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SysBioChalmers / Human-GEM

The generic genome-scale metabolic model of Homo sapiens
https://sysbiochalmers.github.io/Human-GEM-guide/
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ARG1 and ARG2 GPRs are incorrect #495

Closed juliette-cooke closed 1 year ago

juliette-cooke commented 1 year ago

I am studying gene knockouts in Human 1, specifically a knockout of the gene ARG1, also known as ENSG00000118520, which codes for ARGN. There is a second gene, ARG2, which codes for a mitochondrial version of the same enzyme (ARGNm).

Current behavior:

Currently in Human 1, knocking out either of the ARG genes has no effect because they are both assigned to the GPR of both ARGN and ARGNm reactions in an "OR". This means that if I knock out ARG1, the ARGN reaction is not affected because ARG2 is still active.

Gene name ENSG Gene card Current single knockout effect
ARG1 ENSG00000118520 ARG1 None
ARG2 ENSG00000081181 ARG2 None

Expected behavior:

Previous models (Recon 2 for example, see below) and the gene cards show that ARG1 codes for ARGN, and ARG2 codes for ARGNm. Therefore, ENSG00000118520 should be the sole gene in the GPR of MAR03816, and ENSG00000081181 should be the sole gene in the GPR of MAR08426. Gene name ENSG Gene card Expected single knockout effect
ARG1 ENSG00000118520 ARG1 MAR03816 (ARGN)
ARG2 ENSG00000081181 ARG2 MAR08426 (ARGNm)

Recon 2

Gene name Gene ID Single knockout effect
ARG1 383.1 ARGN
ARG2 384.1 ARGNm
haowang-bioinfo commented 1 year ago

@juliette-cooke thanks for reporting this!

We are very welcome community contributions that will be incorporated right away after verification.

haowang-bioinfo commented 1 year ago

It is confirmed that arginase-encoding genes ENSG00000118520 and ENSG00000081181 are localised at cytosol and mitochondrion, respectively. The corresponding changes had been made in #496, as proposed.

Please review the changes, and thanks again @juliette-cooke .

haowang-bioinfo commented 1 year ago

Previous models (Recon 2 for example) and the gene cards show that ARG1 codes for ARGN, and ARG2 codes for ARGNm.

By checking Recon3D, it is found that both ARG genes (ENSG00000118520 and ENSG00000081181) are assigned to the GPR of ARGN reaction in an "OR" relation.

haowang-bioinfo commented 1 year ago

@all-contributors please add @juliette-cooke for the bug report.

allcontributors[bot] commented 1 year ago

@haowang-bioinfo

I've put up a pull request to add @juliette-cooke! :tada: