Re: AD Use Case

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 20:52:09 UTC