Improved Assay-dependent Searching of Nucleic Acid Sequence Databases

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Improved Assay-dependent Searching of Nucleic
Acid Sequence Databases
Jason Gans Los Alamos National Laboratory
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O(N2) Thermodynamic alignment

1. Define a reduced pair-wise free energy
   function, whose exact O(N2) minimum
   energy alignment approximates the minimum energy
   alignment of the near neighbor free energy
   function,
2. Determine free parameters by simulated
   annealing-based minimization of evaluated
   at the alignments produced by

Aligned bases
Gap regions
Temperature
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Comparison between approximate O(N2) alignment
and O(N3) alignment produced by DINAMelt Server
DDG kcal mol-1
0.7 kcal mol-1
1.9 ºC
DTm ºC
Temperature ºC
Markham and Zuker (2005) Nucleic Acids Research,
33, W577-W581
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Identification of STS primer binding sites in the
human genome (DG match criteria)
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ThermonucleotideBLAST implements target splitting
and adaptive segmentation
Target segmentation
Target query segmentation
t targets q queries w workers S/H
time to search one query
Cost of target segmentation per worker
Cost of target and query segmentation per worker
time to load and hash one target
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T1000gtgtQ100gtgtW10
T1000gtgtW100gtgtQ10
Q1000gtgtT100gtgtW10
Q1000gtgtW100gtgtT10
W200gtQ100gtgtT10
W200gtgtT100gtgtQ10