self-correcting maps of molecular pathways自我修正的分子途径的地图.pdfVIP

Self-Correcting Maps of Molecular Pathways Andrey Rzhetsky1,2,*., Tian Zheng3., Chani Weinreb1. 1 Department of Biomedical Informatics, Center for Computational Biology and Bioinformatics and Joint Centers for Systems Biology, Columbia University, New York, New York, United States of America, 2 Judith P. Sulzberger MD Columbia Genome Center and Department of Biology, Columbia University, New York, New York, United States of America, 3 Department of Statistics, Columbia University, New York, New York, United States of America Reliable and comprehensive maps of molecular pathways are indispensable for guiding complex biomedical experiments. Such maps are typically assembled from myriads of disparate research reports and are replete with inconsistencies due to variations in experimental conditions and/or errors. It is often an intractable task to manually verify internal consistency over a large collection of experimental statements. To automate large-scale reconciliation efforts, we propose a random-arcs-and-nodes model where both nodes (tissue-specific states of biological molecules) and arcs (interactions between them) are represented with random variables. We show how to obtain a non-contradictory model of a molecular network by computing the joint distribution for arc and node variables, and then apply our methodology to a realistic network, generating a set of experimentally testable hypotheses. This network, derived from an automated analysis of over 3,000 full-text research articles, includes genes that have been hypothetically linked to four neurological disorders: Alzheimer’s disease, autism, bipolar disorder, and schizophrenia. We estimated that approximately 10% of the published molecular interactions are logically incompatible. Our approach can be directly applied to an array of diverse problems including those encountered in molecular bio