JProfileGrid Facilitates Visual Exploration of dTIM Mutations within the Context of a Family Alignment
ProfileGrids are a visual representation of multiple sequence alignments (MSAs) that reduce an alignment to a matrix, color-shaded according to the residue frequency in the MSA. ProfileGrids readily facilitate the visualization of overall conservation, the entire details of residue distributions, and highlighting differences of one sequence relative to the entire MSA. For my 2013 BioVis Data Contest submission, this movie shows how I compare the yeast (ScTIM) and dTIM homologs to the entire MSA to predict driver and passive mutations. I first compared ScTIM to the MSA and a consensus sequence with the assumption that any residues unique to ScTIM in a cluster of conserved residues may be important for ScTIM function. I identified such a residue at MSA position 102 where the consensus residue is glutamate (shared by dTIM) but ScTIM has lysine. I postulate that this is a driver mutation knocking out TIM activity. I used another homolog (TPIS_CANGA) also containing 102-lys to identify potential passive mutations. If both dTIM and TPIS_CANGA have the same sequence at positions that are different from ScTIM, then I make the assumption that these are dTIM passive mutations. I identified such a mutation at MSA position 12 which is threoine in both dTIM and TPIS_CANGA but serine in ScTIM. Reiterating this procedure over the roughly 100 mutations between ScTIM and dTIM may identify more passive mutations. In summary, the interactive JProfileGrid software viewer interactively allows one to dissect alignments to understand structure and function. 2013 BioVis Data Contest website link below.