Splicing Exons: A Eukaryotic Challenge to Gene Prediction

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Splicing Exons A Eukaryotic Challenge to Gene
Prediction

• Ian McCoy

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Gene Prediction

• Genes must be identified to make the genome
  useful
• Computational Problem Take a seemingly random
  sequence of characters, millions or billions of
  bases long, and find the genes.

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A Serious Complication

• Only 3 of the human genome contains genes

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Similarity-Based Approach

• Instead of looking for a gene for a target
  protein directly, use a protein in a related
  organism.
• Find all local similarities between a genomic
  sequence and the target protein sequence.
• All substrings that exhibit a certain level of
  similarity will be called putative exons.

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Exon-Chaining Problem

• Use brute force to generate a set of putative
  exons.
• Represent each exon with three parameters
  (l,r,w).
• Find a maximum set of nonoverlapping putative
  exons.

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Formulate as Graph Problem

• Create a graph G with 2n verticies n vertices
  are starting(left) positions of exons and n
  vertices are ending(right) positions of exons.
• The set of left and right interval ends is sorted
  into increasing order.
• There are edges between each li and ri of weight
  wi for I from 1 to n and 2n-1 additional edges
  of weight 0 connecting adjacent vertices.

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Input A set of weighted intervals (putative
exons) Output The length of the maximum chain of
intervals from this set
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Dynamic Programming Algorithm

• ExonChaining (G, n) //Graph, number of intervals
• for i ? 1 to 2n
• si ? 0
• for i ? 2 to 2n
• if vertex vi in G corresponds to right end of
  the interval I
• j ? index of vertex for left end of the
  interval I
• w ? weight of the interval I
• sj ? max sj w, si-1
• else
• si ? si-1
• return s2n

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Shortcomings

• A large number of short exons will decrease the
  efficacy of our method for finding putative
  exons.
• Exons may be out of order.

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Any Questions?

• Jones, Neil C., and Pavel A. Pevzner. An
  Introduction to Bioinformatics Algorithms.
  Cambridge MIT Press, 2004. (p.200-203)