New tool: Ortholog Residue Substitution Scanner

We wanted a way of searching for amino acid substitutions across orthologs so we could find versions that replaced a cysteine residue for something else, and see the amino acid context of that change so we could engineer a hybrid protein with the substitution in its proper context. We broadened this so one could use it to see if, say, a disease variant is tolerated in an ortholog, and then see the discrete 7-residue context it sits in.

The result is the Ortholog Residue Substitution Scanner, a web app for checking whether specific residue positions in a protein are conserved or substituted across eukaryotic orthologs — sampled as broadly across the eukaryotic tree as practical: fungi, plants, protists, and invertebrates alongside the usual vertebrate comparisons, not just close relatives. It works by querying OrthoDB, a database of pre-computed orthologous gene groups, then pairwise-aligning every member of the relevant group back to your query sequence (Biopython, BLOSUM62) to report each tracked position as conserved, substituted, or absent (a gap) in that ortholog. Species are also classified to their taxonomic phylum, so results can be scanned for how broadly — or narrowly — conservation actually holds.

The app runs locally as a standalone desktop application (no server, no data leaves your machine) and is free to download and use.

Get it: github.com/RobertPiper/Ortholog-Residue-Substitution-Scanner