Automated Identification of Chromosome Segments Involved in Translocations by Combining Spectral Karyotyping and Banding Analysis

Abstract

The identification of chromosome abnormalities is an essential part of diagnosis and treatment of genetic disorders such as chromosomal syndromes and many types of cancer. Modern cytogenetic imaging techniques have improved the study of chromosome aberrations but they are most often used as adjuncts to traditional G-banded karyotype analysis. Molecular cytogenetic techniques such as comparative genomic hybridization, multicolor fluorescence <i xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">in</i> <i xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">situ</i> hybridization, and spectral karyotyping (SKY) are able to detect chromosome copy number changes and complex structural aberrations in cancers, particularly in hematological malignancies and solid tumors. However, banded chromosome analysis is essential to distinguish between normal and abnormal chromosomes. Currently available cytogenetic imaging software is designed to classify only normal chromosomes. The identification of the banded regions involved in the abnormal chromosomes is done manually. In this paper, we propose an algorithm to automate the banding analysis of abnormal chromosomes by comparing the information obtained by SKY for precise identification of translocation break points. Our algorithm is based on the dynamic time warping method in order to overcome the problems due to the nonrigid nature of chromosomes. The method has been implemented and successfully applied to detect chromosome translocations, deletions, and duplications in cell lines derived from solid tumors.