carolyn-pl-ssb-fm

carolyn-pl-ssb-fm - Using Formal Methods Tools to Model...

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Symbolic Systems Biology --- Using Formal Methods Tools to Model Biological Processes Carolyn Talcott SRI International SSFT May 2011 http://pl.csl.sri.com
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PLan Symbolic systems biology Pathway Logic Modeling Analyzing Case studies Choosing a formalism Future challenges
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Biological Systems Biological processes are complex signaling, regulation, defense, . ... Huge dynamics timescales: microseconds to years Spatial scales over 12 orders of magnitude single protein to cell to organ to organism . .. Oceans of experimental biological data generated Important intuitions captured in mental models that biologists build of biological processes How to build in silico models from all this?
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SyMbolic Systems Biology Symbolic -- represented in a logical framework Systems -- how things interact and work together, integration of multiple parts, viewpoints and levels of abstraction Goals: Develop formal models that are as close as possible to domain expert’s mental models Compute with, analyze and reason about complex networks New insights into / understanding of biological mechanisms
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Executable Formal Models Describe system states and rules for change in a formal system From an initial state, derive a transition graph nodes -- reachable states edges -- rules connecting states Path in transition graph ~ computation/derivation Many kinds of analysis available
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Pathway LogiC (PL) Representation of Signaling http://pl.csl.sri.com/
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Signaling PATHWAYS Signaling pathways involve the modification and/or assembly of proteins and other molecules within cellular compartments into complexes that coordinate and regulate the flow of information. Signaling pathways are distributed in networks having stimulatory (positive) and inhibitory (negative) feedback loops, and other concurrent interactions to ensure that signals are propagated and interpreted appropriately in a particular cell or tissue. Signaling networks are robust and adaptive, in part because of combinatorial complex formation (several building blocks for forming the same type of complex), redundant pathways, and feedback loops.
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Egf (EGF) binds to the Egf receptor (EgfR) and stimulates its protein tyrosine kinase activity to cause autophosphorylation, thus activating EgfR. The adaptor protein Grb2 (GRB2) and the guanine nucleotide exchange factor Sos1 (SOS) are recruited to the membrane, binding to EgfR. The EgfR complex activates a Ras family GTPase Activated Ras activates Raf1, a member of the RAF serine/threonine protein kinase family. Raf1 activates the protein kinase Mek (MEK), which then activates Erk (MAPK) ... from Wikipedia Egf stimulation of the Mitogen Activated Protein Kinase (MAPK) pathway. Egf EgfR Grb2 Sos1 Ras Raf1 Mek Erk
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Rewriting Logic Rewriting Logic is a logical formalism that is based on two simple ideas states of a system are represented as elements of an algebraic data type the behavior of a system is given by local transitions between states described by rewrite rules
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This note was uploaded on 02/07/2012 for the course CS 4322 taught by Professor Martinrinard during the Spring '11 term at MIT.

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carolyn-pl-ssb-fm - Using Formal Methods Tools to Model...

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