The prediction of interferon treatment effects based on time series microarray gene expression profiles

Tao Huang^*¹^,2 , Kang Tu^*¹^,2 , Yu Shyr³ , Chao-Chun Wei² , Lu Xie² and Yi-Xue Li¹^,2

¹Key Laboratory of Systems Biology, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, Shanghai, 200031, PR China

²Shanghai Center for Bioinformation Technology, Shanghai, 200235, PR China

³Cancer Biostatistics Center, Vanderbilt University, Nashville, 37232, USA

author email corresponding author email* Contributed equally

Journal of Translational Medicine 2008, 6:44doi:10.1186/1479-5876-6-44


Published:	9 August 2008

Abstract

Background

The status of a disease can be reflected by specific transcriptional profiles resulting from the induction or repression activity of a number of genes. Here, we proposed a time-dependent diagnostic model to predict the treatment effects of interferon and ribavirin to HCV infected patients by using time series microarray gene expression profiles of a published study.

Methods

In the published study, 33 African-American (AA) and 36 Caucasian American (CA) patients with chronic HCV genotype 1 infection received pegylated interferon and ribavirin therapy for 28 days. HG-U133A GeneChip containing 22283 probes was used to analyze the global gene expression in peripheral blood mononuclear cells (PBMC) of all the patients on day 0 (pretreatment), 1, 2, 7, 14, and 28. According to the decrease of HCV RNA levels on day 28, two categories of responses were defined: good and poor. A voting method based on Student's t test, Wilcoxon test, empirical Bayes test and significance analysis of microarray was used to identify differentially expressed genes. A time-dependent diagnostic model based on C4.5 decision tree was constructed to predict the treatment outcome. This model not only utilized the gene expression profiles before the treatment, but also during the treatment. Leave-one-out cross validation was used to evaluate the performance of the model.

Results

The model could correctly predict all Caucasian American patients' treatment effects at very early time point. The prediction accuracy of African-American patients achieved 85.7%. In addition, thirty potential biomarkers which may play important roles in response to interferon and ribavirin were identified.

Conclusion

Our method provides a way of using time series gene expression profiling to predict the treatment effect of pegylated interferon and ribavirin therapy on HCV infected patients. Similar experimental and bioinformatical strategies may be used to improve treatment decisions for other chronic diseases.