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Splicing Enhancer Scoring in ISCAN. Overview. Method SC35 splicing enhancer WMM (SELEX experiments by M. Zhang & A. Krainer, CHSL) 6-base long pattern Training set “Clean†set of 6051 Refseq genes (no alternative splicing) Results
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Overview • Method • SC35 splicing enhancer WMM (SELEX experiments by M. Zhang & A. Krainer, CHSL) • 6-base long pattern • Training set • “Clean” set of 6051 Refseq genes (no alternative splicing) • Results • Introns are enriched in even-overlapped (by 2 and 4, bases) hits to SC35 WMM • Exons are enriched in hits overlapping by 3 bases
Deriving Splicing Enhancer Score • Let • n2 = count of 2-base overlaps, • n3 = count of 3-base overlaps, • d = n2 – n3 • Use distribution P(d) from the training set and a null model (e.g., randomized introns and exons) to derive the score
Problems (and workarounds) • P(d) depends on the length distribution • Use separate null models for exons and introns, or • 2-dimensional distribution P(d, L) • Does not work for geometric intron length model • Requires knowledge of intron length to compute the score • Whenever in exonic state, take upstream intron (length known) and score it. Add result to the exon score.