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Change logical definition of 'GO:0019674 NAD metabolic process #23467

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hdrabkin opened this issue Jun 9, 2022 · 8 comments
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Change logical definition of 'GO:0019674 NAD metabolic process #23467

hdrabkin opened this issue Jun 9, 2022 · 8 comments
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@hdrabkin
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hdrabkin commented Jun 9, 2022

Need to change to 'has primary participant some 'NAD(1-)
Will also need to fix children

Do we also need to fix NADH met proc and NADP (change to NADP(-1) as primary and NADPH met proc?

@hdrabkin hdrabkin self-assigned this Jun 9, 2022
@ukemi
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ukemi commented Jun 9, 2022

@deustp01 this came about from my looking at the output of the new cobalamin metabolism model. Because some of the enzymes use NAD and NADH as redox factors, we are inferring that all of the enzymes in the pathway are involved in NAD or NADH metabolism. I think this is misleading, don't you? Certainly there are some pathways that generate or recycle redox potential for cellular use, but wouldn't we want to restrict those manually by declaring the inputs and outputs as primary?

@deustp01
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deustp01 commented Jun 9, 2022

@ukemi agreed - same as not inferring that a MAP kinase cascade is involved in ATP catabolism.

@hdrabkin
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hdrabkin commented Jun 13, 2022

In Quickgo, the following are children of this term

GO:1902690 positive regulation of NAD metabolic process positively_regulates <LD refers to NAD met process; should not need anything once I fix NAD met process

GO:0061722 sulphoglycolysis is_a: has one "has participant' 'NAD(1-); change to primary participant

GO:0019661 glucose catabolic process to lactate via pyruvate is_a NO mention in LD <<<<< not sure

GO:1902689 negative regulation of NAD metabolic process negatively_regulates; refers to NAD met process which will be fixed

GO:0006735 NADH regeneration is_a Both NAD and NADH met processes are inferred. (have to fix NADH met process also.

GO:0006116 NADH oxidation is_a Both NAD and NADH met processes are inferred. (have to fix NADH met process also.

GO:1902688 regulation of NAD metabolic process regulates (LD has NAD met process so should be ok)

@hdrabkin
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Changed NAD and NADP metabolic processes to
'has primary input or output' instead of 'has participant'

@deustp01
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In Quickgo, the following are children of this term

@ukemi I think we do NOT want either GO:0061722 sulphoglycolysis or GO:0019661 glucose catabolic process to lactate via pyruvate as is_a children of GO:0019674. Indeed, either as part of the definition or (better?) as a comment on GO:0019674, we would want o say "This term should not be used to annotate processes in which NAD(H) only provides or consumes reducing equivalents, e.g. sulphoglycolysis or glucose catabolic process to lactate via pyruvate." Will the has_primary_input_labels that Harold just create accomplish this by themselves or are additional changes to the ontology needed. (I guess it's the latter - the new labels may cause a logical inconsistency in the existing structure but not propagate to fix anything?)

And also, if GO:0006116 NADH oxidation and GO:0006735 NADH regeneration are to be child terms (seems OK to me), we also need terms (new or moved from elsewhere) - siblings of these two - for NADH biosynthesis (pretty much everything we've annotated as parts of nicotinate metabolism would fit here) and NADH catabolism, for the synthesis of NADH from other entities and its degradation.

@ukemi
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ukemi commented Jun 16, 2022

As long as @hdrabkin didn't change the logical defs of the other terms, they won't be inferred any more. They will still be participants, but they won't be inferred to be NAD(H) metabolic processes. In order for that inference to be made we have to assert the participation of the NAD(H) as a primary input or output.

@hdrabkin
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Right, I decided to NOT change the child term logical defs.

@deustp01
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And meanwhile, here is a brand new paper from JBC that reviews NAD metabolism (PMID: 35595095) - maybe a good source of expert advice on boundaries between NAD metabolism and NAD turnover in redox reactions.

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