MicroRNA - MicroRNA The Computational Challenge...

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MicroRNA The Computational Challenge Bioinformatics Seminar, March 9, 2005 By Yaron Levy
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Tree of RNA Types
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miRNA Biological Process
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Micro RNA – Computational Approach Problem 1: Finding putative microRNA from a sequence Horesh et al, using suffix trees data structure Problem 2: Computing secondary structure of a given sequence Zuker & Steigler, minimum free energy, using dynamic programming Problem 3: miRNA predicting algorithms Lim et al, MiRscan Problem 4: Predicting miRNA target genes Lewis et al, TargetScan
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Problem 1 Find these
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Problem 1: Finding putative microRNA from a sequence A naïve idea: slide a “window” of size L over the sequence of size N, looking for stems of size S. Computationally O(NL+NS) – too much A better approach – using a suffix tree.
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S = M A L A Y A L A M $ 1 2 3 4 5 6 7 8 9 10 $ YALAM$ M $ ALAYALAM$ $M A AL LA 6 2 8 4 7 3 1 9 5 10 What is a suffix tree?
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Suffix tree properties For a string S of length n , there are n leaves and at most n internal nodes. therefore requires only linear space Each leaf represents a unique suffix. Concatenation of edge labels from root to a leaf spells out the suffix. Each internal node represents a distinct common prefix to at least two suffixes.
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Finding a (short) Pattern in a (long) String 1. Build a suffix tree of the string. 2. Starting from the root, traverse a path matching characters of the pattern. 3. If stuck, pattern not present in string. Otherwise, each leaf below gives a position of the pattern in the string.
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Find “ALA” $ YALAM$ M $ ALAYALAM$ M$ A AL LA 6 2 8 4 7 3 1 9 5 10 Two matches - at 6 and 2 Finding a Pattern in a String
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Generalized Suffix Tree $ O ND W I $OG D $OGI OW$ $W $ INDOW$ (2, 3) (1, 4) (2, 5) (2, 4) (2, 1) (1, 2) (2, 2) (1, 3) (1, 5) (2, 6) (1, 6) (1, 1) (1, 7) (2, 7) WINDOW$ INDIGO$ 1234567 1234567
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Horesh et al – using a generalized suffix tree for finding putative microRNA’s Assumptions: At least a triple repeat is necessary: 2 for the stems of the hairpin – close to each other in the sequence, and as inverted repeat of each other The rest are target genes – can be anywhere The repeats must be fully matched – no mismatches are allowed This is more of a constraint
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Construct a generalized suffix tree of the original sequence and the inverted repeat sequence. Preprocess the suffix tree for calculating: Length of suffixes Number of repeats Index of suffix in sequence With these attributes for each node, along with the indices of the suffixes in the sequence, it is possible to find the requested triple (or more) repeats. Computationally efficient O(N)
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MicroRNA - MicroRNA The Computational Challenge...

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