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Re: Notes from informal Demo F2F

From: Twigger Simon <simont@hmgc.mcw.edu>
Date: Tue, 6 Mar 2007 08:42:50 -0600
Message-Id: <C445E298-FDD9-4033-B3C0-CD7FC48BC601@hmgc.mcw.edu>
Cc: public-semweb-lifesci@w3.org
To: Alan Ruttenberg <alanruttenberg@gmail.com>

Dear All,

I've been lurking on list for a while and saw this email and wanted  
to chime in briefly. I have a few other suggestions for some of your  
'Other Resources' that we have at the Rat Genome Database. We have  
rat genes annotated with the Mammalian Phenotype ontology, along with  
a disease ontology derived from MeSH, GO and a pathway ontology we've  
been putting together in house. We also pull in and annotate genes  
from Rat, Mouse and Human where we can to try and give a broader view  
from the three species.

You can search any of the ontologies by starting here:
http://rgd.mcw.edu/tools/ontology/ont_search.cgi

The Alzheimer's entry via the disease ontology is here:
http://rgd.mcw.edu/tools/ontology/ont_annot.cgi? 
term_key=54285&ontology=do

For this area in particular we also have a Neurological Diseases  
portal which gives a different view on the disease data:
http://rgd.mcw.edu/dportal/neurological/

This data was derived from a focused curation effort looking at rat  
genes involved in neurological diseases and then branching out to  
include human and mouse data where available. Much of the human data  
came from our curation, Mouse came from MGD.

To get to the Alzheimer's entry you need to select:
1. Neurodegenerative Diseases for the disease category in drop down #1
and then
2. Alzheimer Disease for the disease in drop down menu #2 (excuse the  
typo in the menu's text)

the page should then refresh giving you graphical views of genes  
annotated to Alzheimer's in rat, human and mouse, tables of genes  
from these three species and then a GO slim overview of the rat genes.

If you need raw data instead of web pages or if we can help in any  
other way, please let me know.

Cheers,

	Simon.

--

Simon N. Twigger, Ph.D.
Assistant Professor, Department of Physiology
Medical College of Wisconsin
8701 Watertown Plank Road,
Milwaukee, WI, USA
tel: 414-456-8802
fax: 414-456-6595
AIM/iChat: simontatmcw


On Mar 5, 2007, at 9:35 PM, Alan Ruttenberg wrote:

>
> 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.
>
> -Alan
>
>
>
>
Received on Tuesday, 6 March 2007 20:38:54 GMT

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