Re: Spatial queries against GENSAT or ABA

Hi Bill, Maryann,

Thanks for your great response to the GIS queries of the brain. I 
absolutely agree it's not a trivial issue to create canonical 
coordinates that will work for different types/instances of brains, 
while there is only one earth! Bill, you're also right on the target for 
my question about correlation between mRNA expression and protein 
expression.

The life science significance and use case of Google Map and Google 
Earth has been described in Nature 
(http://www.nature.com/nature/journal/v439/n7072/full/439006a.html).  
Can we do brain data "mashup" using Google Map (and possibly Google 
Earth)? We might be a step closer, although as Bill indicated there are 
still challenges ahead. It sounds like different groups are actively 
working on different brain visualization tools with GIS querying 
capabilities. That's exciting! The potential of combining GIS and 
semantic web can be huge!

Don't forget literature and scientific publishing! Tools like Connotea 
and Google Earth can interoperate. A bunch of papers describing 
genetic/epidemiologic research studies based on different human 
populations can be bookmarked using Connotea and tagged with 
geographical coordinates (geo tag). Google Earth can then recognize such 
geo-tags and display the geographical distribution of such populations 
with different satellite images superimposed.

I need to dream more about the data/tool mashup.

Good night,

-Kei

William Bug wrote:

> Given the UNIQUE work BIRN, your lab, and Ilya have done in applying 
> GIS techniques to this problem of creating a SPATIAL-QUERY capable 
> brain atlasing system (the SMART Atlas), it would be wonderful if Ilya 
> could vet the scenarios as I outline them below.  This is my best 
> understanding of what is required, but it may be very 3D-biased 
> because of the work we do at Drexel.  To my mind, the problem is the 
> same, only the strategies for solving it are a little be different - 
> in some ways more tractable in 2D - though the answers may come with 
> more constraints.
>
> I did pass some emails around to the SMART Atlas folks early last 
> week in order to get their feedback on Alan's work on the Google Maps 
> Javascript API and backend PERL code to support caching images.  The 
> Google Maps API is one that has come up endless in these atlasing 
> discussions, and it's nice to see just how it can be made useful - 
> what it can and cannot do in this application space.
>
> As Maryann states - and I've stated several times - there is ONGOING 
> work on several projects seeking to provide this functionality applied 
> to the ABA and GENSAT gene expression image data repositories.  None 
> of it - that I'm aware of - would be ready for use by the first week 
> in May - or really at least a month before - to test.  I do think 
> there are other low-hanging fruit, tractable opportunities in the time 
> frame of for the HCLS IG demo for which SemWebTech is specifically 
> suited, and Alan is converging on several of them.
>
> Cheers,
> Bill
>
>
> On Mar 4, 2007, at 1:44 PM, Maryann Martone wrote:
>
>> This is exactly what BIRN has been working on through the Smart Atlas 
>> project and now MBAT.  The inverse query is also true:  What genes 
>> are expressed here?  As Bill indicated, there are several spatially 
>> normalized atlas projects (ABA, GEnepaint) that can do that.  We've 
>> been working on spatial normalization of some of the GEnsat images, 
>> although we haven't gotten very far.  More importantly, BIRN has been 
>> working on exchange of coordinate systems so that different atlases 
>> can talk to each other.
>>
>> I think that's why Bill has been trying to get everyone together on 
>> this. I've added Ilya Zaslavsky, our GIS expert, to this list.
>>
>> Maryann Martone, Ph. D.
>> Professor-in-Residence
>> Dept of Neuroscience
>> University of California, San Diego
>> San Diego CA  92093-0446
>> 858 822 0745 (T)
>> 858 822 0828 (F)
>>
>>
>> On Sat, 3 Mar 2007, William Bug wrote:
>>
>>> Hi Kei,
>>>
>>> You are right on target re: use of a coordinate-based, spatial query 
>>> system to resolve the relatively simple query: "In which brain 
>>> regions is GENE X expressed?"
>>>
>>> This is the whole goal of several major neuroinformatics projects 
>>> currently underway which are designed to use either 2D or 3D digital 
>>> brain atlases to make such a query possible.  Several of those 
>>> efforts are associated with the BIRN project.  In fact several such 
>>> projects working on inbred mouse strain atlases have been striving 
>>> to function synergistically within a single system (the Mouse BIRN 
>>> Atlasing Tool or MBAT) specifically to support such a query. ABA is 
>>> not currently available to query within MBAT, because it's not 
>>> registered to the primary atlas being used in MBAT right now.  This 
>>> work may eventually get done, but it won't be ready for the demo.
>>>
>>> The absolute pre-requisites for resolving such a query are:
>>> 1) you must have a set of canonical brain images (2D) or a true 
>>> voxel based canonical brain (3D) - "ATLASES" - that include 
>>> expert-assisted brain region segmentation.
>>> 2) these canonical pixel-based brain images (2D) or voxel based 
>>> images (3D) must be situated within a defined coordinate space.
>>> 3) the segmented brain regions must be deterministically placed 
>>> within the same coordinate space.
>>> 4) the images containing the gene expression patterns must be 
>>> segmented (manually, semi-automatically, or automatically) to 
>>> provide defined geometries for the expression patterns.
>>> 5) the images containing the gene expression patterns must be 
>>> registered to the canonical atlas data and coordinate space (whether 
>>> 2D or 3D).
>>>
>>> With these conditions met, you could then present a user with a nice 
>>> 3D visualization of the atlas (or even just the list of brain region 
>>> IDs or preferred labels) and/or a list of gene names/IDs and let 
>>> them ask both of the following questions:
>>> a) In which brain regions is GENE X expressed?
>>> b) Which genes does BRAIN REGION X contain defined expression values 
>>> beyond some baseline?
>>>
>>> Right now, GENSAT is not registered to an atlas, so there is no 
>>> coordinate frame to support resolving such as query.  They have 
>>> manually curated many of the gene-specific images with both brain 
>>> regions and cell types, so you can pose that query and get an answer 
>>> based on the curation they have had the resources to do so far, but 
>>> there is no way to place it in a GIS context (2D or 3D), since none 
>>> of their info is YET linked to a canonical coordinate space (several 
>>> projects are working on this very issue).
>>>
>>> ABA has aligned to a 2D mouse brain atlas (F&P C57Bl/6 adult brain 
>>> atlas). In doing so, the 2D brain region segmentations on each of 
>>> the images in the F&P mouse atlas can be super-imposed on the 
>>> registered images from any of the 20,000+ brains.  The problem is 
>>> the current registration has a moderate error associated with it, so 
>>> that answering that query programmatically is problematic and often 
>>> not very informative.  The following can be done:
>>> - along the coronal sectioning axis, give me the plate numbers for 
>>> all the images in the atlas that contain a slice through the STRIATUM
>>> - for ABA brain stained for GENE X, give me all the sections that 
>>> have been roughly aligned to that set of F&P atlas images.
>>>
>>> From there the alignment is so coarse at this point, you could only 
>>> use the atlas plates and location of the STRIATUM to help guide a 
>>> qualitative assessment of whether there appears to be any staining 
>>> in the STRIATUM.
>>>
>>> In fact, via this route, many contributers to GeneNetwork.org have 
>>> actually linked the probe sets in their microarray QTL database to 
>>> staining patterns in ABA.  In other words, if through there system, 
>>> you uncover via QTL a locus or collection of SNPs associated with 
>>> altered expression of a given gene - say Dopamine Receptor, type D2 
>>> (DRD2) - you might find someone has added an ABA or GENSAT 
>>> annotation for DRD2 using the GeneNetwork.org GeneWiki.
>>> 1) Go to www.genenetwork.org <http://www.genenetwork.org>
>>> http://www.genenetwork.org/search3.html
>>> 2) Enter 'DRD2' in the 'ANY' box searching against the default 
>>> settings for other fields - & hit 'Search'
>>> 3) Click on the single result entry
>>> 4) In the record for DRD2, click on the GeneWiki button near the top 
>>> of the page
>>> 5) This will bring up a listing of all the annotations in 
>>> GeneNetwork for DRD2 including qualitative annotations that someone 
>>> did for the ABA DRD2 brain.
>>>
>>> If you want to see ALL of the genes for which ABA or GENSAT GeneWiki 
>>> entries exist, just go back to step '1', enter wiki=ABA or 
>>> wiki=GENSAT respectively in one of the 'ANY' boxes, and hit 
>>> 'Search'.  Then pick up at step '3' above.
>>>
>>> Were we able to SCRAPE this, then you would have annotation for ABA 
>>> that is roughly equivalent to that which exists for GENSAT - ONLY - 
>>> it probably is doesn't cover the ABA very thoroughly (using the 
>>> generic 'wiki=aba' brings up 948 probe sets - or ~5% of ABA - pretty 
>>> remarkable, actually, given its a manual effort), and these GeneWiki 
>>> annotations are mostly in free-text right now and are not done to a 
>>> controlled vocabulary or classification scheme. :-(
>>>
>>> When the registration to the atlas improves to say the 50 - 100 
>>> micron range, then the flood-gates will open, and all 20,000 brains 
>>> in ABA each staining for a particular gene will be able to 
>>> automatically provide relatively solid answers to  these 
>>> straight-forward questions related to where in the brain is Gene X 
>>> expressed - and which genes does Brain Region Y show marked 
>>> expression of.  Even here, however, there will be continued room for 
>>> nuance in defining the ABA staining patterns - AND - there will be a 
>>> need to eventually to add the time dimension to all these queries 
>>> (e.g., "When is Gene X expressed in Brain Region Y?").
>>>
>>> Because the ABA has created multi-resolution versions of their brain 
>>> images (both the Nissl stains for cell bodies and the pseudo-colored 
>>> ISH images for a given gene), it is possible to use the very nice 
>>> Google Maps API GUI Alan created to select a given 1 of the 20,000 
>>> ABA brains and simply Zoom & Pan on the actual pixel image data.  
>>> However, there is no straight-forward way to use it to pose and 
>>> answer SPATIAL queries.
>>>
>>> What MIGHT be possible - based on the alignment they have done and 
>>> the information provided in that brain region ontology Excel file 
>>> Alan has - is to say, for the 'DRD2' brain, filter the sagittal 
>>> image series to create a subset including only those images aligned 
>>> to an F&P atlas images which contains a section through Brain Region 
>>> X (say 'STRIATUM').  This way, if through some SPARQL query you 
>>> pulled up a relation between DRD2 and STRIATUM, you'd be able to 
>>> present a user with a very nice, low-tech interface to quickly 
>>> pan&zoom on the median section of that 'STRIATUM'-filtered series to 
>>> look at the staining pattern.  You could add a navigation control to 
>>> go back-n-forth through the series for the DRD2 brain, so they could 
>>> get a pretty good sense in 3D where DRD2 expression is in the 
>>> striatum.  You might also go to BAMS or CoCoMac (BAMS is better in 
>>> this instance since it's rodent focused - whereas CoCoMac is primate 
>>> focused) to automatically determine what regions connect to 
>>> (is_afferent_to) and what regions are connected to (is_efferent_to) 
>>> the STRIATUM.  You could then bring up another HTML frame that gives 
>>> you a view of the DRD2 subset series for those brain regions, too.
>>>
>>> THAT WOULD ACTUALLY BE A VERY NICE INTERFACE - and is probably quite 
>>> tractable for the demo - if this sounds like a useful feature to 
>>> provide.
>>>
>>> Running atlas-based SPATIAL queries against GENSAT and ABA is a very 
>>> much sought after goal both for the curators of those repositories 
>>> and for the neuroscience community at large, but we are not there yet.
>>>
>>>
>>>
>>> I'm not certain I understand what you are asking re: highly 
>>> expressed genes that correlate with high levels of ADDL or Abeta.  I 
>>> could see how you might be able to use GENSAT (which has a 'staining 
>>> intensity' annotation field) to ask whether genes associated with 
>>> high levels of specific ADDL species or with plaque deposition are 
>>> expressed at high levels in the GENSAT data set - and if so - where 
>>> are they expressed in the brain - and at what developmental time.  
>>> Given the sparse nature of the GENSAT data set, this would not be a 
>>> comprehensive answer to the question, but it could prove very 
>>> interesting. I'm certain June, Gwen, or Elisabeth could help us 
>>> identify genes whose expression correlates with high levels of ADDL 
>>> species (most interesting question given current AD research) or 
>>> with other APP related macromolecules or plaques.  I'm not certain 
>>> how you'd ask the same question of ABA, given there are not 
>>> systematic annotations on staining intensity or pattern - though 
>>> some of this has been done (see below).
>>>
>>> Cheers,
>>> Bill
>>>
>>> On Mar 3, 2007, at 8:01 PM, kc28 wrote:
>>>
>>>> Alan et al.,
>>>> In addition to mapping to brain regions, what seems to be also 
>>>> missing is some kind of brain coordinates. I thought one major 
>>>> advanatage of using Google Map is the ability to issue GIS-like 
>>>> queries. With this type queries, one can potentially query 
>>>> something like finding expressed genes for a given brain region and 
>>>> its neighbouring/adjacent regions.
>>>> While we are talking about gene expression, what seems to be also 
>>>> logical to consider is whether some highly expressed genes 
>>>> correlate with high abundance of pathological proteins (e.g., 
>>>> amyloid beta). Any take from neuroscientists?
>>>> -Kei
>>>> Alan Ruttenberg wrote:
>>>>
>>>>> On Mar 2, 2007, at 1:56 PM, Kei Cheung wrote:
>>>>>
>>>>>> By reading the AD/PD use case, one of the questions has to do 
>>>>>> with  what genes are expressed in what regions of the brain (if 
>>>>>> such gene expressions are localized to certain brain regions). I 
>>>>>> wonder what Alan's currently working on can help address this 
>>>>>> type of question  (even though the kind of gene expression data 
>>>>>> is for the mouse --  perhaps we can find homologous genes for 
>>>>>> human). Also, I'd  encourage people to take look at what Bill 
>>>>>> Bug's Wiki page:
>>>>>
>>>>> What I can do is add an orthology mapping. Probably from orthogene.
>>>>> I can also scrape the Allen site for the following query they provide
>>>>> Brain Region(see list below), 
>>>>> Expression-level(low/high),Expression- density(low/high), 
>>>>> expression pattern(clustered/not clustered). =>  gene set
>>>>> So this would be 16x2x2x2 = 128 different gene sets.
>>>>> There is also their "Fine structure search" :
>>>>> Fine structure annotation lists are genes that have high 
>>>>> specificity expression in particular brain regions or nuclei.
>>>>> They provide these gene lists for a set of structures listed 
>>>>> below  (fine structures).
>>>>> This can lead us to a particular image, though I don't have a way 
>>>>> yet  to identify which portion of the image corresponds to a 
>>>>> particular  region or structure.
>>>>
>>>
>>> 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>
>>>
>>>
>>>
>>>
>
> 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>
>
>
>
>

Received on Monday, 5 March 2007 03:48:33 UTC