Help with understanding the identifier mapping tables in the backend of HUMAnN

Question

[O.rka]

I’m looking for the identifier mapping tables used in the backend for HUMAnN.

More specifically, the following if they are available:

UniRef50 -> EC UniRef50(or EC) -> KEGG KO EC -> MetaCyc pathway UniRef50 (EC or KO) -> KEGG pathway

I found some files here: site-packages/humann/data/pathways/

I have a few questions:

• Is it expected for one UniRef50 ID to map to more than one EC in some cases?

UniRef50_G6EMD2        {5.4.2.6, 2.7.1.41}
UniRef50_Q1J7L4        {5.4.2.6, 2.7.1.41}
UniRef50_T0UKK6        {5.4.2.6, 2.7.1.41}
UniRef50_X5NX36        {5.4.2.6, 2.7.1.41}

How is this handled in the backend? Does a UniRef50 hit for these count towards both or only one?

• I got ID mappings between pathways and rxns from data/pathways/metacyc_pathways. Many of these rxns do not have ECs and are not present in data/pathways/metacyc_reactions_level4ec_only.uniref.bz2. For example, the following:

list(pwy_to_rxns["PWY-2681"])
# ['RXN-4308',
#  'RXN-4305',
#  'RXN-4317',
#  'RXN-4310',
#  'RXN-4306',
#  'RXN-4314',
#  'RXN-4303',
#  'RXN-4307',
#  'RXN-4313',
#  'RXN-4312',
#  'RXN-4304']

pd.Series(rxn_to_ec)[list(pwy_to_rxns["PWY-2681"])]
# RXN-4308             {}
# RXN-4305    {2.5.1.112}
# RXN-4317             {}
# RXN-4310             {}
# RXN-4306             {}
# RXN-4314             {}
# RXN-4303    {2.5.1.112}
# RXN-4307     {2.5.1.27}
# RXN-4313             {}
# RXN-4312             {}
# RXN-4304             {}

The following to confirm:

grep "RXN-4308" metacyc_reactions_level4ec_only.uniref

Are there supposed to be ECs associated with some of the rxns here since it's in the pathway?

[GenoMax]

Those two entry appear to be dismutases and that word seems to refer to many reactions:https://en.wikipedia.org/wiki/Disproportionation

[O.rka]

That would make a lot of sense. In that instance, I'm less concerned because after a closer look I realized that's only the case for 4 UniRef50 ids and it's the same 2 EC for all 4. Do you have any insight on teethe rxns missing ECs by any chance?