A scenario-based approach to modeling development: a prototype model of C. elegans vulval fate specification.
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.
Kam
Na'aman
N
The Weizmann Institute of Science, Department of Computer Science and Applied Mathematics, Rehovot 76100, Israel.
Kugler
Hillel
H
Marelly
Rami
R
Appleby
Lara
L
Fisher
Jasmin
J
Pnueli
Amir
A
Harel
David
D
Stern
Michael J
MJ
Hubbard
E Jane Albert
EJ
D000818:Animals; D017173:Caenorhabditis elegans / Q000235:genetics / Q000254:growth & development* / Q000502:physiology; D019295:Computational Biology / Q000379:methods; D003198:Computer Simulation; D005260:Female; D018507:Gene Expression Regulation, Developmental; D008954:Models, Biological; D014844:Vulva / Q000378:metabolism*