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Updated: Jan 22, 2026

Demonstration of the Sequence Alignment to Predict Across Species Susceptibility Tool for Rapid Assessment of Protein Conservation
Published on: February 10, 2023
Local sequence alignments with monotonic gap penalties
1SmithKline-Beecham Pharmaceuticals R & D, New Frontiers Science Park (North),3rd Avenue, Harlow CM19 5AW, UK. Richard.Mott@well.ox.ac.uk
Motivation:
Sequence alignments obtained using affine gap penalties are not always biologically correct, because the insertion of long gaps is over-penalised. There is a need for an efficient algorithm which can find local alignments using non-linear gap penalties.
Results:
A dynamic programming algorithm is described which computes optimal local sequence alignments for arbitrary, monotonically increasing gap penalties, i.e. where the cost g(k) of inserting a gap of k symbols is such that g(k) >/= g(k-1). The running time of the algorithm is dependent on the scoring scheme; if the expected score of an alignment between random, unrelated sequences of lengths m, n is proportional to log mn, then with one exception, the algorithm has expected running time O(mn). Elsewhere, the running time is no greater than O(mn(m+n)). Optimisations are described which appear to reduce the worst-case run-time to O(mn) in many cases. We show how using a non-affine gap penalty can dramatically increase the probability of detecting a similarity containing a long gap.
Availability:
The source code is available to academic collaborators under licence.
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