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The 5th Transactions on Computational Systems Biology collects carefully chosen and enhanced contributions initially presented at the 2005 IEEE International Conference on Granular Computing held in Beijing, China, in July 2005. The 9 papers in this special issue cover various aspects of computational methods, algorithms and techniques in bioinformatics such as gene expression analysis, biomedical literature mining and natural language processing, protein structure prediction, biological database management and biomedical information retrieval.