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A Method to Identify and Analyze Biological Programs through Automated Reasoning.

Published version
Peer-reviewed

Repository DOI


Type

Article

Change log

Authors

Yordanov, Boyan 
Dunn, Sara-Jane 
Kugler, Hillel 
Martello, Graziano 

Abstract

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.

Description

Keywords

0801 Artificial Intelligence and Image Processing

Journal Title

NPJ Syst Biol Appl

Conference Name

Journal ISSN

2056-7189
2056-7189

Volume Title

2

Publisher

Nature
Sponsorship
Medical Research Council (MC_PC_12009)
MRC (G1100526)
G.M. holds a career development award from the Armenise Harvard foundation, and a Telethon-DTI career award. A.G.S. is a Medical Research Council Professor.