IMPROVED CLASSIFIERS FOR AUTOMATED MULTIPLEX FISH

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DESCRIPTION (Abstract, from the application): Automated karyotyping is an important procedure in cytogenetics labs worldwide. Multiplex fluorescence in situ hybridization (M-FISH) is a recent development that uses multicolor chromosome painting probes and multispectral image analysis to identify subtle and complex chromosomal rearrangements. It promises to make automated karyotyping faster, more accurate, and easier to interpret both in clinical situation and in cancer research. The major factor limiting the ability of M-FISH to resolve the chromosomal origin of the DNA in abnormal chromosomes is pixel classification accuracy. The goal of this project to develop improved software techniques for M-FISH to improve significantly the accuracy of pixel classification in M-FISH systems, but maximizing the impact of this important new technology on the practice of cytogenetics. The instruments that are commercially available now implement only rudimentary pixel classification algorithms for identifying the homologue origin of DNA. In this project, we will apply state-of-the-art pattern recognition techniques to M-FISH to improve pixel classification accuracy far beyond what is current offered by commercial systems. The improved M-FISH system that will result will automatically find and flag both subtle and complex structural abnormalities (insertions and translocations of genetic material) assisting both cancer research and genetic diagnosis. Once we have established feasibility in Phase I, we will use Phase II to develop the improvements fully and test the system in routine clinical use on prenatal, postnatal and cancer specimens from amniocentesis, peripheral blood, and bone marrow. The enhancements will be integrated into PSI's M- FISH instrument, currently part of the PowerGene line of cytogenetics automation products. The resulting commercial instrument will be superior to currently available systems for elucidating structural rearrangements within chromosomes. PROPOSED COMMERCIAL APPLICATION: As soon as the new techniques are developed and qualified for routine application, they will be incorporated into PSI's PowerGene product line of cytogenetics automation equipment, both in new systems sold and as an upgrade to existing systems already in use in cytogenetics labs. Newly developed chromosome painting probes will be added to PSI's reagent product line, thus commercializing the technology quickly.