In SIFT dbSNP, separate scores are returned for orthologs and homologs. I thought an ortholog is a homolog, so I am a little confused. In the paper by Ng & Henikoff, they say:
"Although SIFT can choose sequences automatically, better prediction results may be obtained when all of the sequences that are provided are orthologous to the query protein. This is because inclusion of paralogous sequences confounds prediction at residues conserved only among the orthologues."
So, do homologs include both orthologs and paralogs?
4 answers
In SIFT dbSNP, try to use the prediction based on orthologs. If there is a low-confidence warning, then use the prediction based on homologs. The "orthologs" used for prediction in SIFT's dbSNP table are not true orthologs in the sense that we did not build a tree, but rather took the best hits of a genome-genome blast search, which is considered a cheap computational way to get orthologs.
I have moved the SIFT website to http://sift-dna.org and you can also submit your questions there. At the new website, only one prediction is returned for dbSNP to ensure compatibility with the genome predictions.
If two genes are separated by a speciation event, then they are orthologous and if they are separated by a duplication event, they are paralogous. Both are homologous nonetheless. What the authors mean is that you only compare orthologous sequences mostly...
Yes, as I understand the set of homologs [of one espice against other] include the set of orthologs (at birds eye, similar sequence and similar function) PLUS the set of paralogs (similar sequence but NOT similar function).
If I am mistake, please that someone corrects me (I am software developer so ... :) ).
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