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Re: AD Use Case

From: Alan Ruttenberg <alanruttenberg@gmail.com>
Date: Sun, 21 Jan 2007 16:06:46 -0500
Message-Id: <22134A14-D507-4CF4-B788-D35CC3CFB3A7@gmail.com>
Cc: Tim Clark <twclark@nmr.mgh.harvard.edu>, public-semweb-lifesci <public-semweb-lifesci@w3.org>
To: June Kinoshita <junekino@media.mit.edu>

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.


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 21:07:04 UTC

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