Prognostic Prediction through Biclustering-Based Classification of Clinical Gene Expression Time Series

Abstract

Summary The constant drive towards a more personalized medicine led to an increasing interest in temporal gene expression analyzes. It is now broadly accepted that considering a temporal perspective represents a great advantage to better understand disease progression and treatment results at a molecular level. In this context, biclustering algorithms emerged as an important tool to discover local expression patterns in biomedical applications, and CCC-Biclustering arose as an efficient algorithm relying on the temporal nature of data to identify all maximal temporal patterns in gene expression time series. In this work, CCC-Biclustering was integrated in new biclustering-based classifiers for prognostic prediction. As case study we analyzed multiple gene expression time series in order to classify the response of Multiple Sclerosis patients to the standard treatment with Interferon-β, to which nearly half of the patients reveal a negative response. In this scenario, using an effective predictive model of a patient’s response would avoid useless and possibly harmful therapies for the non-responder group. The results revealed interesting potentialities to be further explored in classification problems involving other (clinical) time series.