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With advances in biotechnologies, large-scale biological data has been and will continue to be produced. These large-scale biological data contain insightful information for understanding the mechanism of biological systems and have proven useful in the diagnosis, treatment, and drug design for genomic-alerted diseases. In this special section, five papers in their significantly extended versions were selected from the papers presented at the IEEE Conference on Bioinformatics and Biomedicine (BIBM), 2009. These papers present recent research in bioinformatics and systems biology to make sense from large-scale biological data.