Exploiting binary abstractions in deciphering gene interactions.
We consider computationally reconstructing gene regulatory networks on top of the binary abstraction of gene expression state information. Unlike previous Boolean network approaches, the proposed method does not handle noisy gene expression values directly. Instead, two-valued "hidden state" information is derived from gene expression profiles using a robust statistical technique, and a gene interaction network is inferred from this hidden state information. In particular, we exploit Espresso, a well-known 2-level Boolean logic optimizer in order to determine the core network structure. The resulting gene interaction networks can be viewed as dynamic Bayesian networks, which have key advantages over more conventional Bayesian networks in terms of biological phenomena that can be represented. The authors tested the proposed method with a time-course gene expression data set from microarray experiments on anti-cancer drugs doxorubicin and paclitaxel. A gene interaction network was produced by our method, and the identified genes were validated with a public annotation database. The experimental studies we conducted suggest that the proposed method inspired by engineering systems can be a very effective tool to decipher complex gene interactions in living systems.
Yoon
Sungroh
S
Comput. Syst. Lab., Stanford Univ., CA 94305, USA. sryoon@stanford.edu
Garg
Abhishek
A
Park
Hyun Seok
HS
Park
Woong Yang
WY
De Micheli
Giovanni
G
D000465:Algorithms; D001499:Bayes Theorem; D019295:Computational Biology / Q000379:methods*; D020869:Gene Expression Profiling; D005786:Gene Expression Regulation; D053263:Gene Regulatory Networks; D006801:Humans; D008957:Models, Genetic; D015233:Models, Statistical; D008962:Models, Theoretical; D020411:Oligonucleotide Array Sequence Analysis / Q000379:methods*; D012984:Software; D013997:Time Factors