title: Deciphering histone code of transcriptional regulation in malaria parasites by large-scale data mining.
abstract: Histone modifications play a major role in the regulation of gene expression. Accumulated evidence has shown that histone modifications mediate biological processes such as transcription cooperatively. This has led to the hypothesis of 'histone code' which suggests that combinations of different histone modifications correspond to unique chromatin states and have distinct functions. In this paper, we propose a framework based on association rule mining to discover the potential regulatory relations between histone modifications and gene expression in Plasmodium falciparum. Our approach can output rules with statistical significance. Some of the discovered rules are supported by literature of experimental results. Moreover, we have also discovered de novo rules which can guide further research in epigenetic regulation of transcription. Based on our association rules we build a model to predict gene expression, which outperforms a published Bayesian network model for gene expression prediction by histone modifications. The results of our study reveal mechanisms for histone modifications to regulate transcription in large-scale. Among our findings, the cooperation among histone modifications provides new evidence for the hypothesis of histone code. Furthermore, the rules output by our method can be used to predict the change of gene expression.
authors.affiliation: School of Computer Engineering, Nanyang Technological University, 50 Nanyang Avenue, Singapore 639798, Singapore. Electronic address: hchen009@e.ntu.edu.sg.
authors.forename: Haifen
authors.initials: H
authors.lastname: Chen
authors.affiliation: Department of Computer Science and Engineering, University of California Riverside, 900 University Avenue, Riverside, CA 92521, USA. Electronic address: stelo@cs.ucr.edu.
authors.forename: Stefano
authors.initials: S
authors.lastname: Lonardi
authors.affiliation: School of Computer Engineering, Nanyang Technological University, 50 Nanyang Avenue, Singapore 639798, Singapore; Genome Institute of Singapore, A*STAR (Agency for Science, Technology, and Research), Biopolis, Singapore 138672, Singapore. Electronic address: zhengjie@ntu.edu.sg.
authors.forename: Jie
authors.initials: J
authors.lastname: Zheng
mesh_terms: D019295:Computational Biology; D057225:Data Mining; D044127:Epigenesis, Genetic; D005786:Gene Expression Regulation; D017125:Genes, Protozoan; D042421:Histone Code; D008288:Malaria; D010963:Plasmodium falciparum / Q000235:genetics*; D014158:Transcription, Genetic
keywords: Association rule mining; Gene expression prediction; Histone code; Histone modification; Plasmodium falciparum