Open Devlin-Moyer opened 1 year ago
Nice Result! Will check this soon. May I know where those protein localizations from? We updated genes.tsv
with the protein localization from HPA (#437) and DeepLoc2(#440) prediction. Is there any conflict localization documentation with what you proposed in this issue?
As briefly mentioned in https://github.com/SysBioChalmers/Human-GEM/issues/607, some mitochondrial reactions in Human-GEM are associated with genes that catalyze analogous reactions in peroxisomes and not mitochondria. I found a total of 128 reactions that involve at least one metabolite in [m] and at least one enzyme known to be involved in fatty-acid oxidation in peroxisomes and not mitochondria:
good work
There are some other issues with some of these reactions, but I'll address those in a different issue so that this one can just be about changing which genes are associated with each.
please do so - it's alway nice to have issues with specific request, while overview discussion is also good
@feiranl I got the localizations from the links in the second table (i.e. Uniprot or various papers when Uniprot did not have a localization or only had a localization "by similarity" or something else that made me suspicious); I did not check genes.tsv/HPA/DeepLoc2, but I can do that
I've edited my recommended new GPRs to align with the localizations given in genes.tsv
from SwissProt/HPA/DeepLoc2 in all cases except:
Current behavior:
As briefly mentioned in #607, some mitochondrial reactions in Human-GEM are associated with genes that catalyze analogous reactions in peroxisomes and not mitochondria. I found a total of 128 reactions that involve at least one metabolite in [m] and at least one enzyme known to be involved in fatty-acid oxidation in peroxisomes and not mitochondria. Trying to address all of them in a single issue proved to be unwieldy, so I've moved most into separate issues, and have edited this one so it only addresses the acyl-CoA dehydrogenation reactions:
MAR01253
ENSG00000072778 or ENSG00000115361 or ENSG00000177646
)MAR01270
ENSG00000072778 or ENSG00000115361 or ENSG00000177646
)MAR03997
ENSG00000072778 or ENSG00000115361
)MAR03291
ENSG00000115361
)MAR03163
ENSG00000122971 or ENSG00000151498 or ENSG00000196177
)MAR03212
ENSG00000122971 or ENSG00000151498 or ENSG00000196177
)Expected behavior:
ACOX1 and ACOX3 catalyze the oxidation of acyl-CoAs into 2-trans-enoyl-CoAs in peroxisomes, so neither of them should be associated with any of these reactions. The enzymes responsible for catalyzing the same reaction in mitochondria are ACADVL, ACADL, ACADM, ACADS, ACADSB, ACAD8, ACAD9, and ACAD11 (see this paper for a general overview of the differences between mitochondrial and peroxisomal beta-oxidation reactions (specifically figure 1)). The ACADs all have different preferences/affinities for acyl-CoAs with different chain lengths, which is why I included a column for the chain length in the above table, and I've tried to ensure my proposed new GPRs reflect these preferences:
Proposed Changes:
MAR01253
andMAR01270
toENSG00000072778 or ENSG00000115361 or ENSG00000177646
MAR03997
toENSG00000072778 or ENSG00000115361
MAR03291
toENSG00000115361
MAR03163
andMAR03212
toENSG00000122971 or ENSG00000151498 or ENSG00000196177