Abstract

With the development of next-generation DNA sequencing technologies, large-scale cancer genomics projects can be implemented to help researchers to identify driver genes, driver mutations, and driver pathways, which promote cancer proliferation in large numbers of cancer patients. Hence, one of the remaining challenges is to distinguish functional mutations vital for cancer development, and filter out the unfunctional and random “passenger mutations.” In this study, we introduce a modified method to solve the so-called maximum weight submatrix problem which is used to identify mutated driver pathways in cancer. The problem is based on two combinatorial properties, that is, coverage and exclusivity. Particularly, we enhance an integrative model which combines gene mutation and expression data. The experimental results on simulated data show that, compared with the other methods, our method is more efficient. Finally, we apply the proposed method on two real biological datasets. The results show that our proposed method is also applicable in real practice.

Highlights

  • Cancer is a fatal disease which is extremely complex

  • In order to solve this problem, in this paper, based on GA method introduced by Zhao et al [21], we propose the simulated annealing hybrid genetic algorithm (SAGA) method for mutated driver pathway detecting

  • We first tested the ability of the SAGA to detect the set M of maximum weight submatrix and compared the result with the Markov chain Monte Carlo (MCMC) and GA methods

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Summary

Introduction

Researchers have found that cancer should be arisen by singlenucleotide mutations, larger copy-number aberrations, or structural aberrations [1]. The dreadful feature of cancer cells is infinite proliferation. These abnormal cells can spread to other tissues through blood circulation or lymphatic system [2]. With the development of next-generation DNA sequencing technologies, large-scale cancer genomics projects have been implemented to help researchers to identify driver genes, driver mutations, and driver pathways which promote cancer proliferation in large numbers of cancer patients [4,5,6]. It is necessary to find efficient methods for identifying mutated driver pathways in cancer cells, which can be further used to aid in designing effective drugs to treat cancer [7, 8]

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