Re: AD Use Case

Sun, 21 Jan 2007 13:07:35 -0800 


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.











































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