Re: AD Use Case

Sorry for the delayed reply on this. There's now an entry for an ADDL  
antibody in the Alzforum Antibody database. Does that help?

June

On Jan 21, 2007, at 4:33 PM, Tim Clark wrote:

> 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.
>
> Tim
>
> 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 Tuesday, 23 January 2007 14:49:32 UTC