An Artificial Neural Network Approach to the Drug efficacy of Interferon Treatments

Abstract

Introduction: 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. Materials and 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 γ 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. Conclusion: 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.

Keywords: :

• chronic hepatitis C
• interferon
• pharmacogenomics
• ribavirin
• single nucleotide polymorphisms

Acknowledgements

The authors extend their sincere appreciation to Vita Genomics, Inc. for funding the research and to Dr Pei-Jer Chen of the Hepatitis Research Center, National Taiwan University, Dr You-Chen Chao of the Tri-Service General Hospital, Dr Ming-Lung Yu of the Kaohsiung Medical University Hospital, and Dr Chuan-Mo Lee of the Kaohsiung Chang-Gung Memorial Hospital for research collaboration.

Additional information

Funding

The authors extend their sincere appreciation to Vita Genomics, Inc. for funding the research and to Dr Pei-Jer Chen of the Hepatitis Research Center, National Taiwan University, Dr You-Chen Chao of the Tri-Service General Hospital, Dr Ming-Lung Yu of the Kaohsiung Medical University Hospital, and Dr Chuan-Mo Lee of the Kaohsiung Chang-Gung Memorial Hospital for research collaboration.