title: Epidermal Growth Factor Signaling towards Proliferation: Modeling and Logic Inference Using Forward and Backward Search.
abstract: In biological systems, pathways define complex interaction networks where multiple molecular elements are involved in a series of controlled reactions producing responses to specific biomolecular signals. These biosystems are dynamic and there is a need for mathematical and computational methods able to analyze the symbolic elements and the interactions between them and produce adequate readouts of such systems. In this work, we use rewriting logic to analyze the cellular signaling of epidermal growth factor (EGF) and its cell surface receptor (EGFR) in order to induce cellular proliferation. Signaling is initiated by binding the ligand protein EGF to the membrane-bound receptor EGFR so as to trigger a reactions path which have several linked elements through the cell from the membrane till the nucleus. We present two different types of search for analyzing the EGF/proliferation system with the help of Pathway Logic tool, which provides a knowledge-based development environment to carry out the modeling of the signaling. The first one is a standard (forward) search. The second one is a novel approach based onnarrowing, which allows us to trace backwards the causes of a given final state. The analysis allows the identification of critical elements that have to be activated to provoke proliferation.
authors.affiliation: Universidad Complutense de Madrid, Madrid, Spain.
authors.forename: Adrián
authors.initials: A
authors.lastname: Riesco
authors.affiliation: Bio and Health Informatics Lab, Seoul National University, Seoul, Republic of Korea.
authors.forename: Beatriz
authors.initials: B
authors.lastname: Santos-Buitrago
authors.affiliation: Cancer Research Center (CSIC/USAL) and IBSAL, Salamanca, Spain.
authors.forename: Javier
authors.initials: J
authors.lastname: De Las Rivas
authors.affiliation: Biosciences Division, SRI International, Menlo Park, CA, USA.
authors.forename: Merrill
authors.initials: M
authors.lastname: Knapp
authors.affiliation: University of Salamanca, Salamanca, Spain.
authors.forename: Gustavo
authors.identifier: 0000-0001-6609-5493
authors.initials: G
authors.lastname: Santos-García
authors.affiliation: Computer Science Laboratory, SRI International, Menlo Park, CA, USA.
authors.forename: Carolyn
authors.initials: C
authors.lastname: Talcott
mesh_terms: D049109:Cell Proliferation; D004815:Epidermal Growth Factor / Q000378:metabolism*; D066246:ErbB Receptors / Q000378:metabolism; D006801:Humans; D008128:Logic; D008954:Models, Biological; D015398:Signal Transduction
chemical_list: D004815:Epidermal Growth Factor; D066246:ErbB Receptors