A Method to Identify and Analyze Biological Programs through Automated Reasoning.
Predictive biology is elusive because rigorous, data-constrained, mechanistic models of complex biological systems are difficult to derive and validate. Current approaches tend to construct and examine static interaction network models, which are descriptively rich but often lack explanatory and predictive power, or dynamic models that can be simulated to reproduce known behavior. However, in such approaches implicit assumptions are introduced as typically only one mechanism is considered, and exhaustively investigating all scenarios is impractical using simulation. To address these limitations, we present a methodology based on automated formal reasoning, which permits the synthesis and analysis of the complete set of logical models consistent with experimental observations. We test hypotheses against all candidate models, and remove the need for simulation by characterizing and simultaneously analyzing all mechanistic explanations of observed behavior. Our methodology transforms knowledge of complex biological processes from sets of possible interactions and experimental observations to precise, predictive biological programs governing cell function.
Microsoft Research, 21 Station Road, Cambridge, CB1 2FB, UK.
Boyan
B
Yordanov
Microsoft Research, 21 Station Road, Cambridge, CB1 2FB, UK.
Sara-Jane
SJ
Dunn
Microsoft Research, 21 Station Road, Cambridge, CB1 2FB, UK.|Faculty of Engineering, Bar-Ilan University, Ramat Gan, 5290002, Israel.
Hillel
H
Kugler
Wellcome Trust Medical Research Council Cambridge Stem Cell Institute, University of Cambridge CB2 1QR, UK.|Department of Biochemistry, University of Cambridge, Cambridge, UK.
Austin
A
Smith
Dept. of Molecular Medicine, Complesso Vallisneri - 3 Piano Nord, University of Padua, Viale G. Colombo 3, 35131 Padua, Italy.
Graziano
G
Martello
Microsoft Research, 21 Station Road, Cambridge, CB1 2FB, UK.|Faculty of Engineering Science, University College London, Torrington Place, London WC1E 7JE, UK.
Stephen
S
Emmott
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