Biomarker identification by knowledge-driven multilevel ICA and motif analysis

被引:9
作者
Chen, Li [1 ]
Xuan, Jianhua [1 ]
Wang, Chen [1 ]
Wang, Yue [1 ]
Shih, Ie-Ming [2 ]
Wang, Tian-Li [2 ]
Zhang, Zhen [2 ]
Clarke, Robert [3 ]
Hoffman, Eric P. [4 ]
机构
[1] Virginia Polytech Inst & State Univ, Dept Elect & Comp Engn, Arlington, VA 22203 USA
[2] Johns Hopkins Univ, Sch Med, Dept Pathol Gynecol & Oncol, Baltimore, MD 21231 USA
[3] Georgetown Univ, Sch Med, Dept Oncol & Physiol & Biophys, Washington, DC 20057 USA
[4] Childrens Natl Med Ctr, Med Genet Res Ctr, Washington, DC 20010 USA
关键词
biomarker identification; multi-level ICA; motif analysis; gene clustering; gene regulatory networks; microarray data analysis; ICA; independent component analysis; EXPRESSION PROFILES; REGULATORY MODULES; OVARIAN-CANCER; GENE; NETWORKS;
D O I
10.1504/IJDMB.2009.029201
中图分类号
Q [生物科学];
学科分类号
07 ; 0710 ; 09 ;
摘要
Traditional statistical methods often fail to identify biologically meaningful biomarkers from expression data alone. In this paper, we develop a novel strategy, namely knowledge-driven multi-level Independent Component Analysis (ICA), to infer regulatory signals and identify biomarkers based on clustering results and partial prior knowledge. A statistical test is designed to evaluate significance of transcription factor enrichment for extracted gene set based on motif information. The experimental results on an Rsf-1 (HBXAP) induced microarray data set show that our method can successfully extract biologically meaningful biomarkers related to ovarian cancer compared to other gene selection methods with or without prior knowledge.
引用
收藏
页码:365 / 381
页数:17
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