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Re: AD Use Case

From: Tim Clark <twclark@nmr.mgh.harvard.edu>
Date: Sun, 21 Jan 2007 16:33:47 -0500
Message-Id: <77CD1D5F-8BDD-45F5-B159-4F3786F59878@nmr.mgh.harvard.edu>
Cc: June Kinoshita <junekino@media.mit.edu>, public-semweb-lifesci <public-semweb-lifesci@w3.org>
To: Alan Ruttenberg <alanruttenberg@gmail.com>

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.


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 Sunday, 21 January 2007 21:34:09 UTC

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