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The 5th Transactions on Computational Systems Biology volume, edited by Gordon Plotkin, features carefully selected and enhanced contributions initially presented at the 2005 IEEE International Conference on Granular Computing. The 9 papers selected for this special issue discuss various aspects of computational methods, algorithm 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.