CytoGPS: A large-scale karyotype analysis of CML data

Karyotyping, the practice of visually examining and recording chromosomal abnormalities, is commonly used to diagnose diseases of genetic origin, including cancers. Karyotypes are recorded as text written in the International System for Human Cytogenetic Nomenclature (ISCN). Downstream analysis of karyotypes is conducted manually, due to the visual nature of analysis and the linguistic structure of the ISCN. The ISCN has not been computer-readable and, as such, prevents the full potential of these genomic data from being realized. In response, we developed CytoGPS, a platform to analyze large volumes of cytogenetic data using a Loss-Gain-Fusion model that converts the human-readable ISCN karyotypes into a machine-readable binary format. As proof of principle, we applied CytoGPS to cytogenetic data from the Mitelman Database of Chromosome Aberrations and Gene Fusions in Cancer, a National Cancer Institute hosted database of over 69,000 karyotypes of human cancers. Using the Jaccard coefficient to determine similarity between karyotypes structured as binary vectors, we were able to identify novel patterns from 4,968 Mitelman CML karyotypes, such as the co-occurrence of trisomy 19 and 21. The CytoGPS platform unlocks the potential for large-scale, comparative analysis of cytogenetic data. This methodological platform is freely available at CytoGPS.org.