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Title: A linear programming approach for estimating the structure of a sparse linear genetic network from transcript profiling data

Journal Article · · Algorithms for Molecular Biology
 [1];  [2];  [3];  [4]
  1. Indian Inst. of Science, Bangalore (India). Dept. of Computer Science and Automation
  2. Indian Inst. of Science, Bangalore (India). Dept. of Computer Science and Automation; Indian Inst. of Science, Bangalore (India). Bioinformatics Centre
  3. Indian Inst. of Science, Bangalore (India). Bioinformatics Centre
  4. Lawrence Berkeley National Lab. (LBNL), Berkeley, CA (United States). Life Sciences Division
+ Show Author Affiliations

Background: A genetic network can be represented as a directed graph in which a node corresponds to a gene and a directed edge specifies the direction of influence of one gene on another. The reconstruction of such networks from transcript profiling data remains an important yet challenging endeavor. A transcript profile specifies the abundances of many genes in a biological sample of interest. Prevailing strategies for learning the structure of a genetic network from highdimensional transcript profiling data assume sparsity and linearity. Many methods consider relatively small directed graphs, inferring graphs with up to a few hundred nodes. This work examines large undirected graphs representations of genetic networks, graphs with many thousands of nodes where an undirected edge between two nodes does not indicate the direction of influence, and the problem of estimating the structure of such a sparse linear genetic network (SLGN) from transcript profiling data. Results: The structure learning task is cast as a sparse linear regression problem which is then posed as a LASSO (l 1-constrained fitting) problem and solved finally by formulating a Linear Program (LP). A bound on the Generalization Error of this approach is given in terms of the LeaveOne-Out Error. The accuracy and utility of LP-SLGNs is assessed quantitatively and qualitatively using simulated and real data. The Dialogue for Reverse Engineering Assessments and Methods (DREAM) initiative provides gold standard data sets and evaluation metrics that enable and facilitate the comparison of algorithms for deducing the structure of networks. The structures of LP-SLGNs estimated from the INSILICO1, INSILICO2 and INSILICO3 simulated DREAM2 data sets are comparable to those proposed by the first and/or second ranked teams in the DREAM2 competition. The structures of LP-SLGNs estimated from two published Saccharomyces cerevisae cell cycle transcript profiling data sets capture known regulatory associations. In each S. cerevisiae LP-SLGN, the number of nodes with a particular degree follows an approximate power law suggesting that its degree distributions is similar to that observed in real-world networks. Inspection of these LP-SLGNs suggests biological hypotheses amenable to experimental verification.

Sponsoring Organization:
USDOE Office of Science (SC), Biological and Environmental Research (BER). Biological Systems Science Division
Grant/Contract Number:
AC02-05CH11231
OSTI ID:
1626634
Journal Information:
Algorithms for Molecular Biology, Vol. 4, Issue 1; ISSN 1748-7188
Publisher:
BioMed CentralCopyright Statement
Country of Publication:
United States
Language:
English

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