Nice summary and comments, Bill. This is the idea of open innovation and open community.

The example I gave includes hypothesis. In addition to the ontologies you mentioned, we might also need to think about the SWAN ontology, which captures hypotheses.

Cheers,

-Kei

Bill Bug wrote:

Hi Susie,

We certainly do need an "Experiment Ontology" - or Ontology of Biomedical Investigation (OBI).

I believe Matthias, Michael, and Kei have all made exactly the points I think are most important to consider:
1) Matthias's comments
Are you following "best practices" in creating the ontology. I believe Matthias gives many instructive examples on how to adjust what is here to bring it much more in sync with the emerging "best practices" that are coming out of the community development surrounding a variety of OBO Foundry ontologies. Matthias also makes the point that its important to seek to re-use (or directly contribute to) the emerging community ontologies to cover the required domains. In the case of this particular Experiment Ontology, the ontologies to consider are Ontology of Biomedical Investigation (OBI), the OBO Relations Ontology, the Gene Ontology (specifically the Molecular Function and Cellular Component branches, the latter of which is designed to capture components down to the level of macromolecular complexes), the Sequence Ontology, Protein Ontology (nascent - but proceeding rapidly), the Cell Ontology - at a minimum. As many on this list know - and I'm certain the talented folks at Lilly who invested time in assembling this ontology also learned - many of these are not fully ready for prime-time, and/or may not FULLY cover the breadth and depth of the domains a specific application requires. However, if one doesn't seek to work with these community efforts, you cannot expect to achieve the ultimately goal, which is to make your data maximally "semantically sticky", so as to ensure the least amount of custom logic and human effort will be required to get the most value from your data. Otherwise, you stand the chance of creating what may be a useful ontology that meets your specific requirements (as has been true of "investigation"-oriented ontologies that have come before such as the MAGE Ontology, ExperiBase, EXPO, myGRID KAVE, etc.), but don't help the community at-large to appropriately re-use your data. In each case, these ontologies or KR frameworks have been extremely useful in the local application context for which they were constructed, but they cannot be effectively employed as the basis for semantically-driven integration across data sets that may not be able to accept the constraints (or lack thereof) of this application-oriented ontology. Would you know off-hand, Susie, whether the folks who worked on this ontology at Lilly have both reviewed the relevant community efforts cited above and/or have sought to interact with those groups to get some input on how best to meet the overall requirements that underlie this particular Experiment Ontology with the minimal required effort and in a manner that could help to ensure Lilly's sunk investment could be of benefit to us all.

2) Michael's comments
It's very helpful to know what the target is when it comes to exporting/exchanging the actual data. As Michael points out, a great deal of work has gone into the production of FuGE (and MaGE before it) to come up with the appropriate division of labor between the semantically-opaque, syntactical requirements as represented in a data model such as MaGE or FuGE and the explicit semantics as captured in the ontology. For those using FuGE, as Michael states, in the realm of syntax, the intention for FuGE is to provide a shared structure for universal elements such as biomaterials, experiment populations/pools/groups, protocol details, reagents details, etc.. Built on that shared, generic foundation, any specific discipline - e.g., microarray expression, GC-MS, FISH, MRI, etc. - can sub-class FuGE components and add what additional detail required in their discipline. In parallel with this effort on data structure, the OBI ontology cooperative seeks to provide that same foundation for the shared semantic domains, and a clear set of recommended practices for how to re-use entities from other OBO Foundry ontologies such as ChEBI, Sequence Ontology, Protein Ontology, OBO Cell, Organism Taxonomy (OWL versions of NCBI Tax), etc. to specify the critical biomedical entities and their complex relations. As I say above, these are works in progress. For those of us who must have something working now, the recommended practice is to actively participate in these projects with an eye toward following their practice - and replacing any "proxy" you create in the interim with the community ontology, when it is ready for use. This is what we have done in the BIRN ontology BIRNLex. We actually have an OWL module called "BIRNLex-OBI-Proxy.owl" which we fully intend to replace with OBI entities, when they are ready for use. We also have "BIRNLex-Investigation.owl" that builds on this "proxy" to cover entities BIRN researchers must capture. We expect to eventually see the contents of "BIRNLex-Investigation" in OBI in some form. We intend to "contribute" those elements from this OWL file directly to OBI, when OBI is ready for them, and we have the time work through this migration process.

3) Kei's comments
Examples - examples - examples. This is critical. Working through the example Kei cites from the NIH Neuroscience Microarray Consortium is a wonderful way to determine whether: - there are existing community ontologies that can meet the KR and processing requirements
- where the gaps are in those community ontologies
- whether the ontology you are creating effectively fills those gaps (if it does, that makes it very clear how the community effort can make effective use of your ontology) In regards to Gene Lists, Kei is certainly correct. If these are captured through algorithmic means, it's critical to capture the details on that algorithm - typically both the version of the algorithm as well as the version of the data repository you ran it against. Also - where gene entities are concerned - there is ongoing work between the GO groups, the Sequence Ontology, and the Protein Ontology that is particularly targeted toward capturing the specific relations between types of genomic sequence elements and types of biologically active protein-based molecules (e.g., macromolecular complexes composed of a collection of proteins in a variety of post-translationally modified states - e.g., GPC receptors, ion channels, transporters, pathway enzymes, etc. - i.e., Rx drug targets). These are the details we'll all require in order to do round-trip pharmacogenetics - i.e.,effects of genetic constructs on target susceptibility to drugs - AND - the ways in which drugs ultimately alter macromolecular complexes by leading to changes in gene expression.

Just my $0.02 filtering on these helpful comments from Matthias, Michael, and Kei.

Cheers,
Bill

On Dec 3, 2007, at 1:00 PM, Kei Cheung wrote:


This is great!

I have a microarray experiment description (that has to do with Alzheimer Disease) extracted from NINDS microarray consortium:

http://arrayconsortium.tgen.org/np2/viewProject.do?action=viewProject&projectId=433773 <http://arrayconsortium.tgen.org/np2/viewProject.do?action=viewProject&projectId=433773>

I just wonder how this example would fit this experiment ontology (as well as others such as OBI) As shown in this example, we record information such as organ type, organ region, cell type (layer II pyramidal neuron), etc. NINDS microarry consortium uses different array platforms (e.g., agilent, Affymetrix, and cDNA) for different organisms so one may need to divide chips into groups corresponding to different platform types. Each group can then be further divided into subgroups corresponding to different organisms.

We also would like to capture gene lists (not the raw gene lists but the ones (much shorter) that indicate what genes are over/under expressed under certain experimental conditions). Such gene lists would usually be extracted from the literature. Also the analysis package (including version) that was used to generate a gene list should be identified. One possible use of these gene lists is to compare them to identify genes are differentially expressed under the same/similar experimental condition across different microarray experiments. This would help identify true signals from noises.

Hope it helps.

Cheers,

-Kei



Matthias Samwald wrote:


Hi Susie,

Susie wrote:

It would be great if you could take a look at it and provide comments. The
ontology is available at:
http://esw.w3.org/topic/HCLSIG_BioRDF_Subgroup/Tasks/Experiment_Ontology


* Some of the entities/properties are missing a rdfs:label or have an empty label (a string with lenght 0). * Some of the entities could be taken from existing ontologies like OBI, RO or some of the OBO Foundry ontologies. This would save work and makes integration with other data sources and ontologies much easier. By the way, there seem to be several groups working on ontologies for mircoarray experiments, or are at least planning to do that. It would be great if these groups could work together. * The class 'Chip type' should be removed and be replaced by subclasses of 'chip', e.g., 'chip (human)', 'chip (mouse)' etc. * Some of the object properties appear like they are intended to be datatype properties (e.g., 'has proteome id'). * Many of the datatype properties could be replaced with object properties, possibly referring to third party ontologies -- of course this would require a richer ontology and more work spent on creating mappings. 'has molecular function' could refer to entities from the gene ontology, 'has associated organ' could refer to an ontology about anatomy and so on. * Object properties and their ranges are quite redundant. Property 'has reagent' has range 'Reagent', property 'has treatment' has range'Treatment' and so on. Maybe the ontology could be designed in such a way that there are only some generic properties such as 'has part'. This would make the ontology much easier to maintain, query and understand in the long term.
* It is unclear how 'Gene list' is intended to be used.
* 'Hardware' and 'Software' should not be subclasses of 'Protocol'.


Many of the datatype properties in this ontology look very interesting and might provide requirements for other ontologies. It would be great if some of them could be described/commented in more detail so that we know more about the requirements that motivated the creation of these properties.

I hope that was somewhat helpful.

cheers,
Matthias Samwald









William Bug, M.S., M.Phil. email: [EMAIL PROTECTED] <mailto:[EMAIL PROTECTED]>
Ontological Engineer (Programmer Analyst III) work: (610) 457-0443
Biomedical Informatics Research Network (BIRN)
and
National Center for Microscopy & Imaging Research (NCMIR)
Dept. of Neuroscience, School of Medicine
University of California, San Diego
9500 Gilman Drive
La Jolla, CA 92093

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