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Re: AD Use Case

From: June Kinoshita <junekino@media.mit.edu>
Date: Tue, 23 Jan 2007 09:49:38 -0500
Message-Id: <01DB38AA-AF6D-4208-8E9E-3619C29A9E14@media.mit.edu>
Cc: Alan Ruttenberg <alanruttenberg@gmail.com>, public-semweb-lifesci <public-semweb-lifesci@w3.org>
To: Tim Clark <twclark@nmr.mgh.harvard.edu>

Sorry for the delayed reply on this. There's now an entry for an ADDL  
antibody in the Alzforum Antibody database. Does that help?

June

On Jan 21, 2007, at 4:33 PM, Tim Clark wrote:

> Well, the point here I'd say is to use the identification of ADDL's  
> in the discourse itself - as the starting point.  Today that would  
> be, you read a paper.  But  I am suggesting we use the SWAN  
> "Research Statement" concerning the role of ADDL's as a jumping off  
> point.
>
> Tim
>
> On SundayJan 21, 2007, at 4:06 PM, Alan Ruttenberg wrote:
>
>>
>> Hi June,
>> The issue wasn't legal use - rather I was trying to point out that  
>> there aren't public databases that include ADDLs that I was aware of.
>> So unlike a gene, which we could identify by a URI based on the  
>> Entrez Gene id, I don't know of an analogous resource to identify  
>> ADDLs. This is probably a job for BioONT - either identify an  
>> existing ontology that includes ADDLs, or generate an ontology  
>> that we could use. In some sense this isn't a technical issue in  
>> using the data for the demo, as much as demonstrating how all of  
>> it places in the larger semantic web.
>>
>> Best,
>> Alan
>>
>>
>>
>> On Jan 21, 2007, at 3:52 PM, June Kinoshita wrote:
>>
>>> I think it would be OK to use the antibody date if we include the  
>>> source/credit tag as agreed upon.
>>>
>>> June
>>>
>>> On Jan 21, 2007, at 9:59 AM, Tim Clark wrote:
>>>
>>>>
>>>> Alan,
>>>>
>>>> DS1 can be provided from SWAN beta which we expect to have out  
>>>> by then.  At minimum we would give the RDF representation from  
>>>> SWAN.  Right June?
>>>>
>>>> Tim
>>>>
>>>> On SundayJan 21, 2007, at 2:33 AM, Alan Ruttenberg wrote:
>>>>
>>>>>
>>>>> I, among others, took the action item to review the AD use case  
>>>>> and associated data sets.  Summary: 7 data sets listed. 2 are  
>>>>> freetext/difficult to convert/query. Wasn't sure how 1 was to  
>>>>> be used. 1 (antibody) has identifier issue for this case. 3  
>>>>> look usable as specified.
>>>>>
>>>>> Please chime in to correct errors, fill in details.
>>>>>
>>>>> Regards,
>>>>> Alan
>>>>>
>>>>>> In our use case, an investigator reads about the discovery of  
>>>>>> a new form of Abeta, called Abeta*56, that is reported to  
>>>>>> cause memory impairment in a mouse model of AD. (DS1 -  
>>>>>> Alzheimer Research Forum News)
>>>>>
>>>>> It isn't clear in what sense DS1 is a data set to be used in  
>>>>> the use case. Are we expecting that DS1 is to be represented as  
>>>>> RDF? If so, this is something of a challenge, as it is  
>>>>> primarily free text.
>>>>>
>>>>>> Question: Is there human data to support that Abeta*56 is  
>>>>>> involved.
>>>>>>
>>>>>> A query of PubMed (DS2 - PubMed) finds a paper reporting that  
>>>>>> a form of Abeta with identical molecular weight, called ADDL,  
>>>>>> is elevated by as much as 70-fold in human AD patients'  
>>>>>> cerebrospinal fluid. A hypothesis about ADDL causing memory  
>>>>>> loss in AD is posted on Alzforum.
>>>>> I'm not sure how to encode pubmed (free text + mesh terms)  in  
>>>>> such a way as to successfully make this query. The pmids for  
>>>>> the papers cited in the HCLSIG paper, and their searchable  
>>>>> annotations are below. I've condensed this from the XML  
>>>>> representation of the record, specifically the <ChemicalList >,  
>>>>> and the <MeshHeadingList>. To do this query the annotations  
>>>>> would at least have to mention something to do with memory  
>>>>> impairment and Abeta*56, which neither do.
>>>>>
>>>>> PMID:15695586
>>>>>
>>>>> Chemical: Amyloid beta-Protein, Biological Markers, Ligands, DNA
>>>>> Topic:Alzheimer Disease, *cerebrospinal fluid,diagnosis,genetics
>>>>> Topic:Amyloid beta-Protein,*cerebrospinal fluid,genetics,
>>>>> Topic:Base Sequence
>>>>> Topic:Biological Markers,cerebrospinal fluid
>>>>> Topic:Case-Control Studies
>>>>> Topic:DNA,genetics
>>>>> Topic:Humans
>>>>> Topic:Ligands
>>>>> Topic:Nanotechnology
>>>>> Topic:Polymerase Chain Reaction,methods,statistics & numerical  
>>>>> data
>>>>> Topic:Sensitivity and Specificity
>>>>> Topic:Solubility
>>>>>
>>>>> PMID: 9163350
>>>>>
>>>>> Chemical: Amyloid,Nerve Tissue Proteins,Protein Precursors,
>>>>>    SNCA protein- human,SNCB protein- human,Synucleins,alpha- 
>>>>> Synuclein,
>>>>>    beta-Synuclein,Biotin
>>>>> Mesh:Amyloid,*metabolism
>>>>> Mesh:Binding Sites
>>>>> Mesh:Biotin
>>>>> Mesh:Electrophoresis, Polyacrylamide Gel
>>>>> Mesh:Humans
>>>>> Mesh:Nerve Tissue Proteins,*metabolism
>>>>> Mesh:Protein Precursors,*metabolism
>>>>> Mesh:Spectrometry, Mass, Matrix-Assisted Laser Desorption- 
>>>>> Ionization
>>>>> Mesh:Synucleins
>>>>> Mesh:alpha-Synuclein
>>>>> Mesh:beta-Synuclein
>>>>>
>>>>>> Question: By what mechanism might Abeta*56 cause memory loss?
>>>>>>
>>>>>> The ADDL Hypothesis on Alzforum suggests that ADDL (=  
>>>>>> Abeta*56?) disrupts LTP.
>>>>> I think we have to parse free text to determine this. I don't  
>>>>> know ho
>>>>>> Question: What is the mechanism of LTP, in a part of the brain  
>>>>>> that is relevant to AD?
>>>>>>
>>>>>> The literature indicates CA1 hippocampal neurons, and A- and D- 
>>>>>> type K channels are involved in LTP. BrainPharm (DS3 -  
>>>>>> Senselab BrainPharm) data state that CA1 hippocampal neurons  
>>>>>> have A-channels. What's more, the A-current is reduced by Abeta.
>>>>> Verified(second sentence): http://senselab.med.yale.edu/ 
>>>>> senselab/BrainPharm/alzData.asp
>>>>>> Question: Would an antibody directed against ADDL / Abeta*56  
>>>>>> restore A-current in the mouse model hippocampal neuron (e.g.  
>>>>>> in an organotypic slice prep)?
>>>>>>
>>>>>> A query locates an antibody (DS4 - Alzheimer Research Forum  
>>>>>> Antibody Database) to ADDL and where to obtain it.
>>>>> Could search here by name, and succeed. However ADDL isn't an  
>>>>> entity that is given an identifier in any of the standard  
>>>>> databases I am aware of, so we do have an issue to deal with  
>>>>> here. Antibody db conversion focuses on proteins whose gene ids  
>>>>> can be found.
>>>>>
>>>>>> Our investigator queries pathway databases to identify the  
>>>>>> gene network involved in IFNG regulation, and also SNP  
>>>>>> databases for differences between mouse strains, mouse and  
>>>>>> human (DS5 -GeneNetwork, DS6 - KEGG). He narrows down a group  
>>>>>> of genes and queries the AlzGene (DS7 - AlzGene) database to  
>>>>>> see if any gene association studies have shown a correlation  
>>>>>> between any of these genes and AD risk.
>>>>>
>>>>> Verified(IFNG): Could start here for interferon gamma, which  
>>>>> links to several pathways in KEGG. http://www.genome.jp/dbget- 
>>>>> bin/www_bget?hsa+3458
>>>>>
>>>>> Wasn't sure how to use GeneNetwork. Verified that Alzgene links  
>>>>> Gene/SNP to association study.
>>>>>
>>>>>
>>>>>
>>>>>
>>>>>
>>>>>
>>>>>
>>>>>
>>>>>
>>>>>
>>>>>
>>>>>
>>>>
>>>>
>>>
>>
>>
>>
>
Received on Tuesday, 23 January 2007 14:49:32 UTC

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