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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.