The influence of gapped positions in multiple sequence alignments on secondary structure prediction methods.
All currently leading protein secondary structure prediction methods use a multiple protein sequence alignment to predict the secondary structure of the top sequence. In most of these methods, prior to prediction, alignment positions showing a gap in the top sequence are deleted, consequently leading to shrinking of the alignment and loss of position-specific information. In this paper we investigate the effect of this removal of information on secondary structure prediction accuracy. To this end, we have designed SymSSP, an algorithm that post-processes the predicted secondary structure of all sequences in a multiple sequence alignment by (i) making use of the alignment's evolutionary information and (ii) re-introducing most of the information that would otherwise be lost. The post-processed information is then given to a new dynamic programming routine that produces an optimally segmented consensus secondary structure for each of the multiple alignment sequences. We have tested our method on the state-of-the-art secondary structure prediction methods PHD, PROFsec, SSPro2 and JNET using the HOMSTRAD database of reference alignments. Our consensus-deriving dynamic programming strategy is consistently better at improving the segmentation quality of the predictions compared to the commonly used majority voting technique. In addition, we have applied several weighting schemes from the literature to our novel consensus-deriving dynamic programming routine. Finally, we have investigated the level of noise introduced by prediction errors into the consensus and show that predictions of edges of helices and strands are half the time wrong for all the four tested prediction methods.
Simossis
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VA
Bioinformatics Section, Faculty of Sciences, Vrije Universiteit, De Boelelaan 1081A, 1081 HV Amsterdam, The Netherlands.
Heringa
J
J
D000465:Algorithms; D000595:Amino Acid Sequence; D019295:Computational Biology / Q000379:methods; D017124:Conserved Sequence; D030562:Databases, Protein; D008969:Molecular Sequence Data; D017433:Protein Structure, Secondary; D011506:Proteins / Q000737:chemistry* / Q000145:classification; D016415:Sequence Alignment / Q000379:methods; D017386:Sequence Homology, Amino Acid
D011506:Proteins