A comparative study of conservation and variation scores

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Abstract

Background: Conservation and variation scores are used when evaluating sites in a multiple sequence alignment, in order to identify residues critical for structure or function. A variety of scores are available today but it is not clear how different scores relate to each other.Results: We applied 25 conservation and variation scores to alignments from the Catalytic Site Atlas (CSA). We calculated distances among scores based on correlation coefficients, and constructed a dendrogram of the scores by average linking cluster analysis. The cluster analysis showed that most scores fall into one of two groups--substitution matrix based group and frequency based group respectively. We also evaluated the scores' performance in predicting catalytic sites and found that frequency based scores generally perform best.Conclusions: Conservation and variation scores can be classified into mainly two large groups. When using a score to predict catalytic sites, frequency based scores that also consider a background distribution are most successful. © 2010 Johansson and Toh; licensee BioMed Central Ltd.

Figures

  • Table 1 Pearson correlation of alignment size (N) and mean conservation score on the CSA dataset
  • Figure 1 Hierarchical clustering results. Dendrogram obtained from hierarchical clustering of average Spearman correlations on each alignment, using average linking. Each node is labeled by a probability value in percent, given by 1000 iterations of a bootstrap procedure.
  • Figure 2 Performance evaluation. Performance evaluation of catalytic site prediction. Lines show the performance measured by the AUC measure for subsets of the original dataset obtained by setting an upper limit on alignment size (ranging from 10 to 168 sequences in an alignment). The legend is sorted on score performance for the original dataset (equal to the right terminal values of the graph), and also shows the numerical AUC value for this case. Lines and score names are colored acccording to the clustering shown in Figure 1 as; red: cluster A, blue: cluster B, green: other scores.
  • Table 2 Example of ranking of a site
  • Table 3 Scoring methods at an alignment site k
  • Table 4 Notations used in Table 3

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CITATION STYLE

APA

Johansson, F., & Toh, H. (2010). A comparative study of conservation and variation scores. BMC Bioinformatics, 11. https://doi.org/10.1186/1471-2105-11-388

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