Can expand MP terms to Fungi?

[zhengj2007]

VEuPathDB (http://veupathdb.org) need following terms for Fungi phenotype annotation:

• hypoxia
• oxidative stress

We found the terms in MP and they are asserted under 'mammalian phenotype' in UPHENO. Hypoxia http://purl.obolibrary.org/obo/MP_0005039 Definition: Reduced oxygenation of body tissues resulting in the decreased pressure of this component of body gases; commonly due to hypoxemia [database_cross_reference: ISBN:978-0-387-75246-4]

oxidative stress http://purl.obolibrary.org/obo/MP_0003674 Definition: Condition characterized by an accumulation of free radical groups in the body, which creates a potentially unstable and damaging cellular environment linked to tissue damage, accelerated aging, and degenerative disease; can result from many factors, including exposure to alcohol, medications, poor nutrition, trauma, cold or toxins; may be indicated by low antioxidant levels measured in blood plasma [database_cross_reference: MESH:G06.535.710]

Is it possible to make the terms more general and we can use it to annotate Fungi phenotype?

Thanks!

[sbello]

I think the hypoxia term could be created using the abnormallyDecreasedLevelOfChemicalEntity.yaml pattern. That matches the EQ of the MP term.

Oxidative stress is a bit trickier. There is a term for radical in CHEBI but free radical is just a related synonym so I'm not sure if this would be the correct term to use. If we can find free radical in an ontology or if radical is acceptable I think we could use the abnormallyIncreasedLevelOfChemicalEntity.yaml pattern for oxidative stress.

[pnrobinson]

Is "Oxidative stress" really a phenotype or is it an inference about the likely pathophysiology?

[sbello]

I think the MP definition has a bit too much about the possible causes of oxidative stress but the core part 'accumulation of free radical groups in the body' seems to me to be a valid phenotype. Multiple sources refer to oxidative stress as:

Oxidative stress arises when the production of reactive oxygen species overwhelms the intrinsic anti-oxidant defenses - https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3101336/

Oxidative stress is a phenomenon caused by an imbalance between production and accumulation of oxygen reactive species (ROS) in cells and tissues and the ability of a biological system to detoxify these reactive products. - https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5551541/

Oxidative stress is defined as an imbalance between the production of free radicals and the antioxidant system, which is in charge of keeping the homeostasis of the organism (Betteridge, 2000). - https://www.sciencedirect.com/topics/neuroscience/oxidative-stress

Based on these we may want to capture the more about the imbalance, but since the end product of this is accumulation of reactive oxygen species I think the increased level pattern is not incorrect.

[zhengj2007]

@pnrobinson @sbello Thanks for your discussion. Is it possible that we use hypoxia and oxidative stress for Fungi phenotype annotation? Thanks!

[sbello]

I wouldn't want you to use the actual MP terms as the ontology is for mammals but creating new terms using the UPheno patterns seems fine to me. @matentzn any suggestions?

[zhengj2007]

@sbello We don't want to use MP terms. It sounds good to us that UPheno can add 'hypoxia' and 'oxidative stress'. Thanks!

[dosumis]

GO has some potentially relevant terms: https://www.ebi.ac.uk/ols/ontologies/go/terms?iri=http%3A%2F%2Fpurl.obolibrary.org%2Fobo%2FGO_0006979

[Achchuthan]

Hi @dosumis,

I work with @zhengj2007 at VEuPathDB. The relevant GO terms "response to hypoxia" and "response to oxidative stress" describes the biological processes that occurs in response to the change in conditions such as hypoxia and oxidative stress.

For the curation of phenotypes, the terms from MP were more appealing to me. They would make more sense when we use an Entity + Quality approach where "hypoxia" and "oxidative stress" are used as entity and combined with quality terms such as "resistant to" or "sensitive to". Therefore, we were wondering whether it would be possible to create new terms in UPheno that could be used across taxons without any restrictions?

Thanks a lot for your help.

Best wishes, Achchuthan

[sbello]

Discussed in upheno call, we think this should be done. @matentzn how do we make this happen?

[matentzn]

@Achchuthan we plan to make it happen, but it will take a while to set this up (once the infrastructure is there, it will be easy to add new terms). Could you tell me a bit what your deadlines and urgency levels on this is?

[Achchuthan]

Hi @matentzn, Thanks a lot for agreeing to add new terms. I am currently using terms from non-OBO foundry ontologies. Ideally, we would like to use terms from OBO Foundry ontologies only and having these terms in UPheno will be great. But, it is not urgent.

Thanks, Achchuthan

[matentzn]

Sounds good! Thank you!

[matentzn]

@sbello

for these terms, would this be appropriate:

hypoxia: decreasedLevelOfChemicalEntity, CHEBI:oxygen atom? see http://purl.obolibrary.org/obo/MP_0005039

secondly, what about (abnormal) oxidative stress? is it a phenotype? if so, what pattern?

[cmungall]

Sorry, just noticed this ticket for the first time

oxidative stress and hypoxia are not phenotypes

Do we not have these in ECTO?

[diatomsRcool]

I think oxidative stress and hypoxia could be a characteristic of an environment or an organism. One could be exposed to oxidative stress or be exposed to hypoxia. One could also look at an organism and see that it is exhibiting signs of oxidative stress or hypoxia. Whether or not it is appropriate to say that oxidative stress and hypoxia in an organism is a phenotype ..... I'm not sure. These can both be added to ECTO as exposure to oxidative stress and exposure to hypoxia. They would likely be composed from ENVO terms.

[sbello]

@cmungall Why do you believe hypoxia and oxidative stress are not phenotypes? Both terms exist in the MP and Peter and I had some back and forth earlier in the ticket as to whether or not these are phenotypes. We also discussed this on the upheno call and decided it would be appropriate to use these as phenotypes. We aren't talking about a hypoxic environment but hypoxia within the organism that may or may not have anything to do with the external environment. Definitions of oxidative stress are in an earlier comment on this thread. Or are you objecting to the labels?

[matentzn]

According to Wikipedia, Hypoxia seems a (very ugly looking) phenotype, and at least some sources say similar things for oxidative stress.

@Achchuthan before we get int the trenches of our debate here on the nature of oxidative stress and hypoxia, may I ask: are you seeking to annotate "increased/decreased sensitivity to oxidative stress in the environment" (increased sensitivity to environmental exposure) / "increased resistance to lack of oxygen", or are you looking to say: "increased imbalance between free radicals and antioxidants in your body" (oxidative stress)?

[cmungall]

OK, retracting objections for now, will try and write more later...

[pnrobinson]

@sbello Hypoxemia is defined as a decrease in the partial pressure of oxygen in the blood whereas hypoxia is defined by reduced level of tissue oxygenation. -- In clinical situations, at least, it is routine to measure Hypoxemia. -- People often speak of hypoxia, but it is an inference based on direct measurements of hypoxemia and some organ dysfunction. I think Hypoxia is valid although in clinical situations it is not what is actually measured. --Oxidative stress is an inference. It is possible to measure specific manifestations of oxidative stress (https://www.epigentek.com/catalog/epiquik-ohdg-dna-damage-quantification-direct-kit-colorimetric-p-2930.html?utm_source=google&utm_medium=cpc&utm_campaign=Kits-%208-OHdg_Oxidative-DNA-Damage-Stress&gclid=CjwKCAiA7939BRBMEiwA-hX5JzdzB2OiyNhE4ymMpUaF3bp0gHDS0Q8Fb0krmtfUyILdWltuzXkiMxoCthEQAvD_BwE) and many others. I do not think that the implications of positivity in all of the many assays related to oxidative stress are equivalent. Therefore, if people annotate to a term "oxidative stress", we loose information. Many of the assays also do not ONLY measure oxidative stress, and so if we tried to model this, it would lead to a polyhierarchy.

[sbello]

Thanks @pnrobinson I've created a ticket for the MP to review the annotations to this term. Part of the issue is that in annotating we are often dealing with conclusions presented by the authors that don't provide the full details. That said, a casual review of the annotations in MGI to the oxidative stress term revealed a number of questionable annotations.

[srengel]

in the APO, we use the term 'oxidative stress resistance' with qualifiers as appropriate (decreased, increased, etc.).

[sbello]

@pnrobinson We have both hypoxia and hypoxemia terms. I've created an MP ticket to review these as well. But here we have more direct tissue and cell measures of hypoxia. Although many are capturing cases where the mice fail to breath after birth.

@srengel In most of the MGI uses of oxidative stress we are capturing cases where the mice display elevated levels of markers of oxidative stress without an exeternal intervention to create the stress so I would not want to use 'oxidative stress resistance'. Although some of the incorrect uses I've come across may be more appropriately annotated to that term.

[Achchuthan]

Hi @matentzn, Sorry for the delayed reply. I am looking to annotate "increased/decreased sensitivity to oxidative stress in the environment" (increased sensitivity to environmental exposure) / "increased/ decreased resistance to lack of oxygen".

Thanks, Achchuthan

[sbello]

@Achchuthan for that annotation I would not want to use the MP meaning of hypoxia or oxidative stress which are referring to the phenotype in the organism. Instead I would use the GO terms 'cellular response to hypoxia' or 'cellular response to oxidative stress' in either the 'Abnormally decreased quality of biological process' (http://purl.obolibrary.org/obo/upheno/patterns-dev/abnormallyDecreasedQualityOfBiologicalProcess.yaml) or in a new pattern we will need to make to capture Abnormally increased quality of biological process.

@matentzn We will need to create an 'Abnormally increased quality of biological process' should be simple enough we just need to swap in increased process quality (PATO:0002304) for decreased process quality and make a few text changes.

[matentzn]

Awesome, thank you @sbello - thats super helpful!

It still does my head in when to use: "increased sensitivity to" some environmental exposure vs decreased "response to biological process" - But yea, since we decided to use GO-based modelling whenever in doubt, I guess that's the right way to go here.

[mah11]

ty to" some environmental exposure vs decreased "response to biological process"

I can't speak for anyone or anything else, but this is what we do with FYPO: We have both flavors in the ontology, and make the call at the annotation level. For experiments that only look at cell population survival and growth (which are the vast majority, actually), we use "sensitivity to x". If they've looked more specifically at a response (e.g. assay a signaling pathway or effect at the molecular level), we use a "response to x" term. This doesn't eliminate all grey areas but it's a decent guideline that works pretty well for microorganisms that grow in cultures on plates or in flasks.

Belatedly, @Achchuthan would it be at all useful to look at FYPO terms? For example, we have a few terms classified under 'abnormal cellular response to oxidative stress' (FYPO:0000180) ... FYPO doesn't have anything multicellular but for anything cell-level it might help.

[sbello]

@mah11 Do we have a Upheno pattern for both flavors? The decreased quality of a biological process was the only one I found. Did I miss the other or do we need to add this?

[mah11]

Hmmm, FYPO uses a placeholder pattern that basically says the process of vegetative growth has increased sensivitity towards a substance, e.g. (FYPO:0000088 sensitive to hydroxyurea):

'has part' some 
    ('increased sensitivity of a process'
     and ('inheres in' some 'single-celled organism vegetative growth phase')
     and (towards some hydroxyurea))

Similarly, FYPO chemical resistance phenotypes use 'decreased sensivitity of a process' and the same growth term from GO.

I don't know the current status of a upheno equivalent for either ... @matentzn do you?