simultaneous clustering of multiple gene expression and physical interaction datasets同时集群的多个基因表达和物理交互数据集.pdfVIP

Simultaneous Clustering of Multiple Gene Expression and Physical Interaction Datasets 1 ¤a 2 1¤b 1 ¤c Manikandan Narayanan * , Adrian Vetta , Eric E. Schadt , Jun Zhu * 1 Department of Genetics, Rosetta Inpharmatics (Merck), Seattle, Washington, United States of America, 2 Department of Mathematics and Statistics, and School of Computer Science, McGill University, Montreal, Quebec, Canada Abstract Many genome-wide datasets are routinely generated to study different aspects of biological systems, but integrating them to obtain a coherent view of the underlying biology remains a challenge. We propose simultaneous clustering of multiple networks as a framework to integrate large-scale datasets on the interactions among and activities of cellular components. Specifically, we develop an algorithm JointCluster that finds sets of genes that cluster well in multiple networks of interest, such as coexpression networks summarizing correlations among the expression profiles of genes and physical networks describing protein-protein and protein-DNA interactions among genes or gene-products. Our algorithm provides an efficient solution to a well-defined problem of jointly clustering networks, using techniques that permit certain theoretical guarantees on the quality of the detected clustering relative to the optimal clustering. These guarantees coupled with an effective scaling heuristic and the flexibility to handle multiple heterogeneous networks make our method JointCluster an advance over earlier approaches. Simulation results showed JointCluster to be more robust than alternate methods in recovering clusters implanted in networks with high false positive rates. In sy