Re: BioRDF [Telcon]

Thanks Vipul and Bill for your very encouraging feedback on our use  
case. We know there's a lot of work still needed to flesh it out, and  
it's gratifying to get such positive responses at this early stage.

In answer to Vipul's question about posting hypotheses and querying  
the SWAN knowledge base, we are planning to manually curate  
hypotheses. Each major hypothesis will be broken down into claims, or  
scientific assertions, and linked to supportive evidence, additional  
supportive, refuting or alternative claims, etc. We've been mainly  
focused on creating a scientific discourse ontology and defining the  
relationship terms among the different SWAN objects, but we are  
planning for each claim or type of evidence to be tagged with terms  
from shared ontologies. We'll be thinking a lot about the ontologies  
that will support the type of querying we envision. This is an area  
where many of the HCLSIG community have far greater expertise than we  
have, and we will very much welcome your help!

Re integrating our AD use case with a PD use case, I could imagine  
one where a PD researcher is investigating whether an immunization  
approach could work for PD. There are some strong parallels between  
AD and PD (and indeed, there is significant co-morbidity and  
overlapping pathology). PD is characterized by aggregates of alpha- 
synuclein, and some researchers have reported that there are soluble  
oligomers of alpha-synuclein that may be toxic. The brain regions  
that express alpha-synuclein are different than those that express  
Abeta (I believe the Mouse BIRN has some gorgeous images of GFP- 
tagged alpha-synuclein), there are some interesting mouse models for  
investigating the interaction between alpha-syn and Abeta, and there  
may well be some preclinical studies under way to try alpha-syn  
immunization. If so, I'm sure those folks are carefully watching what  
is going on in AD.

Regards,
June

On Dec 12, 2006, at 3:48 PM, Kashyap, Vipul wrote:

>
> June,
>
> This use case below is a great one. Thanks for sharing it with us!
> I guess some of the questions can be answered using PubMed queries  
> on the
> literature and some of them can be answered using "facts/ 
> hypotheses" stored on
> the Alzheimer's Forum.
>
> I would presume that the act of posting hypotheses on the  
> Alzheimer's Forum
> would be a manual step, but this would later enable automatic  
> answering of other
> queries?
>
> Wondering how one could "integrate" this use case with the  
> Parkinson's Disease
> Use Case snd whether it would be feasible or make sense.
>
> Regards,
>
> ---Vipul
>
> An interesting list of hypotheses that you enumerate are:
>
>> A hypothesis about
>> ADDL causing memory loss in AD is posted on Alzforum.
>
>> The ADDL Hypothesis on Alzforum suggests that ADDL (= Abeta*56?)
>> disrupts LTP.
>
>> The literature indicates CA1 hippocampal neurons, and A- and D-type K
>> channels are involved in LTP. BrainPharm data state that CA1
>> hippocampal neurons have A-channels.  What's more, the A-current is
>> reduced by Abeta.
>>
>> 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 to ADDL and where to obtain it.
>>
>> Question 2 is what determines vulnerability to encephalilitis among
>> immunized patients?
>>
>> A literature search finds interferon-gamma (INFG) may be a player.
>> This comes from both mouse and human trial data (need to check this).
>>
>> Question: Do polymorphisms in INFG, or differences in INFG
>> regulation, correlate with inflammatory response to vaccine?
>>
>> Question: Why did the mouse models not develop encephalitis in
>> preclinical studies?
>>
>> 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. He narrows down a
>> group of genes and queries the AlzGene database to see if any gene
>> association studies have shown a correlation between any of these
>> genes and AD risk.
>>
>> Our investigator proposes a study to genotype participants in the
>> failed vaccination trial to find out whether the encephalitis
>> response correlates with specific SNPs in the candidate genes.
>>
>>
>> On Dec 8, 2006, at 3:16 PM, Susie Stephens wrote:
>>
>>>
>>> Here's a reminder for Monday's BioRDF call.
>>>
>>> Date of Call: Monday December 11, 2006
>>> Time of Call: 11:00am Eastern Time
>>> Dial-In #: +1.617.761.6200 (Cambridge, MA)
>>> Participant Access Code: 246733 ("BIORDF")
>>> IRC Channel: irc.w3.org port 6665 channel #BioRDF
>>> Duration: ~1 hour
>>>
>>> Agenda
>>> Matthias Samwald and Alan Ruttenberg will be providing task updates.
>>> Bill Bug, Elizabeth Wu and Scott Marshall will be discussing the
>>> scientific queries that they have been researching.
>>>
>>> Kind regards,
>>>
>>> Susie
>>>
>>
>

Received on Wednesday, 13 December 2006 21:35:39 UTC