Predicting viral exposure response from modeling the changes of co-expression networks using time series gene expression data

Deciphering the relationship between clinical responses and gene expression profiles may shed light on the mechanisms underlying diseases. Most existing literature has focused on exploring such relationship from cross-sectional gene expression data. It is likely that the dynamic nature of time-series gene expression data is more informative in predicting clinical response and revealing the physiological process of disease development. However, it remains challenging to extract useful dynamic information from time-series gene expression data.

We propose a statistical framework built on considering co-expression network changes across time from time series gene expression data. It first detects change point for co-expression networks and then employs a Bayesian multiple kernel learning method to predict exposure response. There are two main novelties in our method: the use of change point detection to characterize the co-expression network dynamics, and the use of kernel function to measure the similarity between subjects. Our algorithm allows exposure response prediction using dynamic network information across a collection of informative gene sets. Through parameter estimations, our model has clear biological interpretations. The performance of our method on the simulated data under different scenarios demonstrates that the proposed algorithm has better explanatory power and classification accuracy than commonly used machine learning algorithms. The application of our method to time series gene expression profiles measured in peripheral blood from a group of subjects with respiratory viral exposure shows that our method can predict exposure response at early stage (within 24 h) and the informative gene sets are enriched for pathways related to respiratory and influenza virus infection.

The biological hypothesis in this paper is that the dynamic changes of the biological system are related to the clinical response. Our results suggest that when the relationship between the clinical response and a single gene or a gene set is not significant, we may benefit from studying the relationships among genes in gene sets that may lead to novel biological insights.