Just another gentle reminder that I'm no longer blogging about science, ontologies, data integration, etc on Vox. I've moved back to The Mind Wobbles at Wordpress.

If you're still here, and not there, then you're missing posts covering the latest FuGE paper describing good design patterns, the publishing of my slides on slideshare (and notes on the blog post) that I used in my last visit to the school I'm partnered with through the Teacher Scientist Network, two posts (1, 2) covering the OBO Foundry Workshop and topics for discussion of the Foundry Principles, and my thoughts on a recent trip to the brand-new Great North Museum.

So, to keep up with my blog posts please visit (and modify your feeds to):

http://themindwobbles.wordpress.com

All of my posts from Vox have been copied across, so there is a complete history over there too.

BBSRC Systems Biology Grantholder Workshop, University of Nottingham, 16 December 2008.

SyMBA Demo. The lunch hour was also the demo hour. People came to visit me at the SyMBA demo desk for the whole hour, and we had some interesting conversations. There is one particular question I would like to relate from that hour: what should a bioinformatician choose as an output/export format for multi-omics data? This post relates my thoughts about this challenge. It's not meant to be comprehensive: just some ramblings.

I solve this challenge in SyMBA by storing everything as FuGE objects, which can be exported to FuGE-ML. FuGE-ML can be converted into ISA-TAB and into an html format that mimics ISA-TAB using an XSLT. Therefore, because of this interlink between FuGE and ISA-TAB, you can leverage two complementary formats.

But to a bioinformatician who has just been tasked with building an application (and generally on a short time-scale), how do they choose what export format to use, e.g. FuGE or ISA-TAB? There are considerations of:

• scale: lightweight or heavyweight implementation. A lightweight implementation might favor your own version of ISACreator and the use of ISA-TAB, or a FuGE-based archive (but not a full-blown LIMS) like SyMBA. A heavyweight solution might be a full LIMS such as PIMS, or another FuGE implementation in development called SysFusion.
• intent: what is the purpose of storing this data? Is it for later analysis? For later deposition to a public database, e.g. at the EBI? Is it archiving? Is it a combination of these things? Your intent will shape what type of application you build, and what formats you focus your effort on. If your intent is storage only, choose whatever is most convenient for your users. However, these days there is always some aspect of data sharing or publishing. If you need further analysis of the data, then you probably want to be able to produce a computationally-friendly format such as XML. If your intent is submission to public databases, you need to ensure you export in a format they import.
  

Unfortunately, what this means is that the decision depends on the circumstances. FuGE and ISA-TAB are linked, and so you really get two for the price of one with those. I see this sort of thing as a positive - you have a choice as to the representation, storage and export of your data - a choice of formats! And many, like FuGE and ISA-TAB, are going to be easily convertable. The choice depends on your needs, but there is one easy choice: use something that's already been developed - don't reinvent the wheel!

Anyone else have any further suggestions?

BBSRC Systems Biology Grantholder Workshop, University of Nottingham, 16 December 2008.

Systems Biology of Microorganisms. 11 projects from 91 institutes, whose aim is to record and describe the dynamic molecular processes occurring in microorganisms in a comprehensive way. These projects have no one concept of experimentation or modelling, which makes it tough for information exchange. Further, there are issues of people having their own solutions, suspicions (about sharing data, for instance), data issues (many don't have data or don't store it in a standard way) and resource issues (no extra resources). SysMO-DB started in July 2008, and is a 3 year funded effort (3+3 people in 3 teams over 3 sites). Provide a web-based solution to exchange, search, and disseminate data. Need to retrofit data access, model handling and data integration platform. Because of the large number of groups and projects, they are going to aim for low-hanging fruit and early wins: be realistic, not reinvent, sustainable, and encourage standards adoption.

Just like at CISBAN, where we have implemented a web-based data integration, storage, exchange, and dissemination platform in a standards-compliant way (SyMBA), they have three users: experimentalists, bioinformaticians, and modellers. They're lucky, though, in that they have 6 people to develop SysMO-DB, when CISBAN only has 1. :) And, as with CISBAN and many other data integration efforts, much of the work is social: that is, encouraging those three user types to collaborate and understand each other's work. The social solutions include questionnairs, "PALS" (postdocs and phd students), and Audits and sharing of methods, data, models. They discuss things like what people need or don't need from MIAME. (Personal opinion and question: MIAME is intended as a minimal information checklist. What kind of things, then, don't they need? And would it be worth taking this information back to the MIAME people to possibly modify the guidelines if some aspects of it aren't truly minimal? End personal questions.)

Discovery is done via SysMo-SEEK. How to catalog the metadata, and then have mechanisms for accessing the data from locations other than the host site? There is a single search point over "yellow pages" and assets catalogue. They store metadata on results, not the results themselves (again, just like SyMBA, which stores the metadata in a database, and the results in a remote file store). They use myExperiment for both linking the people and the assets. For models, they're using a local installation of JWS online, which is a database of curated models and a model simulator. There is also some links to semantic SBML from the TRANSLUCENT project.

There are two kinds of processes to store. The first is experimental processes, e.g. SOPs and protocols. They use the Nature protocols format, with the addition of high-level classification through tags. (Personal note: What is the underlying format for storing protocols?) The second type of process is Bioinformatics processes, which are stored as workflows. (Question: Why don't you store protocols as workflows? They can be chained in the same way.)  Taverna is used for this work. One bit of work was using libSBML inside taverna for collaborative model development (Peter Li et al). Another automated (definition of automated in this context?) workflow goes from microarray to pathways and published abstracts. Their consortium wants to exchange information from public data sources, SysMO itself, and excel spreadsheets.

(Another personal aside. FuGE (object model for experimental metadata) and ISA-TAB (tabular format, e.g. spreadsheets) are becoming interchangeable - work is going on between FuGE and ISA-TAB people right now - most recent workshop was last week. This is important, as it was mentioned that bioinformaticians have to deal with spreadsheets (which is true enough!). So, you get the best of both worlds with FuGE / ISA-TAB, without having to define yet another schema. A personal question would be: Why build these various metadata schemas and parsers for spreadsheets (e.g. whatever is used for the Assets catalogue and JERM parsing of spreadsheets) rather than use pre-existing models such as FuGE and formats such as ISA-TAB? Using the FuGE object model does not mean that you have to use all aspects of it - you can just take what you need.Perhaps it was due to the maturity of ISA-TAB at the time the project started, though the specification is now in version 1.0. Will SysMO-DB export and import these formats? There was no time for questions at the end of the talk, so I will try to find out during the lunch period. End aside.)

Trying to map to the relevant MIBBI standard. There is a nice feature that reads spreadsheets from specific locations and automatically loads them into the Assets catalogue. (You can still load them directly into that catalogue.) They are performing a 4-site JERM exchange pilot scheme in Spring 2009.

Great talk - thanks :)

These are just my notes and are not guaranteed to be correct. Please feel free to let me know about any errors, which are all my fault and not the fault of the speaker. :)

[This post has also been copied across to my researchblogging-friendly wordpress site (now completely defunct except for my research blogging efforts, as Vox doesn't play nicely with their aggregator software)].

Carole Goble and the other authors of "Data curation + process curation = data integration + science" have written a paper on the importance of curating not just the services used in bioinformatics, but also how they are used. Just as more and more biologists are becoming convinced of the importance of storing and annotating their data in a common format, so should bioinformaticians take a little of their own medicine and ensure that the services they produce and use are annotated properly. I personally feel that it is just as important to ensure that in silico work is properly curated as it is in the more traditional, wet-lab biological fields.

They mention a common feature of web services and workflows: namely, that they are generally badly documented. Just as the majority of programmers leave it until the last possible minute to comment their code (if they comment at all!), so also are many web services annotated very sparsely, and not necessarily in a way that is useful to either humans or computers. I remember that my first experience with C code was trying to take over a bunch of code written by a C genius, who had but one flaw: a complete lack of commenting. Yes, I learnt a lot about writing efficient C code from his files, but it took me many hours more than it would have done if there had been comments in there!

They touch briefly on how semantic web services (SWS) could help, e.g. using formats such as OWL-S and SAWSDL. I recently read an article in the Journal of Biomedical Informatics (Garcia-Sanchez et al. 2008, citation at the end of the paper) that had a good introduction to both semantic web services and, to a lesser extent, multi-agent systems that could autonomously interact with such services. While the Goble et al. paper did not go into as much detail as the Garcia-Sanchez paper did on this point, it was nice to learn a little more about what was going on in the bioinformatics word with respect to SWS.

Their summary of the pitfalls to be aware of due to the lack of curated processes was good, as was their review of currently-existing catalogues and workflow and WS aggregators. The term "Web 2.0" was used, in my opinion correctly, but I was once again left with the feeling that I haven't seen a good definition of what Web 2.0 is. I must hear it talked about every day, and haven't come across any better definition than Tim O'Reilly's. Does anyone reading this want to share their "favorite" definition? This isn't a failing of this paper - more of my own lack of understanding. It's a bit like trying to define "gene" (this is my favorite) or "systems biology" succinctly and in a way that pleases most people - it's a very difficult undertaking! Another thing I would have liked to have seen in this paper, but which probably wasn't suitable for the granularity level at which this paper was written, is a description and short analysis of the traffic and usage stats for myExperiment. Not a big deal - I'm just curious.

As with anything in standards development, even though there are proposed minimal information guidelines for web services out there (see MIAOWS), the main problem will always be lack of uptake and getting a critical mass (also important in community curation efforts, by the way). In my opinion, a more important consideration for this point is that getting a MIA* guideline to be followed does not guarantee any standard format. All it guarantees is a minimal amount of information to be provided.

They announce the BioCatalogue in the discussion section of this paper, which seems to be a welcome addition to the attempts to get people to annotate and curate their services in a standard way, and store them in a single location. It isn't up and running yet, but is described in the paper as a web interface to more easily allow people to annotate their WSDL files, whereas previous efforts have mainly focused on the registry aspects. Further information can be associated with these files once they are uploaded to the website. However, I do have some questions about this service. What format is the further information (ontology terms, mappings) stored in? Are the ontology terms somehow put back into the WSDL file? How will information about the running of a WS or workflow be stored, if at all? Does it use a SWS format? I would like to see performances of Bioinformatics workflows stored publicly, just as performances of biological workflows (eg running a microarray experiment) can be. But I suppose many of these questions would be answered once BioCatalogue is in a state suitable for publishing on its own.

In keeping with this idea of storing the applications of in silico protocols and software in a standard format, I'd like to mention one syntax standard that might be of use in storing both descriptions of services and their implementation in specific in silico experiments: FuGE. While it does not currently have the structures required to implement everything mentioned in this paper (such as operational capability and usage/popularity scores) in a completely explicit way, many of the other metadata items that this paper suggests can already be stored within the FuGE object model (e.g. provenance, curation provenance, and functional capability). Further, FuGE is built as a model that can easily be extended. There is no reason why we cannot, for example, build a variety of Web services protocols and software within the FuGE structure. One downside of this method would be that information would be stored in the FuGE objects (e.g. a FuGE database or XML file) and not in the WSDL or Taverna workflow file. Further, there is no way to "execute" FuGE XML files, as there is with taverna files or WSs. However, if your in silico experiment is stored in FuGE, you immediately have your computational data stored in a format that can also store all of the wet-lab information, protocols, and applications of the protocols. The integration of your analyses with your wet-lab metadata would be immediate.

In conclusion, this paper presents a summary of a vital area of bioinformatics research: how, in order to aid data integration, it is imperative that we annotate not just wet-lab data and how they were generated, but also our in silico data and how they were generated. Imagine storing your web services in BioCatalogue and then sharing your entire experimental workflows, data and metadata with other bioinformaticians quickly and easily (perhaps using FuGE to integrate in silico analyses with wet-lab metadata, producing a full experimental metadata file that stores all the work of an experiment from test tube to final analysis).

Goble C, Stevens R, Hull D, Wolstencroft K, Lopez R. (2008). Data curation + process curation=data integration + science. Briefings in bioinformatics DOI: 19060304

F GARCIASANCHEZ, J FERNANDEZBREIS, R VALENCIAGARCIA, J GOMEZ, R MARTINEZBEJAR (2008). Combining Semantic Web technologies with Multi-Agent Systems for integrated access to biological resources Journal of Biomedical Informatics, 41 (5), 848-859 DOI: 10.1016/j.jbi.2008.05.007 

Tomorrow is the first day of a two-day workshop set up to continue the integration process between the ISA-TAB format and the FuGE standard. (Well, technically, it starts tonight with a workshop dinner, where I'll get to catch up with the people in the workshop, many of whom I haven't seen since the MGED 11 meeting in Italy this past summer. Should be fun!)

ISA-TAB can be seen as the next generation of MAGE-TAB, a very popular format with biologists who need to get their data and metadata into a common format acceptable by public repositories such as ArrayExpress. ISA-TAB goes one step further, and does for tabular formats what FuGE does for object models and XML formats: that is, it is able to represent multi-omics experiments rather than just the transcriptomics experiments of MAGE-TAB. I encourage you to find out more about both FuGE and ISA-TAB by looking at their respective project pages. The FuGE group also has a very nice introduction to the model in their Nature Biotechnology article.

Each day I'll provide a summary of what's gone on at the workshop, which centers around the current status of both ISA-TAB and some relevant FuGE extensions, as well as the production of a seamless conversion from FuGE-ML to ISA-TAB and back again. ISA-TAB necessarily cannot handle as much detail as the FuGE model can (being limited by the tabular format), and therefore in the FuGE-ML to ISA-TAB direction, it is possible that it may not be entirely lossless. However, this workshop and all the work that's gone on around it aims to reconcile the two formats as much as possible. And, even though I have mentioned a caveat or two, this reconciliation is entirely possible: both ISA-TAB and FuGE share the same high-level structures. Indeed, ISA-TAB was created with FuGE in mind, to ensure that such a useful undertaking used all it could of the FuGE Object Model. It is important to remember that FuGE is an abstract model which can be converted into many formats, including XML. Because it is an abstract model, many projects can make use of its structures while maintaing whatever concrete format they wish.

Specific topics of the workshop include:

• Advance and possibly finalize XSLT rendering of FUGE Documents into ISA-TAB. This includes the finishing-off of the generic FuGE XSL stylesheet.
• Work on some of the extensions, including FCM, Gel-ML, and MAGE2. MAGE2 is the most interesting for me for this workshop, as I've heard that it's almost complete. This is the XML format that is a direct extension of the FuGE model, and will be very useful for bioinformaticians wishing to store, share and search their transcriptomics data using a multi-omics standard like FuGE.
  

Thanks to Philippe Rocca-Serra and Susanna-Assunta Sansone for the hard work they've done on the format specification, and for everyone who's coming today. It's a deliberately small group so that we can spend our time in technical discussion rather than in presentations. I'm a bit of a nut about data and metadata standards (and am in complete agreement with Frank over at peanutbutter on the triumverate of experimental standards) and so I love these types of meetings. It's going to be fun, and I'll keep you updated!

Susanna-Assunta Sansone / Philippe Rocca-Serra
Afternoon Session, 2 September (11th MGED Meeting, 1-4 September, 2008)

Standards are a means to an end: they are meant to provide an unambiguous representation, description, and communication of data and metadata. They allow interoperability of resources and advance science, and facilitate data integration.

There is a proliferation of standarization efforts, which can be subdivided into three main categories: Syntax (FuGE, ISA_TAB), Content (checklists, e.g. MIAME), and Semantics (OBI). There are both standards developing organizations as well as grass-roots movements. However, what tends to happen is that a particular community is focused on their needs, which can lead to duplication of effort. This is normal, but the natural progression is a shared, integrated standard.

One example of fragmentation is as follows: within the EBI, MGED required submission to ArrayExpress, and HUPO-PSI required the same for PRIDE. However, each had their own interface and toolset, which makes things difficult when you have both types of data - they're not interoperable.

So, how can we move on? There is a growing complexity in the datasets, and a move towards systems biology. We make use of the synergistic integrative standards.

Integrative Content Efforts: The MIBBI project contains the  list of other people trying to define minimum content, and using these aims to ensure orthologous work. Also, the OBO Foundry aims to allow new ontologies to be created in an orthologous way. Also, publishing an open ontology should be analogous to publishing an open-access scientific paper, in many respects.

Integrative Semantics Efforts: OBI.

Integrative Syntactic Efforts: FuGE, ISA-TAB. FuGE is an extensible framework for describing life-science experiments. ISA-TAB is similar to both FuGE and MAGE-TAB. It is a bit like a tabular format of FuGE, and it is an upgrade of MAGE-TAB that works for other omics data types. It is completely backwords-compatible with MAGE-TAB.

The BioInvestigation Index, being developed at the EBI, will use many of these.

These are just my notes and are not guaranteed to be correct. Please feel free to let me know about any errors, which are all my fault and not the fault of the speaker. :)

Chris Stoeckert
Afternoon Session, 2 September (11th MGED Meeting, 1-4 September, 2008)

How do we tie together the various "silos" of communities and data? There is a real ecosystem of biomedical standards. Not just MGED, but also PSI, MSI, OBO, BIRN, etc. Each community generates its own list of acronyms etc :)

We need to bring community standards together into a single, common, integrative standards. MGED is working on MIBBI, FuGE, ISA-TAB, OBI, and MINSEQE. But having standards is only the first step: we need tools to make use of these standards.

MINSEQE is to help prepare for datasets based on UHTS related to research typically done with microarrays. There is crossover with communities primarily concerned with sequence data (e.g. GSC), and existing formats such as SRF. Where should such data get deposited?

Examples of an ultra-high-throughput (UHTS) experiment: chromatin modifications from normal versus disease cells, meta-genomic analysis of a microbial culture. UHTS requires standardization at multiple levels: from sequence reads to interpreting results.

These are just my notes and are not guaranteed to be correct. Please feel free to let me know about any errors, which are all my fault and not the fault of the speaker. :)

The two-day FuGE Users' workshop was organized by Norman Paton and held at the University of Manchester. It was great fun, and if you just want the short summary of my time there, then just know that there was loads of enthusiasm for FuGE as well as interesting talks, both by communities who were already extending FuGE, and by  developers who were already building tools and databases based on it. There were only a dozen or so people, which kept the discussions lively but neither too long nor too divergent. The workshop dinner was great, though the trip to the restaurant was correctly described by one of the attendees as an Odyssey. For more information on the social aspect of the FuGE workshop, please have a look at Phil Lord's humorous posting on the matter. For another post on the workshop, see the peanutbutter Bioinformatics blog by Frank Gibson.

If you wish to read the longer notes rather than the short summary, then please read on!

Please note that these are my own notes, and are in no way considered to be an "official" FuGE report on the workshop. As such, any errors or inconsistencies are entirely my own. However, if you see a problem with this post, then please let me know, and I'll fix it!

The objectives of the workshop were to share and document experiences in the use of FuGE, to identify good-practices, to document guidelines, and to make known these experiences and guidelines. Hopefully, the result will be a paper that documents the current users' experiences and increases communities' understanding of FuGE. It will hopefully help people who who have read the Nature Biotechnology paper and want to use FuGE, but aren't completely sure what to do next.

Attendees were:

Peter Wilkinson, from Montreal, who was interested in FuGE for flow cytometry.

Khalid Belhajjame: works with Norman Paton in Manchester, and who may soon be a full-time developer of FuGE

Javier Santoyo: University of Edinburgh, part of a consortium trying to develop standards for RNAi work

Andy Jones: one of the original developers of FuGE, from Liverpool, developed GelML with Frank Gibson.

Heiko Rosenfelder: German Cancer Centre at Heidelberg, here as part of MIACA, and wants to use FuGE for the cellular assay format.

Martin Eisenacher: Proteome Centre (mzML and analysisXML) and wants to use FuGE

Phil Lord, Frank Gibson: via CARMEN, wants to use FuGE. Frank also developed GelML with Andy Jones.

Neil Wipat, Matt Pocock, Allyson Lister: We use FuGE in our internal application for storing HT data. Matt and Allyson also involved in OBI.

Leandro Hermida: SIB, they're part of a group that is making SystemsX. Want to use FuGE to store and manage the data. Also want to make an extension of FuGE for deep sequencing technologies.

Norman Paton: originally from proteomics field, but developer of FuGE and organizer of the workshop.

Session 1: Experiences Using and Extending FuGE

GelML – Frank Gibson and Andy Jones

GelML is a FuGE extension that has passed the PSI approval process. PSI defines community standards for data representation in proteomics. There are a variety of working groups, including gel electrophoresis, mass spectrometry, protein modifications, etc. Within the Gel WG there are three specifications: MIAPE-GE (minimum checklist for reporting gel elecrotphoresis experiments), sepCV (controlled vocabulary), and GelML (data transfer format, based on FuGE).

GelML covers the model of a gel, 1-D and 2-D GE, other (N-dimensional) GE's, sample loading, electrophoresis, detection, image acquisition, the excision of locations on gels, and SubstanceMixtureProtocol and SubstanceAction.

The first extended FuGE class described was the Material abstract class. The first of such classes is the Gel class. A Gel has Dimensions, MeasuredMaterial, and others. You use the “Measurement” package to describe the characteristics of the Gel. Measurements include PercentageAcrylamide, while information about the gel (i.e. if purchased, from where), information on the Dimensional Units and CrossLinkerRatio are all FuGE OntologyTerms). MeasuredMaterial was not originally in FuGE because it was planned that such substances could be captured by ontology terms. Rather than using named associations to GenericParameter, they tended to use either GenericParameter (with a CV term) or extended the Parameter class. This was just a design decision, and he would like to see how others do it.

Another extended FuGE class is the Protocol abstract class. The GelML SampleLoadingProtocol has an AddBufferAction which points to a SubstanceMixtureProtocol. 2DGelProtocol has a SampleLoadingAction, a FirstDimensionAction, a SecondDimensionAction (both Electrophoresis protocols), and an InterDimensionAction (for when something happens between the first and second dimension actions), and the DetectionAction.

Within the Electrophoresis protocols there is the ElectrophoresisStop (an Action) which contains a StopTime, which is a TimeParameter, with has Duration and TimePoint. They'd be really interested to see how others have/would like to model time.

It was also a design decision to guide people with the structure of the XML to help them know what to fill out, e.g. you must have a 2dGelProtocol.

For each case, should we extend the FuGE model or add experiment-specific semantics through the use of ontologies? I think this is a case of using both, depending on the circumstances.

They have used standard XML references within the documents. But, for instance, do we still need internal document identifiers when the ontologyURI is a globally-unique identifer anyway? Maybe required if the terms are created ad hoc within the group making the XML file. What is the best way to use ontologies?

AnalysisXML – Martin Eisenacher

http://www.fp6-prodac.eu

He is a member of the ProDaC Consortium. ProDaC is a funded consortium that is meant as a “coordination action” within the 6^th EU Framework Programme. Its aims are the development of international standards, standardized data submission pipelines, systematic data collection in public standards-compliant repositories, and data access for community and publication. There was a kick-off meeting of ProDaC in Long Beach in October 2006, and there have been two workshops since.

Proteomics data includes spectra (peak lists), and peptide lists. He works specifically with the MS (for peak lists and instruments, mzML) and Proteomics Informatics (for “results”, analysisXML) PSI WG's. mzML is a merger of mzData and mzXML. Perhaps this merger is one of the reasons that it is not currently FuGE-based. AnalysisXML includes annotation of search databases, search, algorithms, search parameters, instrument characteristics, peptides (peptide-spectrum link, peptide scores), proteins (protein-peptide link, protein scores, significance values, false-discovery estimation) and quantisation. In September 2007 they added comments into the UML that are passed into the XML.

They use the MagicDraw Community Edition, which is available for free. The Analysis package is subdivided into process, quantisation, and search. Process contains things that aren't directly related to the search protocol applications, but other steps such as ProteinDetermination and PolypeptideProcess. Some of the classes they have made that inherit from the Data class inside the search package include AnalysisResultSet (a set of spectra), AnalysisResult (a spectrum), and AnalysisResultItem (all peptides found for that spectrum). These are all abstract classes, whose concrete subclasses include PolypeptideResultSet, PolypeptideSearchResult, and PolypeptideResultItem.

At the moment they are assembling their own CV (to include search parameters that are most commonly used in search engines like MASCOT), but they can also use Pride CV. They use the ontology classes directly from FuGE, without extending it. This means that it fits what they need without modifications.

In analysisXML, peptides and sequences are listed only once. Different types of analyses in one file or in separate files with external cross-references. Also, the AnalysisProtocol could be used as parameter input for search engines. However, there are many cross-references and unique identifiers that are not validated by the FuGE Schema. Further, there are external cross-references to mzML, which can be difficult if you have only local files and not public URI's. Also, sequences (just the letters) are not polypeptides (“real” molecules with modifications). Therefore, the ConceptualMolecule FuGE class is not appropriate for polypeptides, though it is suitable for sequences (though they are still able to use that class). Additionally, the ResultSet-ResultItem hierarchy does not fit all analysis types. Finally, many FuGE elements seem to have very long names that aren't always useful (but you shouldn't be typing XML manually!).

All items of the collections have unique identifiers. References to them are attributes called “..._ref”. Schema validation does not consider whether _ref links to an allowed section (or that used CV's are allowed). In mzML, for example, “semantic validation” of CV's is possible (suggested/implemented by the EBI). Are identifier checks possible? ProDaC has an online validator for mzML, analysisXML, mzData and prideXML that performs semantic validation, though the extra ontology/CV checks are only supported for mzML.

Still to do is the finalization of analysisXML, which is a deliverable for last October! They also want to provide “Quality Determination” as a process. They also want to make some use-cases and instance documents. They will have some from Matrix Science, MPC. Also, they need to finalize the CV they are using.

SyMBA – Allyson Lister

I gave this talk, so I didn't write anything about it! Instead, have a look at the SourceForge website (http://symba.sf.net):

The Integrative Bioinformatics Group, headed by Neil Wipat and part of The Centre for Integrated Systems Biology of Ageing and Nutrition (CISBAN), has developed a data archive and integrator (SyMBA) based on Milestone 3 of the Functional Genomics Experiment (FuGE) Object Model (FuGE-OM), and which archives, stores, and retrieves raw high-throughput data. Until now, few published systems have successfully integrated multiple omics data types and information about experiments in a single database. SyMBA is the first published implementation of FuGE that includes a database back-end, expert and standard interfaces, and a Life Science Identifier (LSID) Resolution and Assigning service to identify objects and provide programmatic access to the database. Having a central data repository prevents deletion, loss, or accidental modification of primary data, while giving convenient access to the data for publication and analysis. It also provides a central location for storage of metadata for the high-throughput data sets, and will facilitate subsequent data integration strategies.

Developing Flow Cytometry FuGE extensions – Peter Wilkinson

Developing MIFlowCyt. Originally, they stored the metadata and data in a single file, but their latest format (ACS) will separate these two types. They are considering having some of their data formats be in RDF as well as XML, even for those formats that will be built on FuGE – is there a good XML to RDF converter? I suppose so, as I've been able to save OWL/RDF as OWL/XML in Protege 4.

One example of their extension is Cytometer, which is a subclass of equipment. How descriptive should they get with their samples? Should it be at the entity or attribute level? For instance, there is a conceptual difference between prepared samples and “generic” materials. But why not draw an association to material and call it “sample”? They can't do that because sample has a lot of associations itself that aren't present in Material. For things like buffers and solutions, spML doesn't seem to view them as things that exist – you just talk about them in the protocol. This way you don't have to list them 1000s of times. In FC, you have to know exactly which thing is used in the protocol (e.g. they must record batch numbers). However, you could have a single buffer instance, and then in the ProtocolApplication you have a specific parameter that is modified in that particular application of the Protocol, such as the batch number.

Open issues include: FuGE should reference a stable version of AndroMDA, there should be a best-practice for deciding when a Generic* class is replaced by a specific omics-type class, how is the OntologyTerm abstract class intended to be used for specific controlled lists, fitting the organism into FuGE::Bio somewhere, and versioning.

He's also trying to write a FuGE database by hand, rather than using what is generated by AndroMDA, as he needs to squeeze as much performance out of the system as he can. Much more difficult, but could conceivably be much more efficient.

Generic and Custom Extensions – Andy Jones

spML is for sample processing. SubstanceMixtureProtocol is for describing a mixture of substances, e.g. buffers and solutions and the method of their creation. Actions relate to constituents. Timings relate to constituents and volume, concentration, or mass. SetPropertyAction is a generic model to be used in conjunction with protocols where parameters may be set with associated ActionText. Their chromatography extension comprises extensions of Protocol, Equipment, and ProtocolApplication. The ChromatographyProtocol contains extensions of Parameter, has a child protocol for sample injection, and various uses of GenericActions. With ChromatographyEquipment, there is column-associated sub-components. All extensions of Chromatography equipment can have additional parameters, including specific named parameters where they are always required. Uses Equipment:make. The mobile phase of LCProtocol is described using the SubstanceMixtureProtocol. Inputs are defined with GenericMaterialMeasurement, and the outputs are either Chromatogram (ExternalData) and SeparationFraction. You can also have two-dimensional chromatography.

GenericSeparation is a protocol that uses generic models for defining substance used to create a separation gradient and the parameters applied. In this case, the equipment defines the type of separation and criteria using ontology terms – but how do you communicate how this should be used to all of the developers? In contrast, we don't want to have huge models. Inputs also defined using GenericMaterialMeasurement, and the outputs are either SeparationLog (ExternalData) and SeparationFraction.

TreatmentProtocol is a simple model for treatments, intended for labelling, mixing, splitting, and washing, for example. The treatment IO in TreatmentProtocolApplication is restricted to having material inputs and material outputs only.

There seems to be three sorts of models: column-oriented, category-oriented, and completely generic protocols. Much of what is in spML might be useful for the “library of models” we've been discussing.

The generic model is very flexible for different types of separation, and could be used for LC, GC, capillary electrophoresis, rotofors etc. It is also unlikely to break if new type of experiment is defined, and the Treatments model could potentially be useful in the context of any experiment type. Also, the generic model is much smaller, and can be used in various ways. However, this last one could be a “con” as well, because different users/implementers are likely to encode the same information in different ways. Further, a specific model can guide the user to provide specific details, e.g. for MIAPE compliance.

spML units are derived from the OBO Unit Ontology. Should FuGE extensions be allowed to have user-defined terms? It would be useful for the creation of in-house lists to populate drop-down menus.

Issues

spML units Below are a list of questions and suggestions that we came up with while the initial talks progressed in the first couple of sessions. Many were discussed, and some were answered, in breakout sessions later. Notes from the discussions I was a part of are included below. The unanswered points in the list may have been discussed at other breakout sessions, or may still be untouched.

Discussion on Semantic Validation and Identifiers: Khalid Belhajjame, Norman Paton, Allyson Lister, Martin Eisenacher

Identifiers and Auxillary/Semantic Validation: Types of Validation and How Simple Support can be done.

	Unique in Document		Not Dangling		Globally Unique		Type Correct		Notes
	Property	Checked by XML Tooling	Property	Checked by XML Tooling	Property	Checked by XML Tooling	Property	Checked by XML Tooling
Instances of Identifiable	yes	GP	yes	GP (yes?)	(+)	no	yes	no	See (1)
Ontology Terms	(#)	n/a	yes	no	yes	no	yes (not in UML)	no (^)
External Data	($)	n/a	yes	no	yes	no	yes	(*)	(*)want to know it's a file of a particular kind

GP: Can be checked with a generic program.

All things marked GP or X could be attacked by people wanting to write a semantic validation tool.

(+) Only for some types of Globally-unique identifiers would we be able to check that they were truly unique and well-formed.

(#): Should OntologyTerm elements be unique (irrespective of their identifiers, which must be unique)? If people compare OT identifiers they may think two terms are different when in fact they are the same, and someone was sloppy when making OT elements. However, if they have linked their OT to an OntologySource then it can be checked if it is both unique in document and globally unique (if it is a logical/physical uri)? In that case, why should OS be optional at all, if custom CV's can be included in the OS.

(^): This is where the ontology mapping files come in.

($): The same argument for uniqueness of ED applies as that in OT.

(1) Will we suggest a type of identifier to use with FuGE as a best-practice?

Do we still need internal document identifiers when the ontologyURI is a globally-unique identifier anyway?

Should identifiers be human readable?

Do community extensions automatically have their own namespace/prefix? That is, if “sample” is used in the FC community and also in another extension, will it be problematic if you try to create a multi-omics FuGE-ML file? This is all about linkage between different FuGE-based instances (unique identifiers, both within a single document and between documents.What is the identifier an identifier of? Is every Identifiable object a “first-class citizen”? We shouldn't force all (any!) identifiers to be URI's.

Should you use a logical or physical naming scheme?

• Physical naming schemes:

  • Are fragile

  • May not work for all users (i.e. if the URI points to a laptop that isn't publicly accessible)

• Logical naming schemes:

  • Are robust, but require a greater investment of time, as they need tools that provide resolving facilities.

• If locally-unique identifiers are used:

  • it means that you may get into trouble in the long run

• If globally-unique identifiers are used:

  • clashes between different FuGE-ML files will be avoided

• People should look this over and discover which is the best setup for their situation.

If we use URI's, should URI's be resolvable? What is the scope?

• Martin has a URI that points to a data file, and a (possibly locally unique) identifier that points to a spectrum within the data file. How to deal with this? Do we have a best-practice for it?

Schema Validation

• Schema validation does not consider whether _ref links to an allowed section (or that used CV's are allowed). Native XML validation does not do this, but you could make a tool. In theory, the prefix before the _ref is always the name of the class. FuGE needs semantic validation.

• How should user-defined ontology terms be validated in the XML?

Discussion on Versioning: Khalid Belhajjame, Norman Paton, Allyson Lister, Phil Lord, Matt Pocock, Leandro Hermida

• Is there a best way to implement versioning?

Characteristics of (SyMBA) Versioning:

1. Complete History of Atomic Changes

2. Low Cost of Updates – No Cascades

3. Higher Cost of Retrieval

This is actually a transaction-time database with tuple-level timestamps. In a transaction-time database, the time is in the world of the database and not the time in the real world (vs valid-time database, where the time you insert does not match the time that you actually wanted to input). If you don't put the timestamp in the tuple, you put it in the attribute. In this context, people have looked at the properties of update operations.

Can't just use LSID versioning because there is no specification of how the version should be updated.

SyMBA Versioning Requirements:

1. Preserving the semantics of the LSID

2. Getting exactly the version requested, and getting all versions

3. Nothing should disappear

This isn't necessarily versioning, or what versioning in FuGE should be.

Leandro's Versioning Requirements:

1. Getting exactly the version requested, and getting all versions
   
2. Nothing should disappear
   

Should this be done in FuGE, or in the FuGE-OM specifically? Perhaps just in the Maven build? We could put hooks in FuGE that would allow fine-grained logging. The current Audit setup does not allow linking back to previous versions unless you put the delta in free text somehow. The Audit classes may be suitable for XML, and you could make a log of such changes and roll-back (in a non-RDBMS way) to whatever version you want.

While it is clear we could make an STK that could have versioning of some type, whether or not this should be a (optionally-used) change to the OM is a much bigger thing. It is certainly a worry that versioning has to be dealt with at the application level. However, versioning at the file or XML level means multiple files, otherwise you'd have to apply a diff to a very large file.

We haven't really had the time to scan the space of options here. We could circulate a general document, and then outline what's actually been done so far. A paper would, in any case, be centered around pros/cons, and a bit less on current implementations, but definitely not say which is the “right” way to do things, as there is no single right way.

There are different technical solutions, and not all of these solutions should necessarily be provided in the model.

Discussion on Tools – Leandro Hermida, Heiko Rosenfelder, Neil Wipat, Phil Lord, Allyson Lister

• What about trying to get some automatic mapping between the XML classes and the Hibernate/Spring classes?

  • There is a disconnect between the XSD that is generated from the XML schema cartridge and the code generated from your persistence cartridge.

  • This means you have to write your mapping manually.

  • There is a possibility that we could get hyperjaxb3 to work for this (Allyson had tried with an earlier version but it didn't work properly). Hyperjaxb3 generates both Entity POJO's and the jaxb2 classes. So, in theory you could only use the Andromda XSD cartridge and hyperjaxb3 for the rest. However, then you loose all the information that is present in the UML but not in the XSD.

  • Hyperjaxb3 uses both hibernate and ejb3 natively (you can choose). Leandro wants to work on a merged persistence/hyperjaxb3 extended cartridge, or perhaps its own cartridge. So perhaps the generation of a hyperjaxb3 cartridge.

• Is there an XSLT that could be made to have a “standard” way of viewing a fuge experiment?

  • Khalid mentioned that it is important to allow input from the programmer in such a tool, so they can see as little or as much of the FuGE structure as you wish to present to the user.

  • Leandro is working on an ejb3 cartridge from the androMDA plugins project (not part of the AndroMDA core yet), and have used FuGE as a test-case. What this cartridge does is generate a mapping file and load it into any application server running hibernate and it will generate your database. Whereas the Hibernate+Spring cartridge generates 1) Entity POJO's + mapping files 2) Spring DAO + DAOException + DAOImpl. With the ejb3 cartridge you get 1) ejb3-annotated Entity POJO's + DAO*.
    You can use Spring, if you wish, to build your web framework. Leandro decided to instead use Seam, which is the business layer of a web framework that builds on top of ejb3. Seam then uses the JSF (Facelets) and Jboss RichFaces for the actual web UI.
    To get the Seam classes, you model <> classes and then draw dependencies, which then auto-generate Seam-enabled ejb service beans. However, the Facelets and RichFaces have their xhtml files manually, though AndroMDA creates the entire web/ structure and base Seam classes for you.
    This doesn't answer our simple UI question.
    The ejb3 cartridge has a web service (jax-ws, via soap) to your DAO's and Entity POJO's.

  • With MAGE, someone wrote a regular Java Swing program where you download the jar which opens a little tabbed client that views MAGE. We could do something similar. (A J2SE app to write/read FuGE-ML of nice wizard interface)

  • The GSC has a lightweight XSD-to-web-form software app.

  • An XSLT, which is a style-sheet that is richer than CSS, but it is a tough language to use (convert XML to “HTML”). XSLT's don't have first-class functions, so you can't do anything generic.

  • Also would like to have simple jar that has input XML, output HTML.

  • This means three tool types here: 1) heavyweight (already existing in SyMBA and SystemsX) 2) midweight (J2SE app to read/write with a wizard-like interface) 3) lightweight (input XML, output HTML with some simple options).

• Tool support for FuGE STK version 1, including a validator.

  • The MAGE STK includes a validator.

  • XML validation can be done with JAXB2 as is with the Milestone 3 STK, but longer-term we need the semantic validation tool.

  • Perhaps have some ontology lookup helper classes (OLS from the EBI?) to help users and developers add terms from (a certain set of?) ontologies. This may help people populate their databases, choose a term from a list on a front-end tool, etc.

• Tool support for database schema / AndroMDA / Alternatives.

  • Dealt with in the other sections

Discussion on Challenging Constructs, including Investigation Package, Abstract Associations, and the Ontology Package - the entire group

• What is the real meaning of the Investigation package? It's one of the few parts of FuGE that isn't meant to be extended.

• How is the OntologyTerm abstract class intended to be used for specific controlled lists? One example is taxonomies as opposed to ontologies.

The intention is that this package would not be changed or extended by communities. Each technology would be reported in the InvestigationComponent. The Factor class actually is meant as a summary report of the factors used in the experiment. There is currently no direct link between the Factors and the protocol workflows – the detail can be recorded in other places in FuGE. It's a summary and duplication of the factor information.

So, if you want to say that your Investigation compared two different values for a single factor, the Investigation has the factor type, but not the data for the factor or the values themselves. However, you can connect to the data made from the various omics technologies via the DataPartition class. There could be a problem where it is a set of factors that only together make a particular set of data useful. Example: if your important aggregate of factors is time1.mouse1.foodstuff1. However, you would have to have each of these factors would be named separately, and you would get a different slice of data for the time1 than you would for the mouse1. How to you join them up? Perhaps allow multiple FactorValues (and OntologyTerms) for a single Factor. Not a very nice solution, though. Perhaps you don't need to change it at all, as you would only add Factors that are relevant to a particular InvestigationComponent. How do you describe which combinations of Factors are the combinations you're interested in? Norman did this by seeing an IC as a particular run of an experiment.

Dimensions are used in FuGE as a way of naming coordinates in a matrix. This does not mean that the data has to be stored here. You can store the data internally via the InternalData class, or you can reference it externally via the ExternalData class (or, of course, create your own subclass of Data).

There are 21 <>'s in FuGE, and all but 6 have identical concrete associations. Some auto-generated AndroMDA code mistakenly ignores the “abstract” parts and incorrectly generates the methods etc. In this case, you can just delete the abstract association in your copy of the UML and re-generate the code. It should be fixed within AndroMDA, though.

For multi-dimensional data, DataPartition are meant as a mechanism to relate back to the data from the Investigation, but many groups will choose not to use DataPartition. Very big, regularly-shaped data sets will be good things to use DataPartition with (e.g. Flow Cytometry). In the case of proteomics data, this may be more of a challenge. A best-practices documents should contain information on which data types are best-suited to this system, and which aren't. It should also include any alternatives to this system. One alternative solution to using DataPartition and its associated coordination system for dimensional data is to build an association from their data of interest back to FactorValue.

What is PartitionPair? In the case where you have two data files, and you wish to associate a particular row of one data file (for example) to a particular spectrum in another (to continue the example). So, it is a “shortcut” to linking particular data sets.

How should users of FuGE build CV lists using the Ontology Package? An OntologyTerm has an OntologyProperty, which contains both a DataProperty and ObjectProperty (these are the relationships within an ontology). Also inside OntologyTerm is OntologyIndividual. OI is the individual itself. Why not just provide the term – why try to recreate the structure of an ontology into UML? However, in OWL, every single class, relationship etc has a URI, so why not use those in UML? An example use: you have in an ontology the concept of age, which has an initial time point and a unit. How do you pull that concept into the UML? We're essentially creating a cut-down version of the ontology to allow extensibility in FuGE. But why would you want this? To create an individual of an ontology within the UML. It also allows restrictions of the name-values (left and right-hand side of a relationships) to those that are allowed within the ontology. One opinion is that there shouldn't be a purpose-built extensibility point in UML, as the entire purpose of UML is that it is extensible everywhere. It also means that users of your FuGE file don't need to parse both that file and the ontology file. However, the users of your file must understand your extensibility point that you've made, which isn't useful. The extra knowledge should be stored in that ontology, in the same way as analysisXML links to mzML. One solution is to have a Property class with term “height” and a Value class with term “meters”, and a PV class with associations to both Property and Value that provides the link. In the end, this is optional. In the guidelines, these concerns should be expressed.

Other questions not fully addressed:

• How do we find out when Generic* classes should be replaced by a specific omics-type class? Rather than using named associations to GenericParameter, GelML tended to use either GenericParameter (with a CV term) or extended the Parameter class. Is there a best way to use Parameter/GenericParameter? If it is the same shape as the Generic class, and you are just renaming it, that is a good argument for using an ontology term. However, there is less of a learning curve for users if you subclass GenericParameter with your own name. Subclassing can lock you in, and may make life more difficult further down the line if your requirements change. Remember though, hardly anyone will write XML by hand, and we shouldn't worry too much about tool implementation. Still want to make it easier for tool developers, though!

• How should we model time?

• For experiment-specific semantics, when should we extend the FuGE model rather than add information through the use of ontologies?

• How descriptive should extending communities get with their samples? Should it be at the entity or attribute level? Is there a best-practice that should be documented?

• How do we find out if two classes from two different communities are actually the same? Recurring model requirements, e.g. a library of model fragments e.g time and sample.

• Could organism be fitted into FuGE::Bio somewhere?

• There is no date of the Action in the ActionApplication. You could have a time parameter that comes in when you add it to your own subclass of Action/ActionApplication, and then provide a different value for that parameter in ActionApplication.

• Somewhere, the distinction between Action and Protocol should be defined.

• In general, we should describe a modelling best-practice to tell what is considered “standard” procedure.

• Data package: internal versus external data

• There may be an issue with describing physical materials within Protocols versus ProtocolApplications (theoretical materials vs physical materials, SubstanceMixtureProtocol was designed to account for this problem)

Last week I attended the first RSBI (Reporting Structure for Biological Investigations) Workshop, carrying with me a multitude of hats. RSBI is a working group committed to the progression of standardization in multi-omics investigations. The purpose of the workshop was to examine and offer suggestions on the initial draft of ISA-TAB (more on that in a moment).

My first hat was a FuGE-user's hat, as the triumvirate of standards upon which RSBI is built is the Functional Genomics Experiment Model (FuGE), the Minimum Information for Biological and Biomedical Investigations (MIBBI) Project, and the Ontology for Biomedical Investigations (OBI). I was asked to give a current status update on FuGE itself, and on any communities that have already built extensions to FuGE. Andy Jones from Liverpool provided me with all of the hot-off-the-press information (my FuGE slides) - thanks Andy!

My second hat was a SyMBA-developer's hat. SyMBA uses FuGE to build a database and web front-end for storing data and experimental metadata. We use it in-house to store all of our large, high-throughput 'omics data. The use of FuGE in the system made it relevant for the workshop (my SyMBA slides, more SyMBA slides).

My final hat was a CISBAN-employee's hat. I work in the Wipat group there, and CISBAN is one of the "leading groups" involved in RSBI. As such, I was CISBAN's representative to the workshop.

The reason for the workshop, as stated earlier, was the evaluation of ISA-TAB, a proposed tabular format whose purpose is to provide a standard format for data and metadata submission into the formative BioMAP database at the EBI. ISA-TAB would have two uses:

1. Humans: As a tabular format, it is quite easy for people to view and manipulate such templates within spreadsheet software such as Excel.
2. Computers: As an interim solution only, ISA-TAB would be used as a computational exchange format until such time as each of the FuGE-based community extensions are complete for Metabolomics, Proteomics, and Transcriptomics. At this time, ISA-TAB would remain available for human use, but there would be a conversion step into "FuGE-ML".

The scope for ISA-TAB is large, and this was reflected in the attendees of the meeting. Representatives from ArrayExpress, Pride, and BioMAP were of course present, but also attending were people from the Metabolomics community, the MIACA project, toxico- and environmental genomics, and the FDA's NCTR.

A full write-up of the results of the workshop will soon be available online at the project's RSBI Google Group, so I'll leave it there. It was an exciting meeting, with fantastic food and even better discussions on getting public databases organized quickly for simple, straightforward multi-omics investigation data and metadata submission.

You can contact the RSBI via rsbi@googlegroups.com.

The Centre for Integrated Systems Biology of Ageing and Nutrition has developed a Data Portal and Integrator (CISBAN DPI) based on Milestone 3 of the Functional Genomics Experiment (FuGE) Object Model (FuGE-OM), and which archives, stores, and retrieves raw high-throughput data. We are pleased to announce that the CISBAN Data Portal and Integrator is now available in a public sandbox version. Please note that this release is still at an early beta stage, and any data you may upload to the server may be deleted at any time. You will need a logon to access this database, which you may request from the helpdesk. This is a low-level of security that will only serve to prevent anonymous load on the database and to keep your sandbox area separate from others. For more information on the sandbox DPI, please visit the DPI's technical documentation.

Until now, few published systems have successfully integrated multiple omics data types and information about experiments in a single database. The CISBAN DPI is the first published implementation of FuGE that includes a database back-end, expert and standard interfaces, and utilizes a Life Science Identifier (LSID) Resolution and Assigning service to identify objects and provide programmatic access to the database. Having a central data repository prevents deletion, loss, or accidental modification of primary data, while giving convenient access to the data for publication and analysis. It also provides a central location for storage of metadata for the high-throughput data sets, and will facilitate subsequent data integration strategies.

We encourage you to upload data and create as many experiments as you like so that you may determine if this application may be of use to your own research group. We also appreciate you contacting us with any comments or questions you may have.

Useful links:

• project page
  
• technical documentation
• sandbox DPI