I've been using HUMAnN2 to go from human-removed microbiome shotgun metagenomic reads to HUMAnN2 attribute vectors with coverage and abundance values. The resulting attributes have identifiers that have the following structure: HISDEG-PWY: L-histidine degradation I|g__Streptococcus.s__Streptococcus_sanguinis where Streptococcus sanguinis is the taxonomic unit and HISDEG-PWY is the metabolic unit.
My question is how actually two separate questions:
(1) Is there a a database available through MetaCyc that has orthologs where one can blast against like KEGG orthologs? Which one would I download for this type of functionality.
From the url: https://metacyc.org/download.shtml
We provide the BioCyc databases (such as EcoCyc and MetaCyc) as collections of data files in several alternative formats including the following.
BioPAX format
Pathway Tools attribute-value format
Pathway Tools tabular format
SBML format
Gene Ontology annotations (EcoCyc only)
(2) How does HUMAnN2 go from read -> MetaCyc pathway & read -> species?
I know they use metaphlan2 in the backend which is how they get the species but how do they know which MetaCyc pathway to assign the protein?
1 answer
For the 1st question according to their webpage: (https://bitbucket.org/biobakery/humann2/wiki/Home) *UniRef database provides gene family definitions *MetaCyc provides pathway definitions by gene family
It seems like they map to Uniprot, from there they get the "gene family" name and then they obtain the MetaCyc annotation. Let's say you already mapped to UniProt and get the protein id "P01189" (https://www.uniprot.org/uniprot/P01189) if you get the gene name from there "Name:POMC" you can easily obtain its description in the humancyc (instead of metacyc because for this example is a human protein): https://biocyc.org/gene?orgid=HUMAN&id=ENSG00000115138-MONOMER
I believe it works like that, so the way to go would be to map/blast to UniProt first I guess, thats my opinion at least.
You can download the database of Uniref50 for instance by following their tutorial: https://bitbucket.org/biobakery/humann2/wiki/Home#markdown-header-download-a-translated-search-database
Then you get the "uniref50_annotated.1.1.dmnd" and you can convert it to "fasta": diamond getseq -d uniref50_annotated.1.1.dmnd
Or downloading the fasta file directly from UniProt: https://www.uniprot.org/downloads
Anyway to have a more accurate answer you could also put your question in humann forum as well: https://groups.google.com/forum/#!forum/humann-users
Greetings
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