Modeling human cancer-related regulatory modules by GA-RNN hybrid algorithms.
BACKGROUND
Modeling cancer-related regulatory modules from gene expression profiling of cancer tissues is expected to contribute to our understanding of cancer biology as well as developments of new diagnose and therapies. Several mathematical models have been used to explore the phenomena of transcriptional regulatory mechanisms in Saccharomyces cerevisiae. However, the contemplating on controlling of feed-forward and feedback loops in transcriptional regulatory mechanisms is not resolved adequately in Saccharomyces cerevisiae, nor is in human cancer cells.


RESULTS
In this study, we introduce a Genetic Algorithm-Recurrent Neural Network (GA-RNN) hybrid method for finding feed-forward regulated genes when given some transcription factors to construct cancer-related regulatory modules in human cancer microarray data. This hybrid approach focuses on the construction of various kinds of regulatory modules, that is, Recurrent Neural Network has the capability of controlling feed-forward and feedback loops in regulatory modules and Genetic Algorithms provide the ability of global searching of common regulated genes. This approach unravels new feed-forward connections in regulatory models by modified multi-layer RNN architectures. We also validate our approach by demonstrating that the connections in our cancer-related regulatory modules have been most identified and verified by previously-published biological documents.


CONCLUSIONS
The major contribution provided by this approach is regarding the chain influences upon a set of genes sequentially. In addition, this inverse modeling correctly identifies known oncogenes and their interaction genes in a purely data-driven way.
Chiang
Jung-Hsien
JH
Department of Computer Science and Information Engineering, National Cheng Kung University, Tanian, Taiwan. jchiang@mail.ncku.edu.tw
Chao
Shih-Yi
SY
D000465:Algorithms; D001665:Binding Sites; D003198:Computer Simulation; D004273:DNA, Neoplasm / Q000235:genetics*; D006801:Humans; D008957:Models, Genetic; D009363:Neoplasm Proteins / Q000235:genetics*; D009369:Neoplasms / Q000235:genetics*; D016571:Neural Networks, Computer; D011485:Protein Binding; D050436:Regulatory Elements, Transcriptional / Q000235:genetics*; D017422:Sequence Analysis, DNA / Q000379:methods; D014157:Transcription Factors / Q000235:genetics*; D015533:Transcriptional Activation / Q000235:genetics*
D004273:DNA, Neoplasm; D009363:Neoplasm Proteins; D014157:Transcription Factors