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beta amyloid formation is_a relationship #11018

Closed gocentral closed 9 years ago

gocentral commented 10 years ago

Hi,

I would like to make a relationship modification to existing terms:

I want to create an 'is_a' relationship between child term: beta-amyloid formation (GO:0034205) to the parent term: amyloid fibril formation (GO:1990000).

Evidence: PMID:19158505 (file attached) :

My reasoning for this relationship is: There is no relationship between beta-amyloid formation (GO:0034205) and amyloid fibril formation (GO:1990000). Beta sheet structure is common in all amyloid fibrils. However the formation of the amyloid fibrils differ by the precursor protein (Table 1 from PMID:19158505). In the GO term, amyloid fibril formation (GO:1990000), the definition does not state the precursor protein. However in the GO term, beta-amyloid formation (GO:0034205), the precursor protein (APP) is stated in the definition. Therefore we can create an 'is_a' relationship between child term beta-amyloid formation (GO:0034205) to the parent term amyloid fibril formation (GO:1990000), since beta-amyloid formation is a subtype of amyloid fibril formation.

Thank you, Sejal

Reported by: sejal-24

Original Ticket: geneontology/ontology-requests/10833

gocentral commented 10 years ago

Original comment by: paolaroncaglia

gocentral commented 10 years ago

Hi Sejal,

I'm afraid the two terms refer to different processes while both using the same string 'formation'.

beta-amyloid formation = The generation of beta-amyloid by cleavage of the amyloid precursor protein (APP). where beta-amyloid = polypeptide So gene products annotated to 'beta-amyloid formation' would be e.g. secretases involved in cleaving the APP to form A-beta. The term really means 'beta-amyloid biosynthetic process from amyloid precursor protein (APP)'. Its parents, in fact, are 'amyloid precursor protein catabolic process' and 'beta-amyloid metabolic process'. On the other hand,

amyloid fibril formation = The generation of amyloid fibrils, insoluble fibrous protein aggregates exhibiting beta sheet structure, from proteins. An example of this is seen when human RIP1 and RIP3 kinases form a heterodimeric functional amyloid signaling complex (PMID:22817896). Its parents are 'fibril organization' and 'protein metabolic process'. As your attached paper notes, fibril formation is likely to be a "nucleation dependent polymerisation ... likening the process to crystallization". So gene products involved in 'amyloid fibril formation' are the amyloid proteins themselves - plus possibly other factors that aid the process - but to my knowledge secretases are not directly involved. If I made 'beta-amyloid formation' is_a 'amyloid fibril formation', secretases would be annotated to 'amyloid fibril formation' which is very likely false.

I can see why you'd want to link the two terms, but I think the confusion here is because what the paper refers to in Table 1 is 'beta-amyloid FIBRIL formation' rather than 'beta-amyloid formation'. If we created a new term for 'beta-amyloid fibril formation', what would you annotate to it other than beta-amyloid? I could still create the term of course, and that would be is_a 'amyloid fibril formation'.

Given the meaning of the two terms, links such as beta-amyloid formation part_of amyloid fibril formation or amyloid fibril formation has_part beta-amyloid formation would be incorrect. If we created 'beta-amyloid fibril formation', this process would depend critically on the generation (formation, biosynthesis) of beta-amyloid from APP, in that beta-amyloid is not found as such in nature, I seem to remember :-) If so, i.e. if 'beta-amyloid fibril formation' can't occur without formation of A-beta from APP, then we could have 'beta-amyloid fibril formation' has_part 'beta-amyloid formation' (annotations don't propagate over has_part, so we wouldn't create violations).

To hopefully clear the naming confusion, I'd add exact synonyms 'beta-amyloid biosynthetic process from amyloid precursor protein' and 'beta-amyloid biosynthetic process from APP' to 'beta-amyloid formation'

All this prompted me to look at manual annotations to 'beta-amyloid formation'. Several look a bit misplaced, at a quick glance. These are yours Sejal:

CLU (clusterin): "Clusterin promotes amyloid plaque formation" from the paper title... please check PICALM (Phosphatidylinositol-binding clathrin assembly protein) (3 annotations): "Decreased CALM expression reduces Aβ42 to total Aβ ratio through clathrin-mediated endocytosis of γ-secretase" is the paper title. 'regulation of beta-amyloid formation'?

The others are from other databases, I'll check with them: GSAP (gamma secretase activating protein): judging by the name, presumably 'positive regulation of beta-amyloid formation'? TMED10 (a transmembrane protein): judging from paper title, 'regulation of beta-amyloid formation'? PSEN1 (presenilin1): should be ok (gamma-secretase is a protein complex made of presenilin (PS), nicastrin (NCT), Pen2, and Aph1) FKBP1A (Peptidyl-prolyl cis-trans isomerase FKBP1A) "differentially accelerates fibril formation of wild type alpha-synuclein" from the paper title... sounds like the annotation should go to a true 'fibril formation' term but curators should check the full text please CLU (clusterin): "Clusterin promotes amyloid plaque formation" from the paper title... please check

OK sorry for the long response, let me know what you think. Thanks, Paola

Original comment by: paolaroncaglia

gocentral commented 10 years ago

Hi Paola,

You are absolutely correct about the difference between beta-amyloid formation and amyloid fibril formation. (I should have thought about this more in detail before requesting the change). I don't think there is a need for me to create new terms such as 'beta-amyloid fibril formation'. When I was double checking the annotations I made to 'beta-amyloid formation', I realized that they should have been annotated to the regulation term instead. I made the changes, and I feel that 'regulation of beta-amyloid formation' (or its child positive/negative) works best for representing the experimental data.

Thanks, Sejal

On Wed, May 7, 2014 at 4:28 PM, Paola Roncaglia <paolaroncaglia@users.sf.net

wrote:

Hi Sejal,

I'm afraid the two terms refer to different processes while both using the same string 'formation'.

beta-amyloid formation = The generation of beta-amyloid by cleavage of the amyloid precursor protein (APP). where beta-amyloid = polypeptide So gene products annotated to 'beta-amyloid formation' would be e.g. secretases involved in cleaving the APP to form A-beta. The term really means 'beta-amyloid biosynthetic process from amyloid precursor protein (APP)'. Its parents, in fact, are 'amyloid precursor protein catabolic process' and 'beta-amyloid metabolic process'. On the other hand,

amyloid fibril formation = The generation of amyloid fibrils, insoluble fibrous protein aggregates exhibiting beta sheet structure, from proteins. An example of this is seen when human RIP1 and RIP3 kinases form a heterodimeric functional amyloid signaling complex (PMID:22817896). Its parents are 'fibril organization' and 'protein metabolic process'. As your attached paper notes, fibril formation is likely to be a "nucleation dependent polymerisation ... likening the process to crystallization". So gene products involved in 'amyloid fibril formation' are the amyloid proteins themselves - plus possibly other factors that aid the process - but to my knowledge secretases are not directly involved. If I made 'beta-amyloid formation' is_a 'amyloid fibril formation', secretases would be annotated to 'amyloid fibril formation' which is very likely false.

I can see why you'd want to link the two terms, but I think the confusion here is because what the paper refers to in Table 1 is 'beta-amyloid FIBRIL formation' rather than 'beta-amyloid formation'. If we created a new term for 'beta-amyloid fibril formation', what would you annotate to it other than beta-amyloid? I could still create the term of course, and that would be is_a 'amyloid fibril formation'.

Given the meaning of the two terms, links such as beta-amyloid formation part_of amyloid fibril formation or amyloid fibril formation has_part beta-amyloid formation would be incorrect. If we created 'beta-amyloid fibril formation', this process would depend critically on the generation (formation, biosynthesis) of beta-amyloid from APP, in that beta-amyloid is not found as such in nature, I seem to remember :-) If so, i.e. if 'beta-amyloid fibril formation' can't occur without formation of A-beta from APP, then we could have 'beta-amyloid fibril formation' has_part 'beta-amyloid formation' (annotations don't propagate over has_part, so we wouldn't create violations).

To hopefully clear the naming confusion, I'd add exact synonyms 'beta-amyloid biosynthetic process from amyloid precursor protein' and 'beta-amyloid biosynthetic process from APP' to 'beta-amyloid formation'

All this prompted me to look at manual annotations to 'beta-amyloid formation'. Several look a bit misplaced, at a quick glance. These are yours Sejal:

CLU (clusterin): "Clusterin promotes amyloid plaque formation" from the paper title... please check PICALM (Phosphatidylinositol-binding clathrin assembly protein) (3 annotations): "Decreased CALM expression reduces Aβ42 to total Aβ ratio through clathrin-mediated endocytosis of γ-secretase" is the paper title. 'regulation of beta-amyloid formation'?

The others are from other databases, I'll check with them: GSAP (gamma secretase activating protein): judging by the name, presumably 'positive regulation of beta-amyloid formation'? TMED10 (a transmembrane protein): judging from paper title, 'regulation of beta-amyloid formation'? PSEN1 (presenilin1): should be ok (gamma-secretase is a protein complex made of presenilin (PS), nicastrin (NCT), Pen2, and Aph1) FKBP1A (Peptidyl-prolyl cis-trans isomerase FKBP1A) "differentially accelerates fibril formation of wild type alpha-synuclein" from the paper title... sounds like the annotation should go to a true 'fibril formation' term but curators should check the full text please CLU (clusterin): "Clusterin promotes amyloid plaque formation" from the paper title... please check

OK sorry for the long response, let me know what you think. Thanks,

Paola

Status: open Group: None

Labels: Other term-related request neurobiology Created: Wed May 07, 2014 11:17 AM UTC by Sejal Last Updated: Wed May 07, 2014 02:01 PM UTC Owner: Paola Roncaglia

Hi,

I would like to make a relationship modification to existing terms:

I want to create an 'is_a' relationship between child term: beta-amyloid formation (GO:0034205) to the parent term: amyloid fibril formation (GO:1990000).

Evidence: PMID:19158505 (file attached) :

My reasoning for this relationship is: There is no relationship between beta-amyloid formation (GO:0034205) and amyloid fibril formation (GO:1990000). Beta sheet structure is common in all amyloid fibrils. However the formation of the amyloid fibrils differ by the precursor protein (Table 1 from PMID:19158505). In the GO term, amyloid fibril formation (GO:1990000), the definition does not state the precursor protein. However in the GO term, beta-amyloid formation (GO:0034205), the precursor protein (APP) is stated in the definition. Therefore we can create an 'is_a' relationship between child term beta-amyloid formation (GO:0034205) to the parent term amyloid fibril formation (GO:1990000), since beta-amyloid formation is a subtype of amyloid fibril formation.

Thank you,

Sejal

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Original comment by: sejal-24

gocentral commented 10 years ago

Hi Sejal,

Thanks. Also, going back to my suggestion of adding a link 'beta-amyloid fibril formation' has_part 'beta-amyloid formation', this would probably be over-stretching it anyway. 'beta-amyloid formation' happens before 'beta-amyloid fibril formation', but I'm not 100% sure that 'beta-amyloid fibril formation' occurs every time a beta-amyloid is cleaved from APP. Anyway, not needed now.

To lift the 'formation' confusion, I added these exact synonyms to 'beta-amyloid formation': beta-amyloid polypeptide formation from amyloid precursor protein beta-amyloid polypeptide formation from APP

I also extended the definition comment to 'beta-amyloid formation' to include: This term refers to the production of the beta-amyloid polypeptide from the amyloid precursor protein (APP), and should be used to annotate e.g. secretases that cleave APP to form beta-amyloid. To annotate gene products involved in the formation of amyloid fibrils, please consider 'amyloid fibril formation' (GO:1990000).

Thanks for rehousing your annotations. I'll follow-up separately with the other databases that have direct manual annotations to 'beta-amyloid formation'.

Paola

Original comment by: paolaroncaglia

gocentral commented 10 years ago

For my reference, the annotation SF ticket is: https://sourceforge.net/p/geneontology/annotation-issues/1168/

Closing this ontology ticket now.

Paola

Original comment by: paolaroncaglia

gocentral commented 10 years ago

Original comment by: paolaroncaglia

gocentral commented 10 years ago

But this discussion opens a different problem. Beta-amyloid formation (GO:0034205) points to a single protein: note the pointer to P05067 in the wikipedia entry http://en.wikipedia.org/wiki/Beta_amyloid. But GO does not annotate single proteins (or ortholog families)?

Original comment by: deustp01

gocentral commented 10 years ago

Original comment by: paolaroncaglia

gocentral commented 10 years ago

Hi Peter,

An entry for beta-amyloid (meant as a class of peptides, not just a single one; the wikipedia entry points also to PFAM PF03494, http://pfam.xfam.org/family/PF03494) was requested to ChEBI a couple of years ago (by Becky), and accepted; the peptides range from 36 to 43 amino acids (ChEBI has a cut-off of 50 aa). So we deemed relevant GO terms in scope for GO. This is analogous to the case of insulin terms in GO (insulin is 51 aa, but ChEBI took it in). Also, this class of peptides is very relevant for fibril formation, and for the Alzheimer's Disease Annotation Project (http://wiki.geneontology.org/index.php/Alzheimer%27s_Disease_Annotation_Project). I hope this makes sense.

Thanks, Paola

Original comment by: paolaroncaglia

gocentral commented 10 years ago

Original comment by: paolaroncaglia

gocentral commented 10 years ago

Hi again Peter,

In addition to my previous comment, I wished to add that I discussed this with Jane too. Sure we don't routinely want terms in GO that refer to specific proteins (but we're ok with classes of peptides/proteins), but OTOH, there are cases such as some viral processes where specific proteins are really relevant for those processes and we need to be able to represent that in GO. I hope this clarifies the matter. Also, we'll briefly present the Alzheimer's GO project at the annotation call today if we have time (if not, at the next one).

I'm going to close this ticket now, but feel free to comment.

Thanks, Paola.

Original comment by: paolaroncaglia

gocentral commented 10 years ago

Original comment by: paolaroncaglia

gocentral commented 10 years ago

Sure - the term does indeed point to a family so it works for me too.

Original comment by: deustp01