We develop and apply novel computational approaches in systems and network biology. Our main goals are to identify the cellular pathways that underlie human diseases and to decipher the remarkable robustness of cellular systems.
Construction & analysis of molecular interactomes: Interactomes are networks that represent the molecular interactions within an organism, often focusing on interactions among proteins, genes and microRNAs. Since all cellular processes rely on molecular interactions, these networks provide a scaffold for identifying the functions of proteins and the organization of cellular pathways in health & disease. We have been studying the properties of these interactomes across different human tissues (Barshir et al, 2013), uncovered their building blocks of integrative regulatory systems (Yeger-Lotem et al, 2004), and harnessed them to reveal the signaling and regulatory pathways perturbed during diseases (Yeger-Lotem et al, Nat Genet 2009, Lan et al, ISMB 2013).
Pathway analysis: Identification of molecules and cellular pathways perturbed in diseases can open new avenues in disease understanding and therapy. Current experimental approaches offer an unprecedented large-scale view into the genetic, transcriptional and proteomic changes that distinguish disease states. However, these views are hard to interpret. We develop novel integrative approaches that harness these large-scale measurements in order to obtain a concise and meaningful view of the underlying disease processes. Our ResponseNet frameowrk is capable of identifying perturbed regulatory and signaling pathways (Yeger-Lotem et al, Nat Genet 2009), and is available here (Lan et al, NAR 2011, Basha et al, NAR 2013). We recently developed ContextNet capable of identifying context-sensitive pawthays (Lan et al, ISMB 2013).
Cellular circuitry: Cellular systems are amazingly robust to genetic and environmental changes. Cellular regulatory systems are key in understanding this robustness as they propagate signals and invoke cellular responses. We have been studying the circuitry of cellular regulatory systems. We identified molecular feedback loops (Yeger-Lotem et al, NAR 2003) and network motifs (Yeger-Lotem et al, PNAS 2004) in integrated networks involving transcription regulation and protein interactions. We revealed previously hidden relationship between transcription regulation and gene neighborhood (Hershberg et al, TIG 2005).
Open web-tools: All the tools we develop are open for usage by the scientific community, see our tools page.