Re: [BIONT] Teleconference on Tuesday, 5th September 2006

Hi Kei,

Yes - "pigmented" is a problematic property for neurons, but it is  
one that many neurons demonstrate, especially in invertebrates.   
Typically in mammals, such pigmentation is a melanin polymer  
deposition.  This is called "eumelanin" when found in epidermal cells  
responsible for differences in skin color (melanocytes), and  
neuromelanin when found in certain neurons in the deep nuclei of the  
CNS (http://en.wikipedia.org/wiki/Melanin).  It is not surprising  
dopamine and noradrenaline containing neurons would contain melanin,  
since melanin is also derived from tyrosine biosynthetic pathways via  
a DOPA intermediate.

TH is definitely an enzyme and would be associated with dopamine  
metabolism.  Mutations in the TH gene are associated with several  
disorders, including a highly specialized form of Parkinsonian  
Syndrome - infantile onset Parkinsonism.  Regardless, the neurons in  
the substantia nigra known to be lost in quantity in most forms of  
Parkinsonian Syndrome are TH+ cells, so they provide a useful  
histological marker for pathologists and for neuroscientist using  
histological techniques to study the disease in animal models.

Tyrosine Hydroxylase is the name by which many neuroanatomists and  
neurophysiologists will know the enzyme - the name by which many  
histological techniques and antibody probes for TH will be labeled.   
Unfortunately, most enzyme and pathway knowledge sources will list it  
according the precise enzymatic activity it provides - tyrosine 3- 
monooxygenase, so using "tyrosine hydroxylase" can be problematic.   
Fortunately, such info is cross-referenced as synonomies in the Gene  
Ontology:

Gene Ontology: GO:0004511 -  Tyrosine hydroxylase activity
http://www.godatabase.org/cgi-bin/amigo/go.cgi? 
view=details&search_constraint=terms&depth=0&query=GO: 
0004511&session_id=1405b1157493522

TH is also important in NA containing neurons such as those in the  
Locus Coeruleus, as NA is one of the downstream products of dopamine  
in the catecholamine biosynthetic pathway.
	http://www.anaesthetist.com/anaes/patient/ans/nadr.htm
	http://web.indstate.edu/thcme/mwking/aminoacidderivatives.html

See also the OMIM reference to TH
http://www.ncbi.nlm.nih.gov/entrez/dispomim.cgi?id=191290

With all of these issues in mind, when it comes to defining the  
relevant properties of neurons, it is sensible to look toward the  
PaTO to describe these properties.

I've created a detailed follow-up Wiki page to Vipul's Seed Ontology  
page.  Over the next day or so, I will fill out the entities using  
the emerging OBO Foundry (http://obofoundry.org/) "best practices" -  
which include reference to foundation ontology layer now being used  
for FMA, OBI/FuGO, PaTO, the Sequence Ontology, and the BIRN  
ontologies we are building to fill in the gaps in neuro not covered  
by existing community ontologies supporting the OBO Foundry  
approach.  The Gene Ontology is being adapted to use this approach as  
well.  One of the things we've been doing in the BIRN Ontology Task  
force is to use the NeuroNames neuroanatomical thesaurus since it  
covers nearly all the detail we require for mouse and human  
mesoscopic anatomy, but assemble it in a subsumptive graph that holds  
to the OBO Foundry principles.

So - I will do three things:

	1) layout the entities Vipul has assembled so far in this format,  
using the community ontologies.  As Alan suggested, I will be  
switching to using Protege-OWL, so that the resulting ontology will  
be in OWL.  This can also be turned out using the OWLDoc plugin to  
provide Javadoc style hierarchical HTML layout for browsing the  
resulting ontology.  I will also make reference to the public  
ontologies, terminologies from which these entities (and their  
definitions - critical - as Alan pointed out) derive.  90% of what we  
are dealing with here are covered, some major community constructed  
biomedical ontologies - others by more individually research based  
ontologies, such as the wonderful cell type framework being assembled  
both by the SenseLab group at Yale and the Cell Centered Database at  
UCSD.  We may also be able to use certain aspects of the EBI  
sponsored Cell Type ontology (http://www.ebi.ac.uk/ontology-lookup/ 
browse.do?ontName=CL).

	2) Select several research articles making statements - based on  
research reported in those articles - that includes these entities  
and their relation to Parkinsonian Syndrome.

	3) Express those statements using the PaTO format

I will try to take 1 to completion (not filling out a complete  
ontology, but covering all entities necessary to create a complete  
subsumptive graph for the entities we're focussing on.  For instance,  
if we say we need to handle biomaterial entities such as cells and  
extracellular structures (Lewy Body) that occur in the Cerebellar  
cortex, Substantia nigra, and the Locus coeruleus, then I will fill  
out those entities in the neuroanatomical subsumptive graph required  
to drill down to those 3 brain regions - as opposed to representing  
ALL of regions in the mammalian brain.

'2' & '3' are just examples meant to help ground us with a real-world  
context.  I don't expect to do more than a couple of PaTO examples  
prior to our next meeting, so we'll have a chance to review this  
together and see whether everyone feels this is workable and fits to  
our requirements, so of which will need to be fully fleshed out in  
collaboration with the BioRDF group based on the sources they are  
identifying.

I am specifically avoiding more complex levels such as pathways and  
SPE-related study artifacts.  We must and will get to them, but I  
think we want to start with as a close a tie to the real-world  
entities identified and work our way up from there.  Many of the  
complex graphs already exist - the pathways - and gene networks and  
others such as mereotopological relations for neuroanatomy - can be  
layered on top, but we must get these foundational subsumptive graphs  
down first, at least for this subset of entities.

I'll let folks know when this page is ready for review - within the  
next few days.

Cheers,
Bill



On Sep 5, 2006, at 4:53 PM, kei cheung wrote:

> Dear Bill et al.,
>
> Thanks for the articles and the explanation. I agree that we should  
> consider mutliple brain regions in the case of Parkinson's Disease  
> (as well as other neurological diseases). I just gave a specific  
> example (purkinje cell is located in cerebellum).  There are other  
> types of neurons located in other brain regions. At the ontology  
> level, we probably should have a neuron class that has an  
> "is_located_in" property linking to the brain-region class  
> (neuronames can be a candidate standard taxonomy of brain regions).  
> Also you mentioned that neuron has another property "contains". For  
> example, dopaminergic_neuron contains tyrosine_hydroxylase  which  
> is an enzyme. The interesting question here is that should we treat  
> tyrosine_hydroxylase as a subclass or instance of the enzyme class?  
> Also, another related question is that what can a neuron contain  
> (pigment is not an enzyme)? Just my 2-cent thought.
>
> Best,
>
> -Kei
>
> William Bug wrote:
>
>> Absolutely, thanks Kei!
>>
>> Though - for Parkison's - we're going to need to deal with neurons  
>> in the substantia nigra and the locus coeruleus.  For instance, see:
>>
>> Relationship among alpha-synuclein accumulation, dopamine  
>> synthesis, and neurodegeneration in Parkinson disease substantia  
>> nigra.
>> Mori F, Nishie M, Kakita A, Yoshimoto M, Takahashi H,  Wakabayashi K
>> http://www.ncbi.nlm.nih.gov/entrez/query.fcgi? 
>> db=pubmed&cmd=Retrieve&dopt=AbstractPlus&list_uids=16896314&query_hl= 
>> 32&itool=pubmed_docsum <http://www.ncbi.nlm.nih.gov/entrez/ 
>> query.fcgi? 
>> db=pubmed&cmd=Retrieve&dopt=AbstractPlus&list_uids=16896314&query_hl= 
>> 32&itool=pubmed_docsum>
>>
>> One of the problems with these areas of the brain is the cell  
>> types are much less clearly characteristic than cerebellar  
>> Purkinje neurons.  They aren't completely without distinctive  
>> character and some details can be given, as they are in the above  
>> research article:
>>
>> :neuron :contains :pigment
>> :neuron :contains :tyrosine_hydroxylase
>>
>> It's just neither of these are properties commonly used to  
>> classify neuronal type, though the latter is a property of:
>>
>> :neuron :is_a :dopaminergic_neuron
>>
>> but as Gordon Shepherd and Michele Migliore have pointed out, this  
>> tradition of typing neurons by transmitter is very problematic:
>>
>> http://www.ncbi.nlm.nih.gov/entrez/query.fcgi? 
>> db=pubmed&cmd=Retrieve&dopt=AbstractPlus&list_uids=11988775&query_hl= 
>> 35&itool=pubmed_docsum <http://www.ncbi.nlm.nih.gov/entrez/ 
>> query.fcgi? 
>> db=pubmed&cmd=Retrieve&dopt=AbstractPlus&list_uids=11988775&query_hl= 
>> 35&itool=pubmed_docsum>
>>
>> Oops - time to call in.
>>
>> Cheers,
>> Bill
>>
>>
>> On Sep 5, 2006, at 10:42 AM, Kashyap, Vipul wrote:
>>
>>> Thanks, Kei Cheung!
>>>
>>> This is one of the design issues I had raised. The issue of  
>>> granularity is a
>>> very important one, and you have provided an interesting use case.
>>>
>>> Regards,
>>>
>>> ---Vipul
>>>
>>> =======================================
>>> Vipul Kashyap, Ph.D.
>>> Senior Medical Informatician
>>> Clinical Informatics R&D, Partners HealthCare System
>>> Phone: (781)416-9254
>>> Cell: (617)943-7120
>>> http://www.partners.org/cird/AboutUs.asp?cBox=Staff&stAb=vik  
>>> <http://www.partners.org/cird/AboutUs.asp?cBox=Staff&stAb=vik>
>>>
>>> To keep up you need the right answers; to get ahead you need the  
>>> right questions
>>> ---John Browning and Spencer Reiss, Wired 6.04.95
>>>
>>>> -----Original Message-----
>>>> From: kei cheung [mailto:kei.cheung@yale.edu]
>>>> Sent: Tuesday, September 05, 2006 10:41 AM
>>>> To: Kashyap, Vipul
>>>> Cc: William Bug; public-semweb-lifesci@w3.org <mailto:public- 
>>>> semweb-lifesci@w3.org>
>>>> Subject: Re: [BIONT] Teleconference on Tuesday, 5th September 2006
>>>>
>>>> Hi Vipul, Bill et al.,
>>>>
>>>> Thanks for your efforts. I think the seed (global) ontology is a  
>>>> good
>>>> start. I'd also suggest to include modeling at the neuronal  
>>>> level that
>>>> allows study of neuronal properties that are involved in Parkinson
>>>> Disease. For example, the following OWL ontology
>>>>
>>>> <owl:Class rdf:ID="#Cerebellar_purkinje_cell">
>>>> <owl:equivalentClass>
>>>> <owl:intersectionOf >
>>>> <owl:Class rdf:id="purkinje neuron" />
>>>> <owl:Restriction>
>>>> <owl:onProperty rdf:resource="#locatedInBrainRegion" />
>>>> <owl:allValuesFrom
>>>> rdf:resource="#Cerebellum" />
>>>> </owl:Restriction>
>>>> <owl:intersectionOf />
>>>> </owl:equivalentClass>
>>>> </owl:Class>
>>>>
>>>> It captures the knowledge that there are purkinje cells located  
>>>> in the
>>>> cerebellum region of the brain. The interesting thing is that  
>>>> NeuronDB
>>>> and CCDB, for example, represent this knowledge differently. In
>>>> NeuronDB, there is a concept called "CerebellarPurkinjeNeuron",  
>>>> while in
>>>> CCDB it's broken down into the following triples: PurkinjeNeuron,
>>>> locatedInBrainRegion, Cerebellum. The above OWL ontology (or  
>>>> bridging
>>>> ontology) indicates how to use the equivalentClass construct to
>>>> establish mapping between NeuronDB and CCDB. OWL is just one way  
>>>> to do
>>>> it. There are also other ways to do the same thing.
>>>>
>>>> Cheers,
>>>>
>>>> -Kei
>>>>
>>>> Kashyap, Vipul wrote:
>>>>
>>>>> For the time being, I have uploaded the JPEG and GIF versions  
>>>>> of the
>>>>> Ontology in UML.
>>>>>
>>>>> ---Vipul
>>>>>
>>>>> ------------------------------------------------------------------ 
>>>>> ------
>>>>>
>>>>> *From:* William Bug [mailto:William.Bug@DrexelMed.edu]
>>>>> *Sent:* Tuesday, September 05, 2006 12:01 AM
>>>>> *To:* Kashyap, Vipul
>>>>> *Cc:* public-semweb-lifesci@w3.org <mailto:public-semweb- 
>>>>> lifesci@w3.org>
>>>>> *Subject:* Re: [BIONT] Teleconference on Tuesday, 5th September  
>>>>> 2006
>>>>>
>>>>> Many thanks, Vipul.
>>>>>
>>>>> I think this is a nice, concrete start and will certainly  
>>>>> provide a
>>>>> solid foundation for discussion as we move forward - as will the
>>>>> Design Issues page you've created.
>>>>>
>>>>> If it's OK, I'd like to make a small request re: the UML file.  
>>>>> I see
>>>>> MS has created an XMI export feature for Visio
>>>>> (http://www.microsoft.com/downloads/details.aspx? 
>>>>> FamilyID=3DD3F3BE-656D-
>>>>
>>>> 4830-A868-D0044406F57D&displaylang=en
>>>>
>>>>> <http://www.microsoft.com/downloads/details.aspx? 
>>>>> FamilyID=3DD3F3BE-656D-
>>>>
>>>> 4830-A868-D0044406F57D&displaylang=en>).
>>>>
>>>>> Would it be possible for you to export the UML from Visio in XMI
>>>>> format? This way I'll be able to use one of several open source
>>>>> modeling tools that use XMI as there persistence file format. I  
>>>>> assume
>>>>> I'm not the only one on the list without a copy of Visio on  
>>>>> hand. I
>>>>> expect there may be some associations that don't translate  
>>>>> perfectly,
>>>>> but as it now stands, I'm not able to take advantage of the  
>>>>> fruit's of
>>>>> your labor. As a side note, I often provide a PNG version when
>>>>> distributing models, just so others who either don't have the  
>>>>> tools or
>>>>> the knowledge of how to use open source equivalents can at  
>>>>> least view
>>>>> the model in a web browser.
>>>>>
>>>>> Many thanks again. I think it will be immensely helpful to have  
>>>>> made
>>>>> this concrete step forward. It also provides the BioRDF WG an
>>>>> opportunity to comment on how this ontology will mesh with the
>>>>> requirements they've been identifying for the Parkinsonian
>>>>> Syndrome-related data sources.
>>>>>
>>>>> Cheers,
>>>>>
>>>>> Bill
>>>>>
>>>>> On Sep 4, 2006, at 10:43 PM, Kashyap, Vipul wrote:
>>>>>
>>>>>
>>>>>
>>>>> BIONT Teleconference on Tuesday, 5^th September from 11:00am -  
>>>>> 12:00pm
>>>>> US Eastern
>>>>>
>>>>> Phone: +1 617 761 6200, conference 24668 ("BIONT")
>>>>>
>>>>> IRC irc://irc.w3.org:6665/hcls
>>>>>
>>>>> Browser-based IRC client: http://www.w3.org/2001/01/cgi-irc
>>>>>
>>>>> *Agenda:*
>>>>>
>>>>> We will discuss the initial "seed ontology" for the Bench to  
>>>>> Bedside
>>>>> Ontology
>>>>>
>>>>> This is based on the use case specification available at:
>>>>>
>>>>> http://esw.w3.org/topic/HCLS/ParkinsonUseCase
>>>>>
>>>>> We will focus on the Cellular and Molecular Biologist view.
>>>>>
>>>>> The seed ontology is available at:
>>>>>
>>>>> http://esw.w3.org/topic/HCLS/OntologyTaskForce/SeedOntology
>>>>>
>>>>> The seed ontology in the UML format (Visio File) is available at:
>>>>>
>>>>>
>>>> http://esw.w3.org/topic/HCLS/OntologyTaskForce/SeedOntology? 
>>>> action=AttachF
>>>> ile&do=get&target=SeedOntologyUML.vsd
>>>>
>>>>>
>>>> <http://esw.w3.org/topic/HCLS/OntologyTaskForce/SeedOntology? 
>>>> action=Attach
>>>> File&do=get&target=SeedOntologyUML.vsd>
>>>>
>>>>>
>>>>> A discussion of Design Choices and other issues is available at:
>>>>>
>>>>> http://esw.w3.org/topic/HCLS/OntologyTaskForce/DesignIssues
>>>>>
>>>>> Cheers,
>>>>>
>>>>> ---Vipul
>>>>>
>>>>> =======================================
>>>>>
>>>>> Vipul Kashyap, Ph.D.
>>>>>
>>>>> Senior Medical Informatician
>>>>>
>>>>> Clinical Informatics R&D, Partners HealthCare System
>>>>>
>>>>> Phone: (781)416-9254
>>>>>
>>>>> Cell: (617)943-7120
>>>>>
>>>>> http://www.partners.org/cird/AboutUs.asp?cBox=Staff&stAb=vik  
>>>>> <http://www.partners.org/cird/AboutUs.asp?cBox=Staff&stAb=vik>
>>>>> <http://www.partners.org/cird/AboutUs.asp?cBox=Staff&stAb=vik  
>>>>> <http://www.partners.org/cird/AboutUs.asp?cBox=Staff&stAb=vik>>
>>>>>
>>>>> To keep up you need the right answers; to get ahead you need  
>>>>> the right
>>>>> questions
>>>>>
>>>>> ---John Browning and Spencer Reiss, Wired 6.04.95
>>>>>
>>>>>
>>>>>
>>>>> Bill Bug
>>>>>
>>>>> Senior Research Analyst/Ontological Engineer
>>>>>
>>>>> Laboratory for Bioimaging & Anatomical Informatics
>>>>>
>>>>> www.neuroterrain.org
>>>>>
>>>>> Department of Neurobiology & Anatomy
>>>>>
>>>>> Drexel University College of Medicine
>>>>>
>>>>> 2900 Queen Lane
>>>>>
>>>>> Philadelphia, PA 19129
>>>>>
>>>>> 215 991 8430 (ph)
>>>>>
>>>>> 610 457 0443 (mobile)
>>>>>
>>>>> 215 843 9367 (fax)
>>>>>
>>>>> Please Note: I now have a new email - William.Bug@DrexelMed.edu  
>>>>> <mailto:William.Bug@DrexelMed.edu>
>>>>> <mailto:William.Bug@DrexelMed.edu>
>>>>>
>>>>>
>>>>>
>>>>> This email and any accompanying attachments are confidential.
>>>>> This information is intended solely for the use of the individual
>>>>> to whom it is addressed. Any review, disclosure, copying,
>>>>> distribution, or use of this email communication by others is  
>>>>> strictly
>>>>> prohibited. If you are not the intended recipient please notify us
>>>>> immediately by returning this message to the sender and delete
>>>>> all copies. Thank you for your cooperation.
>>>>>
>>>>
>>>
>>
>> Bill Bug
>> Senior Research Analyst/Ontological Engineer
>>
>> Laboratory for Bioimaging  & Anatomical Informatics
>> www.neuroterrain.org
>> Department of Neurobiology & Anatomy
>> Drexel University College of Medicine
>> 2900 Queen Lane
>> Philadelphia, PA    19129
>> 215 991 8430 (ph)
>> 610 457 0443 (mobile)
>> 215 843 9367 (fax)
>>
>>
>> Please Note: I now have a new email - William.Bug@DrexelMed.edu  
>> <mailto:William.Bug@DrexelMed.edu>
>>
>>
>>
>>
>> This email and any accompanying attachments are confidential. This  
>> information is intended solely for the use of the individual to  
>> whom it is addressed. Any review, disclosure, copying,  
>> distribution, or use of this email communication by others is  
>> strictly prohibited. If you are not the intended recipient please  
>> notify us immediately by returning this message to the sender and  
>> delete all copies. Thank you for your cooperation.
>>
>
>

Bill Bug
Senior Research Analyst/Ontological Engineer

Laboratory for Bioimaging  & Anatomical Informatics
www.neuroterrain.org
Department of Neurobiology & Anatomy
Drexel University College of Medicine
2900 Queen Lane
Philadelphia, PA    19129
215 991 8430 (ph)
610 457 0443 (mobile)
215 843 9367 (fax)


Please Note: I now have a new email - William.Bug@DrexelMed.edu







This email and any accompanying attachments are confidential. 
This information is intended solely for the use of the individual 
to whom it is addressed. Any review, disclosure, copying, 
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prohibited. If you are not the intended recipient please notify us 
immediately by returning this message to the sender and delete 
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