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

<p>Abstract</p> <p>Background</p> <p>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.</p> <p>Methods</p> <p>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.</p> <p>Results</p> <p>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.</p> <p>Conclusion</p> <p>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.</p

Autoregressive Kernels For Time Series

We propose in this work a new family of kernels for variable-length time series. Our work builds upon the vector autoregressive (VAR) model for multivariate stochastic processes: given a multivariate time series x, we consider the likelihood function p_{\theta}(x) of different parameters \theta in the VAR model as features to describe x. To compare two time series x and x', we form the product of their features p_{\theta}(x) p_{\theta}(x') which is integrated out w.r.t \theta using a matrix normal-inverse Wishart prior. Among other properties, this kernel can be easily computed when the dimension d of the time series is much larger than the lengths of the considered time series x and x'. It can also be generalized to time series taking values in arbitrary state spaces, as long as the state space itself is endowed with a kernel \kappa. In that case, the kernel between x and x' is a a function of the Gram matrices produced by \kappa on observations and subsequences of observations enumerated in x and x'. We describe a computationally efficient implementation of this generalization that uses low-rank matrix factorization techniques. These kernels are compared to other known kernels using a set of benchmark classification tasks carried out with support vector machines

Supervised learning of short and high-dimensional temporal sequences for life science measurements

The analysis of physiological processes over time are often given by spectrometric or gene expression profiles over time with only few time points but a large number of measured variables. The analysis of such temporal sequences is challenging and only few methods have been proposed. The information can be encoded time independent, by means of classical expression differences for a single time point or in expression profiles over time. Available methods are limited to unsupervised and semi-supervised settings. The predictive variables can be identified only by means of wrapper or post-processing techniques. This is complicated due to the small number of samples for such studies. Here, we present a supervised learning approach, termed Supervised Topographic Mapping Through Time (SGTM-TT). It learns a supervised mapping of the temporal sequences onto a low dimensional grid. We utilize a hidden markov model (HMM) to account for the time domain and relevance learning to identify the relevant feature dimensions most predictive over time. The learned mapping can be used to visualize the temporal sequences and to predict the class of a new sequence. The relevance learning permits the identification of discriminating masses or gen expressions and prunes dimensions which are unnecessary for the classification task or encode mainly noise. In this way we obtain a very efficient learning system for temporal sequences. The results indicate that using simultaneous supervised learning and metric adaptation significantly improves the prediction accuracy for synthetically and real life data in comparison to the standard techniques. The discriminating features, identified by relevance learning, compare favorably with the results of alternative methods. Our method permits the visualization of the data on a low dimensional grid, highlighting the observed temporal structure

Class prediction from time series gene expression profiles using dynamical systems kernels

We present a kernel-based approach to the classification of time series of gene expression profiles. Our method takes into account the dynamic evolution over time as well as the temporal characteristics of the data. More specifically, we model the evolution of the gene expression profiles as a Linear Time Invariant (LTI) dynamical system and estimate its model parameters. A kernel on dynamical systems is then used to classify these time series. We successfully test our approach on a published dataset to predict response to drug therapy in Multiple Sclerosis patients. For pharmacogenomics, our method offers a huge potential for advanced computational tools in disease diagnosis, and disease and drug therapy outcome prognosis