OpenTox Euro 2013: call for abstracts

Later this year OpenTox Euro 2013 will take place in Mainz:

I also created a page on Lanyrd where you can enlist yourself, preferably with your Twitter account. BTW, the hashtag to be used is #oteu13:

You can submit abstracts here latest by 30 June 2013. There will be sessions around these optics: Open Infrastructure and Application Development, Integrated Data Analysis, Visualisation, Cheminformatics, Bioinformatics, and Systems Biology.

ToxBank: the next generation toxicology

Update: the paper should now be freely downloadable.

Before I moved to my current position in Maastricht, I had the great pleasure to work with Prof. Roland Grafström (check his pathway bioinformatics done with his then PhD Rebecca) and Prof. Bengt Fadeel at the Karolinska Institutet. During this year I part-time worked on ToxBank and part-time on nano-QSAR, and worked on semantics, predictive toxicology, and Open Data. This blog post is about the ToxBank work.

I promised firework, and the first rockets are heading upwards: a key ToxBank paper has now been published in Molecular Informatics. Pekka Kohonen wrote up a nice overview of the ToxBank project, the current platform (based on RDF, REST, ISATab, and OpenTox (my archives)), and the test compounds that the SEURAT-1 cluster identified. Various bioinformatics approaches were used to visualize the diversity of the selected compounds. The idea is that the all EU FP7 projects in the SEURAT-1 cluster (consisting of six consortia) will test at least these compounds, creating a rich data set of toxicology-related data for these compounds.

As a temporary, quick solution I proposed the Semantic MediaWiki to create a semantic knowledge base, which was extensively and very productively continued by David from Leadscope. This way, we could easily list all compounds, by doing a search, rather than manually adding them:

Each compound has extensive information on the mode of action, physicochemical properties and more (such as here for acetaminophen):

All this information is available as semantic data. For example, check this link. Network and Gene Ontology analyses on these compounds have been performed, and presented in the paper, further confirming the diversity of the compound set. This leads to possible integration of their work with WikPathways and PathVisio, and I will do my best to get the right people talking to each other.

The ToxBank project further develops Open Source software for an online data warehouse for hosting experimental data on these compounds. A mix of approaches is used here to base their warehouse on, including OpenTox (RDF and REST(-like)-based), ISATab, and various ontologies.

In designing their software, they use a pretty unique approach for EU projects, based on formal requirement analyses protocols, resulting in a user-oriented platform. Now, there is much to say about who the user is, and in fact, there are multiple user types, called personas, and ToxBank takes that idea into account.

Therefore, in many ways, ToxBank is, in my humble but somewhat biased opinion, a project that leads the (predictive) toxicology community into a new era. Congratulations to the full ToxBank consortium! It was great being part of it!

Kohonen, P., Benfenati, E., Bower, D., Ceder, R., Crump, M., Cross, K., Grafström, R., Healy, L., Helma, C., Jeliazkova, N., Jeliazkov, V., Maggioni, S., Miller, S., Myatt, G., Rautenberg, M., Stacey, G., Willighagen, E., Wiseman, J., & Hardy, B. (2013). The ToxBank Data Warehouse: Supporting the Replacement of In Vivo Repeated Dose Systemic Toxicity Testing Molecular Informatics DOI: 10.1002/minf.201200114

My #ACSPhilly #skolnik2012 slides for "Semantic pipelines to molecular properties"

Plotting molecular properties for (sub)sets

For a toxicology paper we are writing up, I need to create a few plots showing how the toxic and non-toxic molecules differ (or not) with respect to a few molecular properties, such as logP or the molecular weight. The rcdk package provides all, of course, except for a nice convenience method (or does it?) to make a plot. That is, I just want to do something like:

plot.propdist(
  mols,
  selections=list(all, actives, inactives),
  descriptor=
    "org.openscience.cdk.qsar.descriptors.molecular.WeightDescriptor",
  main="", xlab="Weight"
)

And now I can. The result looks something like:

Not much difference in this plot. The colors can be changed, if you like, overwriting the rainbow defaults.

The source code of my method (licensed MIT):

ToxBank and SEURAT-1

Update: these are my personal experiences, and do not reflect that of other people and/or organizations.

The first half year of the ToxBank EU FP7 project (co-founded by Colipa; I think I am legally required to mention them, and I am happy to do so either case) I am working on (50%) has giving me mixed feelings. ToxBank has a great team of people (and great names in the other cluster project too!), and I am quite happy about the results we made. What results, you may ask. Well, indeed: they exist, and nice results too! It's just that they are not so visible.

That is the part I am less happy about: legalities. It took months for the consortium agreement to get finalized, and then there is a cluster agreement for the whole of SEURAT-1. Information is monopolized, and there is a general scare to accidentally release information which others may claim IP. It slows us down; it inhibits new collaborations and thus serendipity. Naive and idealistic as I am, I say this is bad for science.

But, the community is positive about Open nowadays, one achievement of the gold Open Access journals, I guess, and we hosted a workshop on Open Data recently too, which was well attended. People realize that openly sharing data has a role in science (see also this post).

Anyway, the goals are great of SEURAT-1. There now is an official website, and I am pretty sure I am not disclosing any trade secrets. SEURAT (Safety Evaluation Ultimately Replacing Animal Testing) has as ambitious goal to make animal testing obsolete. The ultimately is there to reflect this will not happen any time soon, but at least we die trying (this is also why there is a -1 in the name... there may be follow projects, as outlined in the Vision and Strategy). Of course, that following up makes Open Source and Open Data important, in my personal opinion. Fortunately, more and more people share that opinion. I hope my direct and/or indirect contributions to ToxBank can set an example.

The title of the -1 project is "Towards the replacement of in vivo repeated dose systematic toxicity testing". So, that will be more or less the focus of the ToxBank data warehouse. The types of data will be very diverse, and includes many areas of the omics space, including my favorite: metabolomics. To allow a systems toxicology approach, a short list of test compounds will be established. As part of ToxBank we have set up a Semantic Web system, allowing these compounds to be part of the Linked Data network. However, here comes the legal stuff again, and the wiki is not generally accessible; only to SEURAT-1 member (more precisely: will be very soon).

And that makes it impossible for me to start call in the community to run that favorite tools against these compounds. For example, to calculate solubilities in various solvents. That is information useful to our compound evaluation, and would contribute to the SEURAT-1 project! But I cannot do that right now :(

But, we're just 6 months into the five year project. I think we'll see a lot of firework later! The hurdles may slow us down, they will not mean we will not reach what we want.

My machine-readable ELN

Now with embedded PDFs.

Importing Nanotoxicity Data with SPARQL into R for analysis

Not so long ago I wrote about [i]mporting RDF input in R for analysis. I am collecting nanotoxicology data in a Semantic MediaWiki with the RDFIO extension installed (by Samuel), allowing me to SPARQL that data directly from R. There is nothing much structural to visualize at this moment, so I'm skipping the Bioclipse intermediate. I did show some visualization of the data itself in the wiki, earlier this week.

Anyway, release 1.2 of rrdf is on its way, adding a sparql.remote method for running SPARQL queries at remote repositories. It also has a patch by Ryan Kohl, to support CONSTRUCT-like SPARQL queries.

I haven't aligned my wiki with any ontology yet, so the properties have SMW-like resource form, which makes the SPARQL a bit weird looking. Other than that, the code to pull in nanotoxicology data from my data notebook now looks like:

library(rrdf)

endpoint = "http://127.0.0.1/mediawiki/index.php/Special:SPARQLEndpoint"

query = paste("PREFIX w: ",
 "SELECT ?min ?max ?zeta WHERE ",
 "{ ?inst a w:Category-3AMetalOxides . ",
 "  OPTIONAL { ?inst w:Property-3AHas_Size_Min ?min . }",
 "  OPTIONAL { ?inst w:Property-3AHas_Size_Max ?max . }",
 "  OPTIONAL { ?inst w:Property-3AHas_Zeta_potential ?zeta . }",
 "}"
);

data = sparql.remote(endpoint, query)

Which results in a data matrix that looks like (mind you, this matrix is numeric, needing a bit of rrdf 1.3 functionality):

> data
      min max  zeta
 [1,]  15  90    NA
 [2,]  15  90    NA
 [3,]  15  90    NA
 [4,]  15  90    NA
 [5,]  15  90    NA
 [6,]  15  90    NA
 [7,]  15  90    NA
 [8,]  15  90    NA
 [9,]  15  90    NA
[10,]  15  90    NA
[11,]  15  90    NA
[12,]  15  90    NA
[13,]  10 100  34.2
[14,]  30  60 -17.3
[15,]  20  30   1.8
[16,]  15  90    NA

So, now it is time for some PCA.

In Silico Toxicology

Today my copy of In Silico Toxicology: Principles and Applications (Issues in Toxicology) arrived at the local Library. Library with a capital L: we requested the book 1.5 weeks ago, got confirmation it got ordered last week Monday, and just picked it up. Well done!

The book covers in 24 chapters the prediction of toxicological properties of small molecules, and extensively discusses aspects of QSAR studies. As such, various Blue Obelisk tools are described, including the CDK (page 184 and 413), Bioclipse (page 414), JOELib (page 185), OpenBabel (page 414), Oscar (page 415), as well as other Open Source tools, including AMBIT (page 315 ff), InChI (page 72), Toxtree (page 313 and 417), and others. (Nina, should I classify AMBIT and ToxTree as Blue Obelisk projects, now that you are a Blue Obelisk Award winner?)

Much of these are actually listed in Chapter 17, Open Source Tools for Read-Across and Category Formation, by Nina et al., but also worth mentioning is the prominent placement of Open Source tools in Chapter 6 by Uko Maran et al., Molecular Descriptors from Two-Dimensional Chemical Structure, where the REACH documentation focuses on proprietary tools.

Obviously, these are not the bits I am eager to read. Instead, I'm very much looking forward to reading the chapters on data quality (Ch. 4), model validation (Ch. 11), application domain (Ch. 12), linking chemical structures to adverse reactions (Ch. 14), and toxicokinetics (Ch. 21). The book sums up to some 669 pages, so it will keep me busy for the next few hours ;)

The 9th International Conference on Chemical Structures (ICCS)

Later this year the ninth International Conference on Chemical Structures (ICSS) conference will be held in the Netherlands. I had the pleasure of joining this meeting, I think, eight years ago, when I was doing my PhD in Nijmegen. Mind you, I did not attend the conference; I helped with the organization ;) That was a good deal, particularly because I got to meet many cheminformaticians while working behind the registration desk ;)

Actually, my gravatar still reflects that meeting, as it is a picture taken on the boat trip on the Markermeer. That was one great boat trip: I steered a driemaster, and helped out on the boat on ropes outside the deck, meters above the water. Cheminformatics can be so nice! The photo was taken during a calmer part of that boat trip :)

Back to the ICCS. It's one of the bigger cheminformatics meetings, and likely the best after the yearly GCC meetings. Mind you, the term cheminformatics reflects more the methods than the domains. Indeed, the meeting's Call for Papers lists many topics highly relevant to my position here at KI, including chemogenomics, (Q)SAR, literature mining, "integration of medical and biological information" (including semantic web technologies), and in-silico analysis of toxicology, drug safety, and adverse events.

Depending on the schedule this year, I may actually submit an abstract based on what we will do in the next year, and see what happens. The CfP deadline is 31 January.

Karolinska Institutet

Hi all, and a happy 2011! After a turbulent December (finishing up in the Oscar project), holidays, etc, I am starting to get some sense of organization in my new position at the Institutet för miljömedicin at the Karolinska Institutet in Stockholm. I will be using cheminformatics and chemometrics methods in toxicology studies, and work in the groups of Prof. Roland Grafström and Prof. Bengt Fadeel.

The actual work will crystallize in the next weeks, but here are two pointers. One is ToxBank, for which the website should go live this month, but Google will provide some ideas about this FP7 project. The other part is into nanotoxicology (see e.g. doi:10.1039/C0NR00535E).

So, if you are around in Solna, give me a ping!

My talk at Imperial College

Yesterday I was guest with Judy at the Department of Surgery & Cancer at Imperial College, where I presented the what I am working on. As I met up in a pub with Ron (my former PhD supervisor, who now works on metabolomics at the Istituto Agrario San Michele all'Adige in Italy) the night before, the presentation does share many slides from previous talks, but also adds a few new ones.

Open Data, Open Source, and Open Standards in Drug Discovery, Metabolomics, Toxicoloy

View more presentations from egonw.

It was great talking to Judy about her PhD research on NMR in metabolomics, and Tim about further work in this research. I was interesting to learn that here too they have problems in metabolite identification quick like those when analyzing *C/MS data, and was really happy to hear he is in contact with Christoph about an Open repository for metabolomics data.

Another 'new' slide was one advertising the yesterday launched Open Research Computation which I'll blog about in more detail later today.

Oxford...

Yesterday I arrived in Oxford, after a 3.5 hour bus transfer from London Stansted. Long, boring ride (though I might have seen a few red kites, but seeing that they were near extinct, I am wondering what other large bird of prey has strong split tail like a swallow). Showed once more that the UK infrastructure has hardly changed since the 19th century. Enjoying an undergraduate room at one of the colleges. Pretty basic, but makes me feel more like a human than a tourist. Yes!, undergraduate students are human too! One of the advantages is you get an excellent internet connection :)

Anyways, going to the Predictive Toxicology workshop, thanx to the bursary award I received from echeminfo (see Oxford, August 2010: eCheminfo Predictive ADME & Toxicology 2010 Workshop).

This afternoon I walked around a bit, watching all the old buildings. But I guess being here without anyone to share it with, and that it just looks Cambridge, makes me not-so-much impressed. Moreover, it's too busy with tourists and people randomly wearing Oxford University sweatshirts. Small and nice was the Museum of the History of Science, with some nice chemical pieces, like this one:

Buildings like the Radcliffe Camera are nice on the outside, but closed. Seems I have to become a fellow first. This is what it looked like today:

Quite interesting too was the Oxford University Press shop. I'm a sucker for books. Apparently, you can just write a book and publish it. For example, an extensive list of dictionaries on about anything... and since I have been writing several book chapters right now, perhaps this is actually an interesting route...

But the question is, of course, how long will we keep reading books... they're the hamburgers of educational material... Kindle and alikes will soon drop in price, and cost some €30 euro. But e-book prices will have to drop too, and I still do not get why an e-book is more expensive than a paperback... (see Amazon, the Kindle edition is more expensive than the paperback??). But then again... they are rich, and I am not.

There was some recent talk about the fact that no one can be Open to the full. You either do Open Data or Open Source, and make a living from the rest. That's where I nicely show I know bullocks of economics. I do BODR, CDK, ... all Open, all for free.

OK. That's a plus for Oxford... it makes you think about things. Perhaps there is something to morphogenetic fields...

My OpenTox Workshop contribution: The Lost Slides

During the nice presentations at the recent OpenTox Workshop, I noted that My OpenTox Workshop contribution: Linking explicit and implicit knowledge was lacking two slides. The slides should have had screenshot of the excellent Bioclipse applications Ola Spjuth has written in the area of computational toxicology. But here they are.

Metabolic Fate
The metabolic fate of molecules can be predicted with the MetaPrint2D feature (see also the main MetaPrint2D page). The feature currently uses one specific method, but the immediate feedback you get while drawing molecules, can basically use any model. The currently used model is developed in a collaboration of Ola with Sam Adams (whom we all know for his JNI-InChI library) at Cambridge University and Lars Carlsson at Astra-Zeneca.

This screenshots shows the visual feedback in the (new) JChemPaint editor in Bioclipse, and on the right we see one interesting Bioclipse feature in action: the cheat sheets. These cheat sheets are inline help documentation which guides the reader through the functionality. But, unlike mere help, cheat sheets can be very interactive and perform some tasks itself, making it easier for the reader to see what was supposed to happen.

L. Carlsson, O. Spjuth, S.E. Adams, R.C. Glen, S. Boyer, Use of Historic Metabolic Biotransformation Data as a Means of Anticipating Metabolic Sites Using MetaPrint2D and Bioclipse, accepted in BMC Bioinformatics.

Structural Alerts, etc
Structural alerts are one method to signal the scientist that the molecule under study needs some more attention (see for example doi:10.1016/j.mrrev.2008.05.003). It helps him decide to continue to look at that particular structure, or to move on. Ola also developed a decision support plugin.

One of the cool features is that, in good Bioclipse habits, deliver a pluggable architecture. This practically means, that anyone can add their own decision rules; those can be added as local software, or as services on a central, institute specific server. The results in this screenshot show that a Bursi AMES data-based model estimates that this molecule is mutagenetic.

O. Spjuth, L. Carlsson, M. Eklund, E.A. Helgee, S. Boyer, Integrated decision support for assessing chemical liabilities, In preparation