An artificial neural network approach to the drug efficacy of interferon treatments.
BACKGROUND
Interferon taken alone or in combination with ribavirin can be used for the treatment of persons with chronic hepatitis C. It is highly desirable, both clinically and economically, to establish tools to distinguish responders from nonresponders and to predict possible outcomes of the treatments. In this work, our goal is to develop a prediction model resulting from the analysis of chronic hepatitis C patients' single nucleotide polymorphisms, viral genotype, viral load, age and gender, to predict the responsiveness of interferon combination treatment.


METHODS
We collected blood samples from 523 chronic hepatitis C patients that had received interferon and ribavirin combination therapy. Based on the current treatment strategy for chronic hepatitis C patients, we focused our search for candidate genes involved in pathways related to interferon signaling and immunomodulation. With artificial neural network algorithms, we then developed pattern recognition methodologies to achieve predictions among the patients. The artificial neural network model was trained by an algorithm with an adaptive momentum and learning rate.


RESULTS
There were seven single nucleotide polymorphisms selected from six candidate genes including adenosine deaminase-RNA-specific, caspase 5, interferon consensus sequence binding protein 1, interferon-induced protein 44, phosphoinositide-3-kinase catalytic gamma polypeptide and transporter 2 ATP-binding cassette subfamily B genes. We further applied the artificial neural network algorithms with these seven single nucleotide polymorphisms, viral genotype, viral load, age and gender information to build tools for predicting the responsiveness of interferon. Based on the fivefold cross-validation method to evaluate the performance, the model achieved a high success rate of prediction.


CONCLUSIONS
We demonstrated that a trained artificial neural network model is a promising method for providing the inference from factors such as single nucleotide polymorphisms, viral genotype, viral load, age and gender to the responsiveness of interferon.
Lin
Eugene
E
Vita Genomics, Inc., 7 Fl., No. 6, Sec. 1, Jung-Shing Road, Wugu Shiang, Taipei, Taiwan. eugene.lin@vitagenomics.com
Hwang
Yuchi
Y
Wang
Shu-Ching
SC
Gu
Z John
ZJ
Chen
Ellson Y
EY
D000375:Aging / Q000502:physiology; D000465:Algorithms; D000998:Antiviral Agents / Q000627:therapeutic use*; D004359:Drug Therapy, Combination; D005544:Forecasting; D005838:Genotype; D016174:Hepacivirus / Q000235:genetics; D019698:Hepatitis C, Chronic / Q000188:drug therapy*; D006801:Humans; D007155:Immunologic Factors / Q000494:pharmacology; D007372:Interferons / Q000627:therapeutic use*; D016571:Neural Networks, Computer; D020641:Polymorphism, Single Nucleotide; D015203:Reproducibility of Results; D012254:Ribavirin / Q000627:therapeutic use; D012727:Sex Characteristics; D015398:Signal Transduction / Q000187:drug effects; D019562:Viral Load
D000998:Antiviral Agents; D007155:Immunologic Factors; D012254:Ribavirin; D007372:Interferons