dominating biological networks控制生物网络.pdfVIP

Dominating Biological Networks ´ 1 ˇ ´2 3 ˇ ˇ 4 Tijana Milenkovic , Vesna Memisevic , Anthony Bonato , Natasa Przulj * 1 Department of Computer Science and Engineering, University of Notre Dame, Notre Dame, Indiana, United States of America, 2 Department of Computer Science, University of California Irvine, Irvine, California, United States of America, 3 Department of Mathematics, Ryerson University, Toronto, Ontario, Canada, 4 Department of Computing, Imperial College London, London, United Kingdom Abstract Proteins are essential macromolecules of life that carry out most cellular processes. Since proteins aggregate to perform function, and since protein-protein interaction (PPI) networks model these aggregations, one would expect to uncover new biology from PPI network topology. Hence, using PPI networks to predict protein function and role of protein pathways in disease has received attention. A debate remains open about whether network properties of ‘‘biologically central (BC)’’ genes (i.e., their protein products), such as those involved in aging, cancer, infectious diseases, or signaling and drug- targeted pathways, exhibit some topological centrality compared to the rest of the proteins in the human PPI network. To help resolve this debate, we design new network-based approaches and apply them to get new insight into biological function and disease. We hypothesize that BC genes have a topologically central (TC) role in the human PPI network. We propose two different concepts of topological centrality. We design a new centrality measure to capture c