Paradoxically, the tremendous downpour of microarray results prevents a simple use of expression data. Therefore, we propose a thematic entry to public transcriptomes: you may for instance query a gene on a “Stem Cells page”, where you will see the expression of your favorite gene across selected microarray experiments related to stem cell biology. This selection of samples can be customized at will among the 6462 samples currently present in the database.

Every transcriptome study results in the identification of lists of genes relevant to a given biological condition. In order to include this valuable information in any new query in the Amazonia! database, we indicate for each gene in which lists it is included. This is a straightforward and efficient way to synthesize hundreds of microarray publications.

A special feature of Amazonia! is the field of human stem cells, notably embryonic stem cells.

ENSRNOG00000018677 1368832_at 25233
ENSRNOG00000002079 1369102_at 25272
ENSRNOG00000043451 25353
ENSRNOG00000001527 1388013_at 25408
ENSRNOG00000007390 1389538_at 25493

In the example above I need '25353', which does not have corresponding affy_probeset_id in the 2nd column.

It is clear how to do that:

This outputs a column of required IDs (EntrezGene in this example):

116720
679845
309295
364867
298220
298221
25353

However, I need these IDs as a comma-separated list, not as newline-separated list.

There are several ways to achieve the desired result (only the last pipe commands differ):

These solutions differ in efficiency and (slightly) in output. sed will read all the input into its buffer to replace newlines with other separators, so it might not be best for large files. tr might be the most efficient, but I haven't tested that. paste will re-use delimiters, so you cannot really get comma-space ", " separation with it.

Sources: linuxquestions 1 (explains used sed commands), linuxquestions 2, nixcraft.

I have found many tools which claim to facilitate this procedure. Some of them are reviewed below (in no specific order).

Pathway Explorer by Bernhard Mlecnik was last updated in 2007, but is fully functional (I believe it is being maintained without changes to the last-updated date). Both online and downloadable Java applications are available. Note that for downloadable application you will need to obtain a license key - the procedure is well documented and was very fast for me.

Pathway Explorer supports import from 3 sources: KEGG xml files, biocarta URLs, and GenMAPP URLs. Import from KEGG does work as described in the short manual, and seems functional (I had some problems exporting/saving the resulting picture, but didn't investigate further). Biocarta import seems to work, but for some reason does not display expression levels of pathway components. I could not test the import of GenMAPP pathways, because they are not available online.

I found Pathway Explorer good, but then switched to PathVisio (reviewed next), because for some reason Зathway Explorer was recognising only a small fraction of genes from my expression data. It could be that identifiers mappings are outdated, but this is just a guess.

PathVisio appears to be a spin-off of GenMAPP and WikiPathways. It excells at importing/visualizing WikiPathways data, which even comes bundled with PathVisio Java application. It is easier to use than Pathway Explorer, and it seems to recognize more genes (although still not all the genes which are present in the data). There is KEGG pathways support, but it is not always usable - many edges (links between genes/proteins) are absent, so instead of a pathway you get a bunch of nodes relevant to a pathway, but cannot really see how they are connected. PathVisio supports an insanely long list of database identifiers, so it is highly unlikely that you will have to map your data to use a different identifier. This pathway mapper exports to several formats, including PNG and PDF.

I could not fully test AffyWEB, because it doesn't list rat arrays we used. Trying their barley genome example did work, so the tool is probably functional. It overlays your expression data onto KEGG pathways.

G-language Microarray System is a comparatively simple pathway visualizer. It accepts CSV files containing EntrezGene IDs column with a single column of expression values normalized to 1-100 range, fetches requested KEGG pathway, and generates a Flash (SWF) object depicting that pathway with coloured components. It does work with sample data. I was too lazy to normalize my expression data to [1;100] range, and SWF is not exactly a usable format, so I haven't tested this tool any further (you can right-click to zoom in the flash pathway below).

If time permits (or work requires) this post may be extended with the reviews of GenMAPP, GEPAT, KEGG2heatmap script, EGAN, MapMan, Pathway Miner, ArrayXPath, VisANT, SpotXplore, and maybe others.

Please comment to share your experience using pathway expression overlaying tools or to suggest other tools.

It might be easier to achieve the same results with a Perl script calling NCBI's e-utils.

Here's a simple R script to do just that. It is abundantly commented, and also contains an optional (commented out) fragment which allows the removal of more low-variance, low-intensity probesets.

Hint: click the "plain text" box header to be able to right-click the code, "Select All", and then "Copy".

Sample use:

> source("script.R")
> expr.filtered = filter_below_spikes(eset)

Comments and suggestions are welcome.

Although it has "bioinformatics" on the title page, this is a good and very easy to understand make intro.

Original post is here.

http://bacteria.ensembl.org
http://protists.ensembl.org
http://metazoa.ensembl.org

During summer, two more sites - for Fungi and Plants - should be made available.

Learn more about Ensembl Genomes project.

There are also some easter-egg-like features: try hovering the BioGPS logo in the top left corner several times...

To cut the long story short, here's the list of changes in the new Ensembl 51 webcode release. Other changes to Ensembl in release 51 are also available.

One of the new features which caught my attention is the ability to add custom tracks in Ensembl (which is a long-available feature in UCSC Genome Browser). Interestingly, you do not even have to be logged in to use this feature. We shall be considering providing the TFBS custom track for several species, as predicted de-novo by our evolutionary conserved tfbs search tool (binding site finder), but this is a long shot, given the already published COTRASIF development roadmap.

There is one more great news which is kinda insufficiently highlighted: the brand-new Ensembl Genome Browser website, which (as planned, it hasn't yet started operations) will provide access not only to vertebrates, but also to other taxonomy groups. The full list is:

• Metazoa
• Protists
• Bacteria
• Plants
• Fungi

CLANS runs (PSI)BLAST on your sequences, all vs all, and clusters them in 2D or 3D according to their similarity. This method allows for rapid classification of huge datasets and has the advantage over, lets say, phylogenetic tree, that one can quickly assess results of the clustering in a visual way (I cannot imagine making any sense of looking at phylogenetic tree with 1500 branches, while the graphical output, as on the animation below, is pretty easy to read).

However, with the E!50 release, the Compara database was dropped.

Looking for another option to get orthologs from Ensembl (using martservice, via biomart.org), I tried using the standard query - selecting "Homologs" group on the "Attributes" page for a single species database, and then selecting appropriate second species to get orthology mappings.

Imagine my surprise, when not only in the interface, but also in the generated XML file I found attribute names like "cow_ensembl_gene" :-O

I only need 11 species at the moment, and excluding the sufficiently unique name mappings like "zebrafish - danio rerio", there is a number of questionable mappings: "yeast" for S. cerevisiae (could be S.pombe), "rat" for R. norvegicus (could be R.rattus), "anopheles" for A.gambiae (could be some other Anopheles). Other mappings might be also non-unique, especially for people working with different species of the same genus.

Am I missing some system in this naming "convention", or am I the only one who finds it strange?

Is there a way not to use "common species names" when importing orthology data from Ensembl with the help of martservice?

Update: it appears that conference domain name http://www.icsb-2008.org/ was not maintained after the conference, so I had to remove all the links to that website (which now appears to be owned by someone not related to ICSB). However, there seems to be a mirror of ICSB-2008 at http://www.gmm.gu.se/groups/icsb08test/.

Synopsis: in this post I present a personal-perspective report on the 9th ICSB (with a condensed ICSB-2008 photo-report in my gallery).

I took part in almost all the conference events, starting with pre-conference tutorials and finishing with post-conference workshops, and including the Viking Dinner.

On August 22 (the tutorials day), I attended the tutorials by SBW team, Chris Myers (iBioSim), and CellDesigner 4. Out of these, I liked iBioSim tutorial the most: it had a balanced combination of presented theory and hands-on experience using the program. iBioSim is positioned as (and actually appears to be) a gene-network computer-aided construction software (or, gene regulatory network CAD - GRN CAD). I recommend reading through the Myers group homepage, installing the iBioSim tool (I had problems running it on Linux, but on Windows and Mac it works fine - as long as your saved project's path has no non-latin symbols and spaces), and reading through the tutorial which is included in the iBioSim tool (in the help menu, choose Help, then scroll down the opened page, and click Tutorial).

CellDesigner's tutorial was also good, and referring to my older post on choosing cell modelling software, it is clear that CellDesigner is getting better with the new versions; it does include SBW inter-connectivity feature, and also can use COPASI for modelling. The SBW tutorial was probably somewhat outside the field of my experience, though I did gain some tool use experience and did learn the purposes for which the SBW package can be used. It should be noted that SBW isn't only a "workbench" now, as it includes reaction modelling and simulation tools itself, so it can be used without the conjunction with external tools (as it was initially intended).

On the 23rd of August, there were two more tutorials - Introduction into parameter estimation with COPASI (see also here), and Reaction Network theory for systems biology. To me personally, these were not as exciting as iBioSim , but nevertheless useful.

Here's ICSB tutorials program.

During the main conference event (on August 23-27), we had a number of parallel sessions on various SB-related topics. As from my point of view, there were two strongly exposed main topics: quantitative systems biology (actually, I was really impressed by the number of high-quality QSB studies presented), and... funding! The FUNDING topic took about 25-30% of the time of discussions; it was also tightly intertwined with the needs of the pharmaceutical industry (there was a dedicated session on this, too, and it was also somewhat about funding). It should be noted, that AstraZeneca and Novo Nordisk were the Platinum sponsors of the ICSB conference. Also, funding opportunities seem to be relatively good in Europe, especially for the integrative German projects - such as a probably well-known HepatoSys project (the results of which, unfortunately, are not publicly available - at least yet). However, in addition to the already known HepatoSys, I learned about a number of other large Systems Biology projects being carried out - such as ENFIN, APO-SYS, SYBILLA, UNICELLSYS and many others (see the full ICSB conference program for details).

For me personally, the main (and the most easy to comprehend) bits of information were obtained from the posters devoted to the reconstruction of GRNs. I've found around 15 [potentially] interesting posters - all of which were scrupulously photocopied for further referencing (our systems biology group has just started working on the GRN reconstruction problem).

Also, there was some interest in the tool I presented - the COTRASIF. Although it is not strictly systems-biology (actually, it is pure genomics tool), there were several people interested, and also providing valuable suggestions and feedback. To summarize:

1. we'd better put in TFBS enrichment statistics - showing how strongly is each promoter "enriched" with the sought TFBS (the higher the enrichment - the higher chances that that gene does respond to the TF; this parameter is a higher-level statistic than a plain old score)
2. we need to release the standalone (non-web) binary of the HMM finder tool. This was suggested by the ChIP-seq practitioner - such a tool would allow to better define the boundaries of the experimentally identified binding sites. Clearly, if it were to be used as ChIP-seq-tool, it would better have some good I_c filter to cut off non-informative sequence flanks, and also an internal filter of the resulting Markov matrix I_c
3. we do need to increase the pre-defined promoter size. Actually, we'll increase the upstream-from-TSS part to 2kb (from the current 800b). And closer to the end of October we'll introduce the whole-genome search option
4. we need to publish an article comparing PWM method to HMM method, and providing the FP/FN statistics for both methods as implemented by our tool, plus the FP/FN statistics after applying orthology filtering. Actually, we are working on that, and an article should be re-submitted at the beginning of October

We also had social program - an excursion through the Archipelago to the Island of Marstrand, followed by the Viking dinner at the Carlsten Fortress - one of the best-preserved stone fortresses of the Northern Europe. The 2.5h boat travel was pleasant - especially thanks to the unusually warm and sunny weather, which lasted for the whole conference (it only got somewhat colder on the final workshops day). I liked the dinner, although 3 meat dishes is too much even for such a seasoned meat-eater as I am You can see some excursion photos in my gallery.

The next ICSB-2009 will be held at Stanford in California, USA; ICSB-2010 is scheduled to be held in Edinburgh, Scotland, UK. The place for ICSB-2011 is already being negotiated (it's getting similar to the Olympic Games country scheduling procedures).

Here is formal definition:

high-throughputomics

the term is used to denote/mention any or all of the modern high-throughput techniques (in all of, but not limited to: genomics, transcriptomics, proteomics, ...), together with derived/applicable data-processing approaches. All the "networks" things also conveniently fall into the high-throughputomics definition

As this is a general term, it might be even suitable as a conference title (but NOT for ICSB, which I'm waiting for eagerly).

For a shorter and informal (spoken-only) term, putomics can be used:

putomics

spoken-only, informal short form of high-throughputomics

Putomics is also conveniently similar to "computation" (computomics):

computomics

application of computer hardware and software for the analysis of massive amounts of data, obtained using high-throughput methods; this is a research sub-field of high-throughputomics

P.S.
For easier citing:

Tokovenko, Bogdan. New bioinformatics term: high-throughputomics. 2008-07-16. URL:http://bogdan.org.ua/2008/07/16/new-bioinformatics-term-high-throughputomics.html. Accessed: 2008-07-16. (Archived by WebCite® at http://www.webcitation.org/5ZMD9DITU)

The International Conference on Bioinformatics of Genome Regulation and Structure is the bi-annual event. It features several bioinformatics sections, which IMO cover most of bioinformatics sub-fields.

The Sixth conference, BGRS-2008, was well-organized and had something to offer to everyone. By far the largest section was Genomics and Transcriptomics (at least if judging by the abstracts book and by the posters presented; talks given were distributed more equally between sections). As I did some work in genomics (namely, our COTRASIF tool), I had quite a load of info to digest, and many new potentially fruitful contacts to establish (which I did quite good).

The second section on my scale of priorities was "COMPUTER ANALYSIS AND IMAGE RECOGNITION IN SYSTEMS BIOLOGY", which had several interesting researches presented in the field of spatial/developmental modelling. There was a very good talk on model reduction (with an actual example) for the purposes of both comparing different models and decreasing the model complexity without sacrificing model-predicted outcomes.

As for the other sections, I didn't find them interesting enough. Fortunately, there were social program events scheduled for every day, so I visited the Novosibirsk zoo and the Archaeological museum. I did not do as many pictures as I usually do at conferences/schools, because there were two photographers at the conference, and their photos can be freely seen here and here.

Most of the conference participants could speak Russian (I'd estimate the group of Russian-speaking participants at 90% of the number of participants), even though they were coming from e.g. Singapore or USA. But the official conference language was English, and the 10% of non-speakers were far not underprivileged, which goes well with the international status of the conference.

After the conference, there was a BGRS-2008 summer school. As I stayed for some extra days, I managed to attend up to 90% of the school's events (including the guided tour to Novosibirsk ). For me, summer school was somewhat less useful than the conference, but nevertheless such presentations as on Petri nets and about SABIO-RK/Sycamore were informative and will be used in my future work.

There were 3 prizes for the student presentations; winners are at the end of the page.

Certificates were given after successful school completion. As I wasn't registered, I can now only print out the empty certificate, which is to signify that I did not attend the last day of the school and thus was disqualified .

Just found that there are also some photos from the organizers.

There was also a football (soccer) game between the ICG team and the school participants team. I'm a fan of neither watching nor playing football, so I skipped this event altogether.

First article on topic: Fast network component analysis (FastNCA) for gene regulatory network reconstruction from microarray data.

Another one, on combining different high-throughput data sources to get higher-quality results: Uncovering signal transduction networks from high-throughput data by integer linear programming.

I'm especially interested in time-series network reconstruction algorithms. If you have a good advice to share with a newcomer to the networks field - don't hesitate

If you are interested - have a look at the News page, where there is information on joining COTRASIF Google group. For non-public enquiries, please use my contact page.

Note: the problem of identifying eukaryotic transcription factor binding sites stays acute for many years in a row - see e.g. the most recent Eukaryotic transcription factor binding sites - modelling and integrative search methods.

Note, that exactly the same method can be used to allow any software, which supports proxies but not proxies with authentication, to be able to access the internet.

First, let's outline what we will do:

1. get a proxy which supports on-the-fly modifying of HTTP headers. I used Proxomitron (which is a great tool, BTW!), and recommend using 4.5 June release. You need to have privileges sufficient for installing your local proxy of choice.
2. you need to know the ip (or hostname) of your proxy, proxy port, and both user and password for that proxy

First, install your proxy of choice. In this example, I installed Proxomitron.

Second, you need to configure your local proxy and browser. With Proxomitron:

1. launch proxomitron
2. an eye in a triangle will appear in your taskbar. click it once to bring up the main window:
3. you need to set the checkboxes as I did on the screenshot above
4. click the 'proxy' button, and enter your proxie's host and port (semicolon-separated):
5. optionally, click 'config' in the main window and set desired options, including the default port for local connections (which is 8080 by default)
6. configure your browser to use Proxomitron. Set proxy host to localhost, port to 8080 (default). More info on configuring browser proxy is available either in browser manual, or here for older browsers.

Third, you need to know the authentication string sent to your organisation's proxy server by your browser. You can see that string in the headers your browser sends out at each request. There are multiple ways to see headers. I recommend either using Live HTTP Headers FireFox add-on, or the Proxomitron's "Log window". You can also just calculate the hash.

The string you are looking for should be similar to:
Proxy-Authorization: Basic Yi5OLNrVa242Zw5rBzPpZxl1ZxBhDf==
(it is the hash of your proxy user and password).

Here is what you need to do to see this string using Proxomitron (assuming Proxomitron is already launched and main window open):

1. launch Proxomitron
2. click the 'Log Window' in Proxomitron main window
3. now try accessing e.g. google.com in the browser configured to use Proxomitron. You should get usual HTTP authentication form, asking for username and password. Enter correct data here. Now look into the 'HTTP Message Log' window - you must be able to locate the string we are looking for:
   

The last thing you need to do is to add a rule to your proxy to send the authentication header with every request.

With Proxomitron, do this:

1. click the 'headers' button:
   
2. select the Proxy-Authorization filter, and click 'edit'
3. in the 'Replacement text' field, paste yours auth-string ("Basic ....")
4. OK, Apply. Do not forget to set the checkbox in the 'Out' column for the Proxy-Authorization rule.

This should be all. Now just open Cytoscape, Edit=>Preferences=>Proxy Server, HTTP, localhost, 8080.

This is it.