MISTIC: MUTUAL INFORMATION SERVER TO INFER COEVOLUTION

FRANCO L. SIMONETTI; ELIN TEPPA; ARIEL CHERNOMORETZ; MORTEN NIELSEN; CRISTINA MARINO BUSLJE

Berlín

Congreso; 3DSIG. Structural Bioinformatics and COmputational Biophysics; 2013

ISMB-ECCB

Identifying functionally important residues of proteins has long been investigated using multiple sequence alignments. Besides studying the conserved residues, another information rich approach is to examine the correlated mutational pattern between columns of the alignment. Mutual information (MI) from information theory can be used to analyze this type of covariation. We have previously developed an MI algorithm that corrects several known biases in the MI signal, such as phylogeny, sequence redundancy and low counts (1-2). Here we present MISTIC, a publicly available Mutual Information Server To Infer Coevolution that brings covariation analysis closer to non-computational biologists with a friendly-user interface and an interactive view of the results. MISTIC uses a multiple sequence alignment as the basis for calculating mutual information and several residue-based scores, and can also integrate structural data when a PDB structure is provided. The server outputs a graph with several information-related quantities using a circos representation. This offers an integrated view of the information contained in the multiple sequence alignment in terms of mutual information between residue-pairs, sequence conservation and cumulative and proximity MI scores. Furthermore, analysis and characterization of the MI network can be done using an interactive interface which includes network-to-structure mapping and several other network oriented tools (figure 1).