Jimin Song will present her preFPO on Thursday April 21 at 10AM in Carl Icahn Lab 280 (note room!). The members of her committee are: Mona Singh, advisor; Olga Troyanskaya and Tom Funkhouser, readers; Bernard Chazelle and Andrea LaPaugh, nonreaders. Everyone is invited to attend her talk. Her abstract follows below. ------------------------------------------- Protein functioning and the role of cellular network topology Virtually all biological processes are accomplished via numerous specific interactions amongst various types of molecules. In the past decade, experimental and computational technologies have determined large numbers of interactions of various types, including those corresponding to direct physical binding, to regulatory relationships, and to more abstract linkages such as genetic interactions which indicate that two proteins participate in related biological processes. Analysis of the resulting interaction networks are a promising approach for expanding our understanding of cellular functioning, pathways and organization. In this work, I use high-throughput protein physical interactions to uncover hints about the overall functional organization of the cell, and to understand the role of network topology in this functioning. In the first part of my thesis, I study the problem of uncovering, from large-scale protein physical interaction data, protein complexes and "functional modules", so-called groups of proteins that work together to perform some larger biological process. I develop a framework to assess how well network clustering approaches perform in uncovering protein complexes and biological processes, and in predicting protein functions. From an application of this framework, I find that topological characteristics of networks are a significant factor in the accuracy trade-offs between local and global (i.e. clustering) approaches for uncovering cellular functioning. In the second part of my thesis, I analyze protein physical interaction networks in order to better characterize a protein's essentiality (i.e., the property of whether a protein is necessary for a cell to survive) and to understand the interplay between different protein complexes and biological processes. First, in agreement with previous studies, I find that proteins that are central in cellular networks tend to be essential more frequently. Second, I find essential proteins within complexes and processes are topologically more central within these subnetworks. Third, I infer significant cross-talk relationships between complexes and processes. This "module network," comprised of complexes or processes as nodes and cross-talk between them as edges, shows how complexes and processes are organized in a cell. Finally, I uncover that essential complexes and processes are topologically more central in the module network.