OBJECTIVE ANALYSIS OF CHROMOSOME BANDING PATTERNS

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This project aims to develop and commercialize significantly improved computer software for chromosome band pattern analysis and anomaly detection. Used on modern computerized chromosome analysis instruments, this will allow objective characterization and convenient display of chromosome banding patterns, and quantitative comparison of chromosomes to normal and abnormal prototypes and to each other. This will help cytogeneticists detect and quantify sub- visible band pattern alterations, particularly with high resolution banding. It will significantly increase the ability of automated chromosome analysis instruments to evaluate chromosome alterations in normal and neoplastic mammalian cells. Specifically, we use frequency domain eigenanalysis, an image analysis technique developed at the Baylor College of Medicine, to decompose chromosome images into components, automatically selecting out relevant characteristics of the banding pattern while eliminating components that reflect preparatory artifact, inter-chromosome variation, and other irrelevant differences. During the Phase I project we implemented a set of eigenanalysis techniques on the PSII system, and we developed one new technique, single chromosome eigenanalysis. We demonstrated improved chromosome classification accuracy and objective chromosome prototype generation. In Phase II we will test and qualify these on several cytogenetic applications of eigenanalysis, using it to: (1) construct prototypes of normal chromosomes, (2) assist interactive karyotyping by displaying normal chromosome prototypes, (3) improve chromosome classification accuracy, (4) construct prototypes of specific chromosomal abnormalities, (5) automatically detect specific abnormalities such as translocations, (6) point out localized differences in homologs, (7) determine the condensation state of chromosomes, (8) characterize different condensation stages, and (9) develop prototypical chromosome images for patient groups manifesting genetically linked diseases. We will implement successful applications on PSII's PowerGene commercial automatic karyotyping workstation. PROPOSED COMMERCIAL APPLICATIONS As soon as the applications are developed and qualified for routine application, they will be incorporated into PSII's PowerGene products, both in new systems sold and as an upgrade to existing systems.