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


CONCLUSIONS
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.
Huang
Tao
T
Key Laboratory of Systems Biology, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, Shanghai, 200031, PR China. huangtao@sibs.ac.cn
Tu
Kang
K
Shyr
Yu
Y
Wei
Chao-Chun
CC
Xie
Lu
L
Li
Yi-Xue
YX
D015415:Biomarkers / Q000097:blood; D044383:Black People / Q000235:genetics; D016000:Cluster Analysis; D020869:Gene Expression Profiling; D005786:Gene Expression Regulation; D006801:Humans; D007372:Interferons / Q000627:therapeutic use*; D008954:Models, Biological; D051920:NK Cell Lectin-Like Receptor Subfamily D / Q000235:genetics / Q000378:metabolism; D020411:Oligonucleotide Array Sequence Analysis; D015203:Reproducibility of Results; D053221:TNF-Related Apoptosis-Inducing Ligand / Q000235:genetics / Q000378:metabolism; D013997:Time Factors; D044465:White People / Q000235:genetics; D001741:Black or African American
D015415:Biomarkers; D051920:NK Cell Lectin-Like Receptor Subfamily D; D053221:TNF-Related Apoptosis-Inducing Ligand; C505653:TNFSF10 protein, human; D007372:Interferons