Homo sapiens Genome sequencing and assembly. Homo sapiens

The whole genome karyotype refers to the sequence of large chromosomal segments that make upan individuals genotype. karyotype analysis, which includes descriptions of aneuploidies and otherrearrangements is crucial for understanding genetic risk factors, for diagnosis, treatment decisions,and genetic counseling linked to constitutional disorders. The current karyotyping standard isbased on microscopic examination of chromosomes, a complex process that requires high expertiseand offers Mb scale resolution.Optical Genome Mapping (OGM) technology can identify large DNA lesions in a cost-effectivemanner. In this paper, we developed OMKar, a method that uses OGM data to create a virtualkaryotype. OMKar processes Structural (SV) and Copy Number (CN) Variants as inputs andencodes them into a compact breakpoint graph. It recomputes copy numbers using Integer LinearProgramming to maintain CN balance and then identifies constrained Eulerian paths representingentire donor chromosomes. In tests using 38 whole genome simulations of constitutional disorders,OMKar reconstructed the karyotype with 88% precision and 95% recall on SV concordance and95% Jaccard score on CN concordance. We applied OMKar to 50 prenatal, 41 postnatal, and63 parental samples from ten different sites. OMKar reconstructed the correct karyotype in 144out of 154 samples, covering 25 of 25 aneuploidies, 32 of 32 balanced translocations, and 72 of 82unbalanced variations. Detected constitutional disorders included Cri-du-chat, Wolf-Hirschhorn,Prader-Willi deletions, Down, and Turner syndromes. Importantly, it identified a plausible geneticmechanism for five cases of constitutional disorder that were not detected by other technologies.Together, these results demonstrate the robustness of OMKar for OGM-based karyotyping