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.