TY - GEN
T1 - OMKar
T2 - 29th International Conference on Research in Computational Molecular Biology, RECOMB 2025
AU - Raeisi Dehkordi, Siavash
AU - Jia, Zhaoyang
AU - Estabrook, Joey
AU - Hauenstein, Jen
AU - Miller, Neil
AU - Güleray-Lafci, Naz
AU - Neesen, Jürgen
AU - Hastie, Alex
AU - Pang, Andy Wing Chun
AU - Dremsek, Paul
AU - Bafna, Vineet
N1 - Publisher Copyright:
© The Author(s), under exclusive license to Springer Nature Switzerland AG 2025.
PY - 2025
Y1 - 2025
N2 - The whole genome karyotype represents the sequence of large chromosomal segments that define an individual’s genotype, encompassing variants such as aneuploidies, balanced, and unbalanced translocations. Karyotype analysis is essential for identifying genetic risk factors, guiding diagnoses, and informing treatment and genetic counseling for constitutional disorders. Optical Genome Mapping (OGM) offers a high-resolution alternative to traditional microscopic karyotyping. We present OMKar, an automated tool that leverages OGM data to generate virtual karyotypes by processing structural variants (SVs) and copy number variants (CNVs) into a breakpoint graph. OMKar employs Integer Linear Programming to ensure chromosomal balance and identifies Eulerian paths to reconstruct chromosomes. In simulation tests, OMKar reconstruction achieved 88% precision and 95% recall for SV concordance and a 95% Jaccard score for CNV concordance. It was further validated on 154 clinical samples from ten different sites, where it successfully reconstructed 144 of the 154 karyotypes. OMKar identified genetic mechanisms for five disorders missed by traditional karyotyping, demonstrating its robustness in detecting constitutional disorders. The tool is publicly available at https://github.com/siavashre/OMKar.
AB - The whole genome karyotype represents the sequence of large chromosomal segments that define an individual’s genotype, encompassing variants such as aneuploidies, balanced, and unbalanced translocations. Karyotype analysis is essential for identifying genetic risk factors, guiding diagnoses, and informing treatment and genetic counseling for constitutional disorders. Optical Genome Mapping (OGM) offers a high-resolution alternative to traditional microscopic karyotyping. We present OMKar, an automated tool that leverages OGM data to generate virtual karyotypes by processing structural variants (SVs) and copy number variants (CNVs) into a breakpoint graph. OMKar employs Integer Linear Programming to ensure chromosomal balance and identifies Eulerian paths to reconstruct chromosomes. In simulation tests, OMKar reconstruction achieved 88% precision and 95% recall for SV concordance and a 95% Jaccard score for CNV concordance. It was further validated on 154 clinical samples from ten different sites, where it successfully reconstructed 144 of the 154 karyotypes. OMKar identified genetic mechanisms for five disorders missed by traditional karyotyping, demonstrating its robustness in detecting constitutional disorders. The tool is publicly available at https://github.com/siavashre/OMKar.
KW - Constitutional disease
KW - Karyotyping
KW - Optical Genome Mapping
UR - https://www.scopus.com/pages/publications/105004254684
U2 - 10.1007/978-3-031-90252-9_22
DO - 10.1007/978-3-031-90252-9_22
M3 - Conference contribution
AN - SCOPUS:105004254684
SN - 9783031902512
T3 - Lecture Notes in Computer Science
SP - 281
EP - 284
BT - Research in Computational Molecular Biology - 29th International Conference, RECOMB 2025, Proceedings
A2 - Sankararaman, Sriram
PB - Springer Science and Business Media Deutschland GmbH
Y2 - 26 April 2025 through 29 April 2025
ER -