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Reveal, A General Reverse Engineering Algorithm for Inference of Genetic Network ArchitecturesGiven the immanent gene expression mapping covering whole genomes during development, health and disease, we seek computational methods to maximize functional inference from such large data sets. Is it possible, in principle, to completely infer a complex regulatory network architecture from input/output patterns of its variables? We investigated this possibility using binary models of genetic networks. Trajectories, or state transition tables of Boolean nets, resemble time series of gene expression. By systematically analyzing the mutual information between input states and output states, one is able to infer the sets of input elements controlling each element or gene in the network. This process is unequivocal and exact for complete state transition tables. We implemented this REVerse Engineering ALgorithm (REVEAL) in a C program, and found the problem to be tractable within the conditions tested so far. For n = 50 (elements) and k = 3 (inputs per element), the analysis of incomplete state transition tables (100 state transition pairs out of a possible 10(exp 15)) reliably produced the original rule and wiring sets. While this study is limited to synchronous Boolean networks, the algorithm is generalizable to include multi-state models, essentially allowing direct application to realistic biological data sets. The ability to adequately solve the inverse problem may enable in-depth analysis of complex dynamic systems in biology and other fields.
Document ID
20010002317
Acquisition Source
Ames Research Center
Document Type
Reprint (Version printed in journal)
Authors
Liang, Shoudan
(Search for Extraterrestrial Intelligence Inst. Moffett Field, CA United States)
Fuhrman, Stefanie
(National Inst. of Health Bethesda, MD United States)
Somogyi, Roland
(National Inst. of Health Bethesda, MD United States)
Date Acquired
September 7, 2013
Publication Date
January 1, 1998
Publication Information
Volume: 3
Subject Category
Life Sciences (General)
Meeting Information
Meeting: Biocomputing
Country: United States
Start Date: January 1, 1998
Funding Number(s)
CONTRACT_GRANT: NCC2-974
Distribution Limits
Public
Copyright
Work of the US Gov. Public Use Permitted.
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