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AgeWa: An integrated approach for Antisense Experiment design P.Arrigo(1), P.Romano(2), P.Scartezzini(3) (1) (2) CNR IIET, sezione di Genova e-mail: [email protected] Natl. Cancer Res.Institute, Genova,Italy (3) Dept of Neonatology, E.O Ospedali Galliera, Genova,Italy Structural and Functional Genomics Structural Genomics: Investigation of the biological functionality by using structural biology data ( cristallographic,NMR) Functional Genomics: Investigation of the gene function in its context (pathaway) starting from the outcome of structural Genomics Integrative approach for drug target validation Small molecule phenotype Expression pattern Knockouts Gene Disease 3D structure Polymorphism Orthologs Genome region Pathways Family members Species Function Antisense and Functional Genomics Genetic screening Candidate gene HTS Gene expression Data Integration Validation Antisense design Potential Antisense Target Pre mRNA splicing RNA targets mRNA transport 1. Cap Site 2. 3’ UTR 3. AUG downstream elements Splicing sites Dna targets Major groove Transcriptional inhibition Target Selection methods Optimal hybridisation site selection 1) Walk the gene 2) Combinatorial approach 3) Rnase H mapping 4) Secondary structure prediction 1) Tethered ASO 2) Triplex forming ASO Screening of Structured RNA binding motifs 3) Minimization of non specific binding 4) Empirical search AgeWa structure EST AgeWa Hybridisation simulator STS Remote search Local search Experimental Validation AgeWa Kernel Custom sequence Learning phase Complementary Data mining selected Sequence Tag Selection ASO selection rule Learning & Tag selection 1. Preprocessing phase ( segmentation of the custom sequence into the training set X and synaptic score matrix initialisation) 2. Learning phase Partition of the X dataset into Cj Classes by using a Winner Take All algorithm.