Improved Classifiers for Multiplex FISH

描述(由申请人提供)： 自动化核型分析是世界各地细胞遗传学实验室的重要程序。多重荧光原位杂交(M-FISH)是一个相对较新的发展，它使用多色染色体涂染探针和多光谱图像分析来识别微妙和复杂的染色体重排。它承诺使自动化核型分析更快、更准确、更容易解释，无论是在临床情况下还是在癌症研究中。限制M-FISH仪器分辨异常染色体中DNA的染色体起源的主要因素是像素分类精度。该项目的目标是开发改进的软件技术，以显著提高M-FISH系统中像素分类的准确性，从而最大限度地发挥这一重要新技术对细胞遗传学实践的影响。商业上可用的仪器现在只实现了相对初级的像素分类算法来识别染色体DNA的同源来源。在这个项目中，我们将最先进的模式识别技术应用到M-FISH中，以提高像素分类精度，远远超过目前商业系统所提供的精度。这项研究将产生的改进的M-FISH系统将以高精度自动发现和标记细微和复杂的结构异常(遗传物质的插入和易位)，从而帮助癌症研究和基因诊断。在第一阶段确定了几项算法创新的可行性后，我们计划在第二阶段全面开发这些改进，并在常规临床使用中测试该系统，用于从羊膜穿刺术、外周血和骨髓中提取的产前、出生后和癌症样本。这些改进将被整合到商业上可用的M-FISH仪器中。由此产生的第二代商业仪器将优于目前可用的系统，用于阐明染色体内的结构重排。某些技术也将被公布，以造福于其他使用M-FISH的人。

DESCRIPTION (provided by applicant): Automated karyotyping is an important procedure in cytogenetics labs worldwide. Multiplex fluorescence in situ hybridization (M-FISH) is a relatively 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 situations and in cancer research. The major factor limiting the ability of M-FISH instruments to resolve the chromosomal origin of the DNA in abnormal chromosomes is pixel classification accuracy. The goal of this project is to develop improved software techniques to improve significantly the accuracy of pixel classification in M-FISH systems, thereby maximizing the impact of this important new technology on the practice of cytogenetics. The instruments that are commercially available now implement only relatively rudimentary pixel classification algorithms for identifying the homologue origin of chromosomal DNA. In this project, we apply state-of-the-art pattern recognition techniques to M-FISH to improve pixel classification accuracy far beyond what is currently offered by commercial systems. The improved M-FISH system that will result from this research will automatically find and flag both subtle and complex structural abnormalities (insertions and translocations of genetic material) with high accuracy, thereby assisting both cancer research and genetic diagnosis. Having established feasibility of several algorithmic innovations in Phase I, we plan, in Phase II, to develop these 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 commercially available M-FISH instruments. The resulting second generation commercial instruments will be superior to currently available systems for elucidating structural rearrangements within chromosomes. Certain of the techniques will be published as well, to the benefit of others using M-FISH.