原创力文档single sample expression-anchored mechanisms predict survival in head and neck cancer单样本expression-anchored预测在头部和颈部癌症生存机制.pdfVIP
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single sample expression-anchored mechanisms predict survival in head and neck cancer单样本expression-anchored预测在头部和颈部癌症生存机制
Single Sample Expression-Anchored Mechanisms Predict
Survival in Head and Neck Cancer
Xinan Yang1,2, Kelly Regan1¤, Yong Huang1,2, Qingbei Zhang1,2, Jianrong Li1,2¤, Tanguy Y. Seiwert3,4,
Ezra E. W. Cohen3,4, H. Rosie Xing4,5,6, Yves A. Lussier1,2,4,5,6,7¤*
1 Center for Biomedical Informatics, The University of Chicago, Chicago, Illinois, United States of America, 2 Section of Genetic Medicine, The University of Chicago,
Chicago, Illinois, United States of America, 3 Section of Hematology/Oncology of the Department of Medicine, The University of Chicago, Chicago, Illinois, United States of
America, 4 Comprehensive Cancer Center, The University of Chicago, Chicago, Illinois, United States of America, 5 Departments of Pathology and of Cellular and Radiation
Oncology, The University of Chicago, Chicago, Illinois, United States of America, 6 Ludwig Center for Metastasis Research, The University of Chicago, Chicago, Illinois,
United States of America, 7 Computation Institute, Institute for Translational Medicine, and Institute for Genomics and Systems Biology, The University of Chicago,
Chicago, Illinois, United States of America
Abstract
Gene expression signatures that are predictive of therapeutic response or prognosis are increasingly useful in clinical care;
however, mechanistic (and intuitive) interpretation of expression arrays remains an unmet challenge. Additionally, there is
surprisingly little gene overlap among distinct clinically validated expression signatures. These ‘‘causality challenges’’ hinder
the adoption of signatures as compared to functionally well-characterized single gene biomarkers. To increase the utility of
multi-gene signatures in survival studies, we developed a novel approach to generate ‘‘personal mechanism signatures’’ of
molecular pathways and functions from gene expression arrays. FAIME, the Functional Analysis of Individual Micr
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