Best ortholog/inparalog detection between human genes and species from different clades

Question

[Juan Cordero]

Hi,

I would like to find the orthologs/inparalogs for a set of human genes wide range of species concerning evolutionary distance: bacteria/archaea, fungi, plants...

Initially I've thought of a pairwise method such as Inparanoid, but its code performance is not good enough for a large number of proteomes (unless there's another version suitable for MPI or multithreading). I could use other methods based on groups of orthologs (OGs), but I am not quite interested in OGs, since I want to map human genes to distant and closer species/groups.

Any suggestions are very wellcome!

Thanks a lot in advance

[Jean-Karim Heriche]

Because of the definition of orthology and paralogy, building a phylogenetic tree is the proper way to go but that's usually computationally expensive. The main strategy to avoid this is to rely on pairwise alignment and clustering (e.g. OrthoMCL, COG, InParanoid ...). However, without building a phylogenetic tree, detection of inparalogs may be difficult/inaccurate and distant homologies are hard to detect with pairwise alignments. For some ideas on how to proceed, have a look at the TreeFam paper, the approach is used by EnsEMBL so it seems scalable enough. For any serious phylogeny work, you would need a compute farm. My suggestion would be to start from some existing resource and add the missing pieces. For example, you could start from existing Treefam trees and add the genes from the missing species.

Answer 1

[Rohit]

Proteinortho is designed to find orthologs and paralogs, just use the Poff-extension which uses annotations to make sure that false-positives are reduced. It is multi-threaded, but the run-time depends on the number of species you run it with. Another option is the biomart of ensembl if you are working on model species, just go for the multi-species comparison in the filters