[Ontology-editors] small molecule metabolism

Valerie Wood val at sanger.ac.uk
Tue Apr 14 04:04:49 PDT 2009 

Do we need to include these di-polymers in the small molecule pathways?  
if not,  it  could be defined as non-polymeric molecules as Harold 
suggested?

There do not appear to be many metabolic pathways which involve the 
disaccharides which do not involve their catabolism into their component 
mono-saccharides, or their attachment to a macromolecule?
 in which case I don't think we would lose anything be defining

"small molecule metabolism, or metabolite metabolism"  as

The chemical reactions and pathways, including anabolism and catabolism, 
by which living organisms transform non-polymeric organic molecules.

and groupling all of small molecule metabolism under here ( excluding 
disaccharide metabolic process)

a di-polymer is therefore neither a small molecule of a macromolecule by 
current def (the macromolecule def is actually vaguer because it refers 
to "high" relative molecular mass....)

Val


Harold Drabkin wrote:

> arrgh! Alex reminded me of sucrose and lactose.
> maybe we want to cut it off above 2?
>
> There goes my epiphany!
>
> h
>
>
> Harold Drabkin wrote:
>
>> a thought..
>>
>> How about saying that these are the non-polymeric molecules found 
>> within a cell? (assuming we do not want to count di-peptides, 
>> di-nucleotides, or di-saccharides )?
>>
>> hd
>>
>> Chris Mungall wrote:
>>
>>>
>>> On Apr 9, 2009, at 9:35 AM, Valerie Wood wrote:
>>>
>>>> Tanya Berardini wrote:
>>>>
>>>>>
>>>>>
>>>>> On Thu, Apr 9, 2009 at 8:48 AM, Chris Mungall <cjm at berkeleybop.org 
>>>>> <mailto:cjm at berkeleybop.org>> wrote:
>>>>>
>>>>>
>>>>>    On Apr 9, 2009, at 3:35 AM, Valerie Wood wrote:
>>>>>
>>>>>        It seems like there is a gap in the terminology of biology to
>>>>>        decribe "everything that is not a macromolecule molecule".
>>>>>        Maybe we should make one up....
>>>>>        Perhaps "small molecule metabolism" would be acceptable if it
>>>>>        is defined as "everything that is not a macromolucule" but
>>>>>        that is not an acceptable way of defining something is it?
>>>>>
>>>>>
>>>>>    Do we really need a term for it? Why not just ask for non-X
>>>>>    metabolism any time you're interested in metabolism of Ys where Ys
>>>>>    are not Xs
>>>>>
>>>>>    Granted tools can't do this yet but it's not hard given the
>>>>>    correct structures in the ontology, and we should perhaps be
>>>>>    working towards a situation where tools do support this
>>>>>
>>>>>
>>>>> I am partial to this approach.  Defining 'small molecule 
>>>>> metabolism' as everything that is not 'macromolecule metabolism' 
>>>>> violates the ontology design principle of positivity.  Why not 
>>>>> just combine the annotations from the terms that do cover what is 
>>>>> desired and then analyze those results?
>>>>>
>>>>> Tanya
>>>>>
>>>>
>>>> Its quite difficult  to do this during enrichment analysis.
>>>> I have seen  a number of times that   terms which would be 
>>>> classically termed "biochemical pathways" are enriched, bacause I 
>>>> see the annotations  in my data individually.
>>>> The enrichment tools don't show this  because the number of 
>>>> annotations to the individual  terms are not large enough. tThe 
>>>> parent term "cellular metabolic process" is not enriched because 
>>>> the effect is masked  by all of the other 3000 annotations to this 
>>>> term generated  mainly by the variouse types of macromolecule 
>>>> metabolic process i.e.DNA metabolic process, protein metabolic 
>>>> process etc.
>>>>
>>>> When you are analysisng whole genome datasets it isn't really 
>>>> practical to add and subtract processes and repeat enrichment (it 
>>>> gets way too complicated to process and report the results, as you 
>>>> would have to fiddle with the P-values for everything you did 
>>>> manually and then reintegrate it into your whole genome analysis)
>>>>
>>>> This isn't really a problem for me now because I worked around it, 
>>>> but I could only do this because I know what the problem was.
>>>>
>>>> I thought that other users may appreciate some sort of grouping 
>>>> term here for similar analyses- it just seems that there should be 
>>>> a term to group these processes in the same way that macromolecular 
>>>> metabolic processes are grouped. The fact is that if you have a 
>>>> bunch of genes enriched for low numbers of  various small 
>>>> metabolism/canonical biochemical pathway terms, this  enrichment 
>>>> would  most likely be overlooked.
>>>
>>>
>>> I agree with Tanya but understand the practical need for enrichment 
>>> analysis.
>>>
>>> I am envisioning a partial solution along the following lines:
>>>
>>> Just as we have goslims, we can have gofats. a gofat would live 
>>> outside the ontology and contain statements like
>>>
>>> GOFAT:1 small molecule metabolism = metabolism and not 
>>> has_participant chebi:macromolecule
>>>
>>> The reasoner would compute is_a parentage to the fat terms and 
>>> create a derived obo file. If the tool accepts OBOFs+GAFs then just 
>>> give the tool this obo file instead of the regular one.
>>>
>>> (note this only works for tools that allow you to input an obo file. 
>>> Some web-based tools may not give you the flexibility to substitute 
>>> anything other than the regular GO)
>>>
>>> This should work in your particular case, no need to keep 
>>> re-analyzing once you've defined your fat. We could even make the 
>>> fat-derived obo files available on the website, as we do for slims
>>>
>>> This solution isn't perfect as it requires the analyzer to know a 
>>> priori which may be useful grouping categories. Really the tool 
>>> should be able to do this. For example, for a particular dataset, 
>>> "metabolism with a molecule with an X side chain, missing a Y" may 
>>> be enriched. There are strategies for dealing with this - rule 
>>> mining, or pre-computing every possible cross-product. This will 
>>> require a little more know-how from tools developers.
>>>
>>>
>>>>
>>>> val
>>>>
>>>>
>>>>
>>>>
>>>>
>>>>
>>>>
>>>>
>>>>
>>>> -- 
>>>> The Wellcome Trust Sanger Institute is operated by Genome Research 
>>>> Limited, a charity registered in England with number 1021457 and a 
>>>> company registered in England with number 2742969, whose registered 
>>>> office is 215 Euston Road, London, NW1 2BE.
>>>
>>>
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-- 
 The Wellcome Trust Sanger Institute is operated by Genome Research 
 Limited, a charity registered in England with number 1021457 and a 
 company registered in England with number 2742969, whose registered 
 office is 215 Euston Road, London, NW1 2BE.

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