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A scenario-based approach to modeling development: a prototype model of C. elegans vulval fate specification
Authors:Kam Na'aman  Kugler Hillel  Marelly Rami  Appleby Lara  Fisher Jasmin  Pnueli Amir  Harel David  Stern Michael J  Hubbard E Jane Albert
Affiliation:a The Weizmann Institute of Science, Department of Computer Science and Applied Mathematics, Rehovot 76100, Israel
b New York University, Department of Biology, 100 Washington Square East, 1009 Silver Center, New York, NY 10003, USA
c New York University, Courant Institute of Mathematical Sciences, Computer Science Department, Warren Weaver Hall, Room 405, 251 Mercer Street, New York, NY 10012, USA
d Microsoft Research Cambridge, Roger Needham Building, 7 J J Thomson Avenue, Cambridge CB3 0FB, UK
e Yale University School of Medicine, Department of Genetics, SHM I-354, P.O. Box 208005, New Haven, CT 06520-8005, USA
f New York University School of Medicine, Department of Pathology, Developmental Genetics Program, Skirball Institute of Biomolecular Medicine, The Helen L. and Martin S. Kimmel Center for Stem Cell Biology, 540 First Avenue, New York, NY 10016, USA
Abstract:Studies of developmental biology are often facilitated by diagram “models” that summarize the current understanding of underlying mechanisms. The increasing complexity of our understanding of development necessitates computational models that can extend these representations to include their dynamic behavior. Here we present a prototype model of Caenorhabditis elegans vulval precursor cell fate specification that represents many processes crucial for this developmental event but that are hard to integrate using other modeling methodologies. We demonstrate the integrative capabilities of our methodology by comprehensively incorporating the contents of three seminal papers, showing that this methodology can lead to comprehensive models of developmental biology. The prototype computational model was built and is run using a language (Live Sequence Charts) and tool (the Play-Engine) that facilitate the same conceptual processes biologists use to construct and probe diagram-type models. We demonstrate that this modeling approach permits rigorous tests of mutual consistency between experimental data and mechanistic hypotheses and can identify specific conflicting results, providing a useful approach to probe developmental systems.
Keywords:Vulval fate specification   VPC   Modeling   Scenario-based   Live Sequence Charts   C. elegans
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