HCLSIG BioRDF Subgroup/Meetings/2007-03-05 Conference Call

Informal F2F

Date of Call: Monday March 5, 2007
Time of Call: 11:30am Eastern Time
Location: 60 Oxford Street, Cambridge, MA. The garage is off Everett St. If you were to be going north on Mass Ave, turn right on Everett, cross Oxford & continue - apparently into the construction site - but it isn't, it is a garage. Ask for the SWAN meeting.
Dial-In #: +1.617.761.6200 (Cambridge, MA)
Dial-In #: +33.4.89.06.34.99 (Nice, France)
Dial-In #: +44.117.370.6152 (Bristol, UK)
Participant Access Code: 246733 ("BIORDF")
IRC Channel: irc.w3.org port 6665 channel #BioRDF (see W3C IRC page for details, or see Web IRC)
Convener: Tim Clark

Preparation

Agenda

Identify subset of demo to implement. The options are:
1) What are the different forms of Abeta? Does Abeta*56 resemble any previously reported form?
2) What mechanism is proposed, and what brain cell types are involved?
3) What synaptic currents are involved in LTP, and are affected by Abeta?
4) What mechanism might account for encephalitis in immunized patients? What genes?
5) Is there a common antigen that would lead to a single immunization therapy for both AD and PD?

Minutes

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&itool=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_uid=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.