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Time-course high-throughput gene expression data are emerging in genomic and translational medicine. Extracting interesting time-course patterns from a patient cohort can provide biological insights for further clinical research and patient treatment. We propose principal trend analysis (PTA) to extract principal trends of time-course gene expression data from a group of patients, and identify genes that make dominant contributions to the principal trends. Through simulations, we demonstrate the utility of PTA for dimension reduction, time-course signal recovery and feature selection with high-dimensional data. Moreover, PTA derives new insights in real biological and clinical research. We demonstrate the usefulness of PTA by applying it to longitudinal gene expression data of a circadian regulation system and burn patients. These applications show that PTA can extract interesting time-course trends with …