variants as inputs encodes them into compact breakpoint graph. It recomputes copy numbers using Integer Linear Programming maintain CN balance then identifies constrained Eulerian paths representing entire donor chromosomes. tests 38 simulations disorders, reconstructed with 88% precision 95% recall SV concordance Jaccard score concordance. We applied 50 prenatal, 41 postnatal, 63 parental samples from ten different sites. correct 144 out 154 samples, covering 25 aneuploidies, 32 balanced translocations, 72 82 unbalanced variations. Detected disorders included Cri-du-chat, Wolf-Hirschhorn, Prader-Willi deletions, Down, Turner syndromes. Importantly, it identified plausible mechanism five cases disorder were not detected by technologies. Together, these results demonstrate robustness OGM-based karyotyping. publicly available at https://github.com/siavashre/OMKar .

Language: Английский

Osteosarcoma

Surgical pathology clinics, Journal Year: 2025, Volume and Issue: unknown

Published: March 1, 2025