TY - JOUR

T1 - Biclustering via optimal re-ordering of data matrices in systems biology

T2 - Rigorous methods and comparative studies

AU - DiMaggio, Peter A.

AU - McAllister, Scott R.

AU - Floudas, Christodoulos A.

AU - Feng, Xiao Jiang

AU - Rabinowitz, Joshua D.

AU - Rabitz, Herschel A.

N1 - Funding Information:
The authors gratefully acknowledge funding from the US Environmental Protection Agency (GAD R 832721-010) and C.A.F. gratefully acknowledges financial support from the National Science Foundation. Although the research described in the article has been funded in part by the U.S. Environmental Protection Agency's STAR program through grant (R 832721-010), it has not been subjected to any EPA review and therefore does not necessarily reflect the views of the Agency, and no official endorsement should be inferred. Special thanks to Chad Myers for providing the curated set of biological processes and helpful discussions during the preparation of this manuscript.

PY - 2008/10/27

Y1 - 2008/10/27

N2 - Background: The analysis of large-scale data sets via clustering techniques is utilized in a number of applications. Biclustering in particular has emerged as an important problem in the analysis of gene expression data since genes may only jointly respond over a subset of conditions. Biclustering algorithms also have important applications in sample classification where, for instance, tissue samples can be classified as cancerous or normal. Many of the methods for biclustering, and clustering algorithms in general, utilize simplified models or heuristic strategies for identifying the "best" grouping of elements according to some metric and cluster definition and thus result in suboptimal clusters. Results: In this article, we present a rigorous approach to biclustering, OREO, which is based on the Optimal RE-Ordering of the rows and columns of a data matrix so as to globally minimize the dissimilarity metric. The physical permutations of the rows and columns of the data matrix can be modeled as either a network flow problem or a traveling salesman problem. Cluster boundaries in one dimension are used to partition and re-order the other dimensions of the corresponding submatrices to generate biclusters. The performance of OREO is tested on (a) metabolite concentration data, (b) an image reconstruction matrix, (c) synthetic data with implanted biclusters, and gene expression data for (d) colon cancer data, (e) breast cancer data, as well as (f) yeast segregant data to validate the ability of the proposed method and compare it to existing biclustering and clustering methods. Conclusion: We demonstrate that this rigorous global optimization method for biclustering produces clusters with more insightful groupings of similar entities, such as genes or metabolites sharing common functions, than other clustering and biclustering algorithms and can reconstruct underlying fundamental patterns in the data for several distinct sets of data matrices arising in important biological applications.

AB - Background: The analysis of large-scale data sets via clustering techniques is utilized in a number of applications. Biclustering in particular has emerged as an important problem in the analysis of gene expression data since genes may only jointly respond over a subset of conditions. Biclustering algorithms also have important applications in sample classification where, for instance, tissue samples can be classified as cancerous or normal. Many of the methods for biclustering, and clustering algorithms in general, utilize simplified models or heuristic strategies for identifying the "best" grouping of elements according to some metric and cluster definition and thus result in suboptimal clusters. Results: In this article, we present a rigorous approach to biclustering, OREO, which is based on the Optimal RE-Ordering of the rows and columns of a data matrix so as to globally minimize the dissimilarity metric. The physical permutations of the rows and columns of the data matrix can be modeled as either a network flow problem or a traveling salesman problem. Cluster boundaries in one dimension are used to partition and re-order the other dimensions of the corresponding submatrices to generate biclusters. The performance of OREO is tested on (a) metabolite concentration data, (b) an image reconstruction matrix, (c) synthetic data with implanted biclusters, and gene expression data for (d) colon cancer data, (e) breast cancer data, as well as (f) yeast segregant data to validate the ability of the proposed method and compare it to existing biclustering and clustering methods. Conclusion: We demonstrate that this rigorous global optimization method for biclustering produces clusters with more insightful groupings of similar entities, such as genes or metabolites sharing common functions, than other clustering and biclustering algorithms and can reconstruct underlying fundamental patterns in the data for several distinct sets of data matrices arising in important biological applications.

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U2 - 10.1186/1471-2105-9-458

DO - 10.1186/1471-2105-9-458

M3 - Article

C2 - 18954459

AN - SCOPUS:57949105676

SN - 1471-2105

VL - 9

JO - BMC bioinformatics

JF - BMC bioinformatics

M1 - 458

ER -