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Background  Biclustering algorithms belong to a distinct class of clustering algorithms that perform simultaneous clustering of both rows and columns of the gene expression matrix and can be a very useful analysis tool when some genes have multiple functions and experimental conditions are diverse. Cheng and Church have introduced a measure called mean squared residue score to evaluate the quality of a bicluster and has become one of the most popular measures to search for biclusters. In this paper, we review basic concepts of the metaheuristics  Greedy Randomized Adaptive Search Procedure (GRASP) -construction and local search phases and propose a new method which is a variant of  GRASP  called  Reactive Greedy Randomized Adaptive Search Procedure (Reactive GRASP)  to detect significant biclusters from large microarray datasets. The method has two major steps. First, high quality bicluster seeds are generated by means of k-means clustering. In the second step, these seeds are grown using the Reactive GRASP, in which the basic parameter that defines the restrictiveness of the candidate list is self-adjusted, depending on the quality of the solutions found previously.    Results  We performed statistical and biological validations of the biclusters obtained and evaluated the method against the results of basic GRASP and as well as with the classic work of Cheng and Church. The experimental results indicate that the Reactive GRASP approach outperforms the basic GRASP algorithm and Cheng and Church approach.    Conclusion  The Reactive GRASP approach for the detection of significant biclusters is robust and does not require calibration efforts.

Biclustering of gene expression data using reactive greedy randomized adaptive search procedure