Towards precise classification of cancers based on robust gene functional expression profiles.
BACKGROUND
Development of robust and efficient methods for analyzing and interpreting high dimension gene expression profiles continues to be a focus in computational biology. The accumulated experiment evidence supports the assumption that genes express and perform their functions in modular fashions in cells. Therefore, there is an open space for development of the timely and relevant computational algorithms that use robust functional expression profiles towards precise classification of complex human diseases at the modular level.


RESULTS
Inspired by the insight that genes act as a module to carry out a highly integrated cellular function, we thus define a low dimension functional expression profile for data reduction. After annotating each individual gene to functional categories defined in a proper gene function classification system such as Gene Ontology applied in this study, we identify those functional categories enriched with differentially expressed genes. For each functional category or functional module, we compute a summary measure (s) for the raw expression values of the annotated genes to capture the overall activity level of the module. In this way, we can treat the gene expressions within a functional module as an integrative data point to replace the multiple values of individual genes. We compare the classification performance of decision trees based on functional expression profiles with the conventional gene expression profiles using four publicly available datasets, which indicates that precise classification of tumour types and improved interpretation can be achieved with the reduced functional expression profiles.


CONCLUSIONS
This modular approach is demonstrated to be a powerful alternative approach to analyzing high dimension microarray data and is robust to high measurement noise and intrinsic biological variance inherent in microarray data. Furthermore, efficient integration with current biological knowledge has facilitated the interpretation of the underlying molecular mechanisms for complex human diseases at the modular level.
Guo
Zheng
Z
Department of Computer Science, Harbin Institute of Technology, Harbin 150001, China. guoz@ems.hrbmu.edu.cn
Zhang
Tianwen
T
Li
Xia
X
Wang
Qi
Q
Xu
Jianzhen
J
Yu
Hui
H
Zhu
Jing
J
Wang
Haiyun
H
Wang
Chenguang
C
Topol
Eric J
EJ
Wang
Qing
Q
Rao
Shaoqi
S
D000465:Algorithms; D016000:Cluster Analysis; D019295:Computational Biology / Q000379:methods*; D003627:Data Interpretation, Statistical; D003628:Database Management Systems; D030541:Databases, Genetic; D030561:Databases, Nucleic Acid; D003663:Decision Trees; D020869:Gene Expression Profiling; D005786:Gene Expression Regulation; D015972:Gene Expression Regulation, Neoplastic; D020022:Genetic Predisposition to Disease; D023281:Genomics; D006801:Humans; D016247:Information Storage and Retrieval; D008957:Models, Genetic; D015233:Models, Statistical; D009369:Neoplasms / Q000145:classification* / Q000235:genetics*; D020411:Oligonucleotide Array Sequence Analysis; D010363:Pattern Recognition, Automated; D012984:Software; D014584:User-Computer Interface