Gene expression module-based chemical function similarity search.
Investigation of biological processes using selective chemical interventions is generally applied in biomedical research and drug discovery. Many studies of this kind make use of gene expression experiments to explore cellular responses to chemical interventions. Recently, some research groups constructed libraries of chemical related expression profiles, and introduced similarity comparison into chemical induced transcriptome analysis. Resembling sequence similarity alignment, expression pattern comparison among chemical intervention related expression profiles provides a new way for chemical function prediction and chemical-gene relation investigation. However, existing methods place more emphasis on comparing profile patterns globally, which ignore noises and marginal effects. At the same time, though the whole information of expression profiles has been used, it is difficult to uncover the underlying mechanisms that lead to the functional similarity between two molecules. Here a new approach is presented to perform biological effects similarity comparison within small biologically meaningful gene categories. Regarding gene categories as units, a reduced similarity matrix is generated for measuring the biological distances between query and profiles in library and pointing out in which modules do chemical pairs resemble. Through the modularization of expression patterns, this method reduces experimental noises and marginal effects and directly correlates chemical molecules with gene function modules.
Li
Yun
Y
Key Lab of Systems Biology, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, 320 Yueyang Road, Shanghai 200031, Shanghai, PR China.
Hao
Pei
P
Zheng
Siyuan
S
Tu
Kang
K
Fan
Haiwei
H
Zhu
Ruixin
R
Ding
Guohui
G
Dong
Changzheng
C
Wang
Chuan
C
Li
Xuan
X
Thiesen
H-J
HJ
Chen
Y Eugene
YE
Jiang
Hualiang
H
Liu
Lei
L
Li
Yixue
Y
D000970:Antineoplastic Agents / Q000494:pharmacology; D001943:Breast Neoplasms / Q000235:genetics; D015687:Cell Hypoxia; D045744:Cell Line, Tumor; D015342:DNA Probes; D005260:Female; D015870:Gene Expression / Q000187:drug effects*; D020869:Gene Expression Profiling / Q000379:methods*; D053263:Gene Regulatory Networks; D006801:Humans; D020411:Oligonucleotide Array Sequence Analysis
D000970:Antineoplastic Agents; D015342:DNA Probes