Nucleic Acids Research, Vol 27, Issue 19 3899-3910, Copyright © 1999 by Oxford University Press
N Stojanovic, L Florea, C Riemer, D Gumucio, J Slightom, M Goodman, W Miller and R Hardison
Conserved segments in DNA or protein sequences are strong candidates for
functional elements and thus appropriate methods for computing them need to
be developed and compared. We describe five methods and computer programs
for finding highly conserved blocks within previously computed multiple
alignments, primarily for DNA sequences. Two of the methods are already in
common use; these are based on good column agreement and high information
content. Three additional methods find blocks with minimal evolutionary
change, blocks that differ in at most k positions per row from a known
center sequence and blocks that differ in at most k positions per row from
a center sequence that is unknown a priori. The center sequence in the
latter two methods is a way to model potential binding sites for known or
unknown proteins in DNA sequences. The efficacy of each method was
evaluated by analysis of three extensively analyzed regulatory regions in
mammalian beta-globin gene clusters and the control region of bacterial
arabinose operons. Although all five methods have quite different
theoretical underpinnings, they produce rather similar results on these
data sets when their parameters are adjusted to best approximate the
experimental data. The optimal parameters for the method based on
information content varied little for different regulatory regions of the
beta- globin gene cluster and hence may be extrapolated to many other
regulatory regions. The programs based on maximum allowed mismatches per
row have simple parameters whose values can be chosen a priori and thus
they may be more useful than the other methods when calibration against
known functional sites is not available.
ARTICLES
Comparison of five methods for finding conserved sequences in multiple alignments of gene regulatory regions
Department of Computer Science and Engineering, The Pennsylvania State University, University Park 16802, USA.
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