BLAST

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Copyright © 2012 O’Reilly & Associates, Inc. All rights reserved.

Further Reading

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53

Aligning Transcripts to Genomic Sequence

Determining the correct exon-intron structure of genes isn’t always easy. One very

successful approach is to align transcripts back to their origin in a genome. How-

ever, this isn’t as simple as it may appear. Several solutions to this problem use either

global or local techniques.

A global alignment between a transcript and a genomic sequence is expected to have

huge gaps corresponding to the introns. In eukaryotic genomes, such as the human

genome, exons may account for only 1 to 2 percent of a genome. As a result, the gap

scores may completely dominate the scoring function, and the alignment may be of

little consequence. If the gap costs are too low, the alignment may spread out, and

exons may not be faithfully aligned. These problems are largely solved by gapping

with double affine penalties, but there are still potential problems with short exons

and introns.

A standard local alignment between a transcript and a genome typically identifies the

longest exon as the maximum scoring pair. This isn’t as useful, but many local align-

ment algorithms, like BLAST, produce more than one alignment. With these vari-

ants, mapping a transcript back to a genome is simply a matter of chaining the

individual alignments together. This ...