th The 4 edition of the InternationalSymposium on BioinformaticsResearchand Applications (ISBRA 2008) was held on May 6-9, 2008 at Georgia State U- versity in Atlanta, Georgia. The symposium provides a forum for the exchange of ideas and results among researchers, developers, and practitioners working on all aspects of bioinformatics and computational biology and their applications. The technical program of the symposium included 35 contributed papers, selected by the Program Committee from a number of 94 full submissions - ceived in response to the call for papers. The technical program also included six papers contributed to the First International Workshop on Optimal Data Mining in Gene Expression Analysis (ODGEA 2008), which was held in c- junction with ISBRA 2008. In addition to the contributed papers, the sym- sium included tutorials and poster sessions and featured invited keynote talks by six distinguished speakers. Andrew Scott Allen from Duke University and Dan Nicolae from the University of Chicago spoke on novel analysis methods for genome-wide association studies; Kenneth Buetow, director of the National Cancer Institute Center for Bioinformatics, spoke on the cancer Biomedical - formatics Grid; Andrey Gorin from Oak Ridge National Laboratory spoke on peptide identi?cation from mass spectrometry data; Yury Khudyakov from the Center for Disease Control and Prevention spoke on integrative viral molecular epidemiology; and Kwok Tsui from Georgia Institute of Technology spoke on data mining and statistical methods for analyzing microarray experiment