average rank-based score to measure deregulation of molecular pathway gene setsrank-based平均得分来衡量放松管制的分子通路基因集.pdfVIP

Average Rank-Based Score to Measure Deregulation of Molecular Pathway Gene Sets 1. 2,3 . 1 Huan Yang , Chao Cheng * , Wei Zhang * 1 Department of Reproductive Endocrinology, Obstetrics and Gynecology Hospital, Fudan University, Shanghai, China, 2 Program in Computational Biology and Bioinformatics, Yale University, New Haven, Connecticut, United States of America, 3 Department of Molecular Biophysics and Biochemistry, Yale University, New Haven, Connecticut, United States of America Abstract Background: Deregulation of biological pathways has been shown to be involved in the turmorigenesis of a variety of cancers. The co-regulation of pathways in tumor and normal tissues has not been studied in a systematic manner. Results: In this study we propose a novel statistic named AR-score (average rank based score) to measure pathway activities based on microarray gene expression profiles. We calculate and compare the AR-scores of pathways in microarray datasets containing expression profiles for a wide range of cancer types as well as the corresponding normal tissues. We find that many pathways undergo significant activity changes in tumors with respect to normal tissues. AR-scores for a small subset of pathways are capable of distinguishing tumor from normal tissues or classifying tumor subtypes. In normal tissues many pathways are highly correlated in their activities, whereas their correlations reduce significantly in tumors and cancer cell lines. The co-expression of genes in the same pathways was also significantly perturbed in tumors. Conclusions: The co-regulation of genes in the same pathways and co-regulation of different pathways are significantly perturbed in tumors versus normal tissues. Our method provides a useful tool for better understanding the mechanistic change