PRESNP: Prediction of the Effects of non-synonymous SNPs on Protein Functions in Plants

Non-synonymous SNP (nsSNP) affects protein functions by amino acid substitution, although not all nsSNPs have the same effect on protein functions. Methods to predict the effect of nsSNP on protein function are of importance to identify nsSNP that have large effect. Evolutionary conservation of amino acids provides information about functional sites in a protein sequence. Amino acids that remain unchanged or are changed only to similar amino acids over long evolutionary times tend to be important to protein function, and nsSNPs at those conserved sites may often change protein functions. We introduce a web application, PRESNP, that predicts plant-specific functional effects of nsSNP based on the conservation profile of amino acids among distantly related plant species. PRESNP calculates a Functional Index Score (FIS) for every nsSNP based on multiple alignment of orthologous protein sequences of more than 30 plant species and reports the protein domain in which each nsSNP resides. Tests based on empirical EMS (Ethyl methanesulfonate) mutagenesis data in Arabidopsis show that PRESNP produces better predictions than any available protein substitution matrices, and shows more specificity than PolyPhen2 and SIFT. Future improvements may include 1) Combining existing structural and epistasis information in plant species into the prediction. 2) Replacing relational database (MySQL) with graph database (Neo4j) to achieve better performance. Currently, PRESNP is with limited access at http://snps.pgml.uga.edu/snpdb/nsSNP/.