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Re: AD Use Case

From: Tim Clark <twclark@nmr.mgh.harvard.edu>
Date: Sun, 21 Jan 2007 09:59:36 -0500
Message-Id: <4DAAD98A-C237-41BB-9BA4-AA421E04CCC0@nmr.mgh.harvard.edu>
Cc: public-semweb-lifesci <public-semweb-lifesci@w3.org>
To: Alan Ruttenberg <alanruttenberg@gmail.com>

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.
>
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Received on Sunday, 21 January 2007 14:59:52 UTC

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