Abstract
MISTIC (mutual information server to infer coevolution) is a web server for graphical representation of the information contained within a MSA (multiple sequence alignment) and a complete analysis tool for Mutual Information networks in protein families. The server outputs a graphical visualization of several information-related quantities using a circos representation. This provides an integrated view of the MSA in terms of (i) the mutual information (MI) between residue pairs, (ii) sequence conservation and (iii) the residue cumulative and proximity MI scores. Further, an interactive interface to explore and characterize the MI network is provided. Several tools are offered for selecting subsets of nodes from the network for visualization. Node coloring can be set to match different attributes, such as conservation, cumulative MI, proximity MI and secondary structure. Finally, a zip file containing all results can be downloaded. The server is available at http://mistic.leloir.org.ar. In summary, MISTIC allows for a comprehensive, compact, visually rich view of the information contained within an MSA in a manner unique to any other publicly available web server. In particular, the use of circos representation of MI networks and the visualization of the cumulative MI and proximity MI concepts is novel.
Highlights
Multiple sequence alignments (MSA) of homologous proteins carry at least two types of information: one given by the conservation of amino acids at certain positions, and another given by the interrelationship between two or more positions
Dunn et al [14] is applied to reduce the background mutual information signal for each pair of residues, and the Mutual Information (MI) scores are translated into MI z-scores by comparing the MI values for each pair of position with a distribution of prediction scores obtained from a large set of permutated versions of the MSA
We have developed an interactive web server providing the end users with a highly intuitive view of the information contained within an MSA
Summary
Multiple sequence alignments (MSA) of homologous proteins carry at least two types of information: one given by the conservation of amino acids at certain positions, and another given by the interrelationship between two or more positions. If a reference structure is available, the methods described in [6] and [7] provide a static image with the coevolving residue pairs highlighted in the structure In contrast to these tools, the MISTIC (mutual information server to infer coevolution) server offers an interactive platform to analyze and visualize MI and distance networks, perform network analyses, filtering results by different scores simultaneously at both nodes and edges and different options for graphical representation of the information contained within an MSA. The MISTIC server allows to integrate sequence and structure information contained in an MSA in a comprehensive, compact, visually rich manner that enables the user to extract essential information in terms of networks, conservation and structure for any subset of residues of interest guiding the identification of functionally important residues in a protein.
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