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Re: AD Use Case

From: Alan Ruttenberg <alanruttenberg@gmail.com>
Date: Sun, 21 Jan 2007 02:33:43 -0500
Message-Id: <9C4401FA-2CAE-47F7-A02D-154732E86553@gmail.com>
To: public-semweb-lifesci <public-semweb-lifesci@w3.org>

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 07:34:36 UTC

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