Bi-(N-) cluster editing and its biomedical applications

Abstract

he extremely fast advances in wet-lab techniques lead to an exponential growth of heterogeneous and unstructured biological data, posing a great challenge to data integration in nowadays system biology. The traditional clustering approach, although widely used to divide the data into groups sharing common features, is less powerful in the analysis of heterogeneous data from n different sources (n _ 2). The co-clustering approach has been widely used for combined analyses of multiple networks to address the challenge of heterogeneity. In this thesis, novel methods for the co-clustering of large scale heterogeneous data sets are presented in the software package n-CluE: one exact algorithm and two heuristic algorithms based on the model of bi-/n-cluster editing by modeling the input as n-partite graphs and solving the clustering problem with various strategies. In the first part of the thesis, the complexity and the fixed-parameter tractability of the extended bicluster editing model with relaxed constraints are investigated, namely the ?-bicluster editing model and its NP-hardness is proven. Based on the results of this analysis, three strategies within the n-CluE software package are then established and discussed, together with the evaluations on performances and the systematic comparisons against other algorithms of the same type in solving bi-/n-cluster editing problem. To demonstrate the practical impact, three real-world analyses using n-CluE are performed, including (a) prediction of novel genotype-phenotype associations by clustering the data from Genome-Wide Association Studies; (b) comparison between n-CluE and eight other biclustering tools on GEO Omnibus microarray data sets; (c) drug repositioning predictions by co-clustering on drug, gene and disease networks. The outstanding performance of n-CluE in the real-world applications shows its strength and flexibility in integrating heterogeneous data and extracting biological relevant information in bioinformatic analyses