Summary:
We reviewed the use case, and then, starting in one area of the use
case - the connection between ADDL and impairment of long term
potentiation deficits - highlighted on page 2 of the updated use case
[1] - and started to trace out a series of steps that lead towards
determining relevant sets of gene and then to images of expression
of those genes. Along the way we reviewed web pages and databases to
verify what information was available. We then collected a list of on
line databases that would enable
the kinds of queries we were exploring.
[1] http://esw.w3.org/topic/HCLSIG_BioRDF_Subgroup/Demo_Thoughts/
Alzheimer%27s_Proposal?
action=AttachFile&do=get&target=AD_PDUseCase_02-26-07.pdf
Start:
Hypothesis+Abeta -> ADDL (SWAN. Note that these areas of SWAN are not
yet populated but June and Gwen are working on this).
We attempted to linking ABeta to LTP, but this did not find the
requisite links. What we did was:
Go to http://senselab.med.yale.edu/senselab/modeldb/. Search for
"ltp" (could also search for "long term potentiation"
This is a text search, and the matches are typically against the
titles of citations.
Each result links to a model, which lists some cell types, some
receptor families, some transmitters.
We reviewed the receptors and searched for them in NeuronDB but did
not find links to processes such as long term potentiation.
--- Starting over
Go to http://senselab.med.yale.edu/BrainPharm/eavData.asp?
db=1&c=122&o=5904
Links from Alzheimer's disease to CA1 Pyramidal Neuron
Click on CA1 Pyramidal Neuron
Link to http://senselab.med.yale.edu/BrainPharm/NeuronDB/
ndbEavSum.asp?id=5588&mo=4&re=
CA1 Pyramidal Neuron Extracellular Elements : Abeta (current I A)
CA1 Pyramidal Neuron Intrinsic Currents : I A. Click on I A.
http://senselab.med.yale.edu/BrainPharm/eavData.asp?o=5545
Links to K+
Need to know that current of K+ is carried by Potassium Channels.
However, even though some text indicates LTP, there is no explicit
link. We do have a link from neurons of interest
to genes however, if we are able to look up proteins associated with
potassium channel function.
Browse GO we do find these associations.
---- Approach using LTP as a key from a different direction.
There is a mesh term
http://www.nlm.nih.gov/cgi/mesh/2007/MB_cgi?mode=&term=Long-Term
+Potentiation&field=entry
We can link to pubmed papers using mesh term headings.
http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?
CMD=search&DB=pubmed&term=Long-Term+Potentiation%5Bmh%5D&cmd
There is also Potassium Channel
http://www.nlm.nih.gov/cgi/mesh/2007/MB_cgi?mode=&term=Potassium
+Channels&field=entry
and Pyramidal cells
http://www.nlm.nih.gov/cgi/mesh/2007/MB_cgi?mode=&term=Pyramidal
+Cells&field=entry
So if we have a Pubmed -> Mesh mapping, we are able to use this to
navigate from mesh term to mesh term,
for example, from LTP to cell types or to channel types.
This also requires that we have the MESH tree encoded. Note, however,
that this MESH->MESH links are potentially unreliable
as they could be the product of unrelated discussions in the paper
used to do the mapping.
--- From pubmed to genes.
We can also go from pubmed to gene. This is seen in the user
interface via the "links" button on a pubmed abstract page.
e.g.
http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?
db=pubmed&cmd=Retrieve&dopt=AbstractPlus&list_uids=17251421&query_hl=5&i
tool=pubmed_docsum
Choose links, then gene, then you get:
http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?
itool=pubmed_AbstractPlus&db=pubmed&cmd=Display&dopt=pubmed_gene&from_ui
d=17251421
The mapping of pubmed -> gene is not in the pubmed records, but is
kept on the gene side.
There are entries in the Entrez gene asn or xml record, as well as
the generifs, which associate a gene with a paper.
Along with the Gene ontology, we now have two ways to navigate from
"Potassium channel" to gene.
-- From gene to brain region
We can get BrainRegion from gene in a number of ways:
Using expression data: The Allen Brain Map has, for a select group of
regions and structures, lists of genes
expressed in those structures. Some of these are at:
http://community.brain-map.org/confluence/display/DataAnno/Home
Others can be scraped from the results of queries at http://brain-
map.org/welcome.do (click on the "Anatomic Search" tab)
(Alan has these)
Similarly, Gensat (ftp://ftp.ncbi.nih.gov/RawData/
GENSAT-20050125.xml.gz) Has images associated with genes
and annotations that say which areas/cell types have which patterns
of expressions of those genes.
(Alan has these)
--- From Cell type to brain region.
In addition to the mappings implicit in Gensat,
BAMS http://brancusi.usc.edu/bkms/xml/swanson-98.xml has mappings of
cell types to brain regions
-- Another route for getting Alzheimer related genes:
We can also get from Alzheimer to gene via Alzgene
There is a popup of genes on http://www.alzforum.org/res/com/gen/
alzgene/default.asp, which records
studies which find associations between mutations of these genes with
Alzheimer disease.
--- Some other resources
We will want human to mouse gene mappings for better navigating from
pubmed.
Available at: http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?
db=homologene
For linking gene to protein and protein products such as cleaved
proteins, June has started curating these from various sources.
Uniprot has such mapping, it is only textual. See, e.g., http://
www.pir.uniprot.org/cgi-bin/upEntry?id=P05067. Look for the
"contains" field.
Another resource for relating phenotype, process to genes is the JAX
Mammalian Phenotype ontology/
Associated with each phenotype, are the alleles/genes associated with
the phenotype.
http://www.informatics.jax.org/searches/MP_form.shtml
For example, abnormal hippocampus function http://
www.informatics.jax.org/javawi2/servlet/WIFetch?
page=mpAnnotSummary&id=MP:0001895
Gwen and Don will review the terms to see which would be relevant to
processes associated with Alzheimers, and this gives us another
route to narrow/expand genes of interest.
Summarizing data sources which we will use for the next step of
exploration. Some we have, some we need to acquire/convert to RDF.
Mesh
Pubmed -> Mesh Term
GO -> Associations (Genes)
Entrez Gene -> Pubmed
Entrez GeneRif (= gene->Pubmed)
NeuronDB/Brainpharm
Homologene
Alzgene (Alzheimer Disease -> Associated Gene)
JAX: Mouse Phenotpe -> Gene
Uniprot Gene-> splice form, gene product.
BAMS swanson-98.xml
Allen/Gensat gene->image, gene-> regions/expressed
Alan's comment: Process for conversion to RDF should be 2 step
1) Propose model, give sample entry for review
2) Upon agreement on model translate rests/load into triple store for
query.
Action: Candidates for doing conversions: Alan, EricP, Matthias, Don
(?) to talk and split tasks.
Action: Don and Gwen to review phenotypes
Action: June to curate trying to write pseudo-triples to make
conversion to real triples easier.
-Alan