Fix Various Issues with Lipoic Acid Biosynthesis

[Devlin-Moyer]

Main improvements in this PR:

As proposed in #685:

• Creates MAM02643m to represent mitochondrial octanoyl-ACP
• Creates MAM02042m to represent mitochondrial HS^-
• Creates MAM01098m to represent mitochondrial 5’-deoxyadenosine
• Creates MAM20084m to represent a mitochondrial 4Fe4S iron-sulfur cluster
• Creates MAM20085m to represent a mitochondrial 2Fe2S iron-sulfur cluster
• Creates MAM20086m to represent mitochondrial GSSH
• Adds all of these genes to Human-GEM:
  • ENSG00000100209, HSCB
  • ENSG00000105755, ETHE1
  • ENSG00000109519, GRPEL1
  • ENSG00000113013, HSPA9
  • ENSG00000135070, ISCA1
  • ENSG00000136003, ISCU2
  • ENSG00000137714, FDX1
  • ENSG00000137767, SQOR
  • ENSG00000165898, ISCA2
  • ENSG00000169599, NFU1
  • ENSG00000181873, IBA57
  • ENSG00000182512, GLRX5
  • ENSG00000214113, LRYM4
  • ENSG00000244005, NFS1
  • ENSG00000267673, FDX2
• Replaces MAM00210c with MAM00210m, MAM00209c with MAM00209m, and MAM00208c with MAM00208m in all of the reactions they participate in
• Replaces all cytosolic metabolites in MAR06404 with their mitochondrial equivalents
• Adds ENSG00000137767 to the GPR of MAR06911
• Changes MAR06402 to MAM02643m -> MAM00210m + MAM02484m, GPR: ENSG00000004779 and ENSG00000140905 and ENSG00000175536, references: PMID:24777537;PMID:28757203
• Changes MAR06403 to MAM00210m + 3 MAM02039m + MAM02555m + 2 MAM02877m + MAM20084m --> MAM00208m + 2 MAM01098m + 4 MAM01821m + 2 MAM02042m + 2 MAM02471m + MAM02554m
  • GPR: (ENSG00000121897 and ENSG00000137714 and ENSG00000140905 and ENSG00000161513 and ENSG00000135070 ) or (ENSG00000121897 and ENSG00000137714 and ENSG00000140905 and ENSG00000161513 and ENSG00000165898) or (ENSG00000121897 and ENSG00000137714 and ENSG00000140905 and ENSG00000161513 and ENSG00000169599)
  • references: PMID:24777537;PMID:31493409;PMID:36281303;PMID:37453661
• Creates MAR20184 to represent synthesis of 4Fe4S iron-sulfur clusters in mitochondria:
  • 2 MAM01371m + 2 MAM02040m + MAM02555m + 2 MAM20085m -> 2 MAM01285m + 3 MAM02039m + MAM02554m + 2 MAM02751m + MAM20084m
  • GPR: ENSG00000100209 and ENSG00000109519 and ENSG00000113013 and ENSG00000135070 and ENSG00000161513 and ENSG00000165898 and ENSG00000181873 and ENSG00000182512 and ENSG00000267673
  • references: PMID:31918395;PMID:31935115
• Creates MAR20185 to represent synthesis of 2Fe2S iron-sulfur clusters in mitochondria:
  • 2 MAM01628m + 2 MAM01821m + MAM02555m -> 2 MAM01307m + MAM02039m + MAM02554m + MAM20085m
  • GPR: ENSG00000004779 and ENSG00000136003 and ENSG00000161513 and ENSG00000165060 and ENSG00000214113 and ENSG00000244005 and ENSG00000267673
  • references: PMID:31918395;PMID:31935115
• Creates MAR20186 to represent the formation of GSSH from GSH and HS^- by SQOR:
  • MAM01802m + MAM02026m + MAM02039m + MAM02042m -> MAM01803m + MAM20086m
  • GPR: ENSG00000137767
  • references: PMID:25225291
  • E.C.: 1.8.5.8, KEGG: R11929, RHEA:62608
• Creates MAR20187 to represent the conversion of GSSH into GSH and sulfite by ETHE1:
  • MAM02040m + MAM02630m + MAM20086m -> MAM02026m + 2 MAM02039m + MAM02949m
  • GPR: ENSG00000105755
  • references: PMID:25225291
  • E.C.: 1.13.11.18, KEGG: R08678, RHEA:12981
• Creates MAR20188: MAM01098m -> MAM01098c, references: PMID:34126623 (no GPR)
• Removes ENSG00000092529 and ENSG00000181652 from genes.tsv to fix the YAML validation error that was introduced after they were removed from Human-GEM.yml but not genes.tsv in Fix: GPR curation for starch and sucrose metabolism #933 and Fix: GPR curation for subsystems related with amino acid #936

I hereby confirm that I have:

• Tested my code on my own computer for running the model
• Selected develop as a target branch
• Any removed reactions and metabolites have been moved to the corresponding deprecated identifier lists

[Devlin-Moyer]

hmm I'm not seeing whatever YAML formatting issue the tests are apparently finding (although it's weird that the "YAML validation" tests passed but the "Test YAML conversion" ones failed; I feel like they usually either both work or both fail, but I'm not sure what the differences between them are)

[feiranl]

Thanks! will start to review when the new release is published.

[Devlin-Moyer]

The YAML validation error appears to be caused by ENSG00000181652 and ENSG00000092529 being in genes.tsv but not Human-GEM.yml; neither gene was affected by this pull request, and I see that a large number of pull requests were recently merged, so I haven't bothered to look through them to figure out exactly where/when this happened

[edkerk]

As a tip, you can often quickly find out when specific genes (or other objects) are mentioned in previous issues or PRs, like for ENSG00000181652.

But yes, both genes should be removed from genes.tsv, , as mentioned here and here.

[JHL-452b]

While running the check tasks locally, I noticed that errors are still being reported. I'm wondering if you directly integrated the gene.tsv file from the develop branch? There are still some issues present in the develop branch, as I described in issue #938 .

[Devlin-Moyer]

yea when I was merging in the latest version of the develop branch, I saw that there was a merge conflict for all rows except the first row in genes.tsv and wasn't sure why. I just used the version from the develop branch since I figured there was some reason for large-scale changes like that, and I knew that most of the recently merged PRs were specifically about curating GPRs.

[edkerk]

It is resolved now. Seems like @JHL-452b approved it earlier already, so I will merge it.

[github-actions]

This PR has been automatically tested with GH Actions. Here is the output of the gene essentiality test:

     cellLine     TP     TN     FP     FN     accuracy    sensitivity    specificity       F1         MCC   
    __________    __    ____    ___    ___    ________    ___________    ___________    ________    ________

    {'DLD1'  }    50    2147     85    272    0.86022       0.15528        0.96192       0.21882     0.17386
    {'GBM'   }    57    2138     78    280    0.85977       0.16914         0.9648       0.24153     0.20259
    {'HCT116'}    71    2179     70    289     0.8624       0.19722        0.96888       0.28343     0.25335
    {'HELA'  }    35    2219    106    251    0.86327       0.12238        0.95441       0.16393      0.1061
    {'RPE1'  }    21    2163    114    255    0.85546      0.076087        0.94993       0.10219    0.036105
    {'all'   }     8    2357    133    113    0.90578      0.066116        0.94659      0.061069    0.011814

Note: In the case of multiple test runs, this post will be edited.