News about the STRING and STITCH databases

Combining scores the right way

2010-03-16T13:43:00.001+01:00

With STRING version 8, we began to add prior correction to the scores. That means that we consider how close scores are to the background rate of about 6% for protein–protein interactions, and we remove the random expectation from the scores before we combine them. (At the end, we put the random contribution back in to make it consistent with the case that only a single evidence channel contributes to the score.)

For some applications, you might want to remove certain evidence types from the STRING download files. To compute a new combined score, you can now use the same prior correction we've been using internally. We have started a new BitBucket repository, and added a script to discard channels from the full STRING download files.

STRING 8.2 and STITCH 2.0 released

2009-11-09T14:37:00.005+01:00

We have released new versions of STRING and STITCH!

Here are some of the changes:

protein-protein actions like binding or post-translational modifications are now included
most download files are now under Creative Commons licenses, so academics usually don't need to fill license agreements anymore
bugfix: version 8.1 had accidentally omitted homology transfer in the textmining channel, this is now fixed.
the Flash interactive network viewer has further matured; a simple, lean version is now enabled by default. The full-featured version can be activated by clicking on the "advanced" button below the network
STITCH 2 uses the protein universe of STRING 8
the number of interactions has further increased

API for STRING 8.0 still accessible

2009-09-01T17:20:00.003+02:00

After the release of STRING 8.1, the previous version, 8.0, can still be accessed: http://string80.embl.de. Under this URL, the API continues to work, e.g.:

http://string80.embl.de/api/tsv/interactors?identifier=DRD1_HUMAN

This pattern will continue for upcoming releases (you could also use "string81" as host name now to stay on this version even if we update to a new version).

Quick poll for next STITCH version concerning chemical names

2009-07-23T15:39:00.003+02:00

I'm conducting a small poll over at FriendFeed about abbreviations of chemical names. If you have a opinion about which abbreviation is better in the following cases, please leave your feedback (either on FriendFeed or in the comments here):

10-formyltetrahydrofolate: "10-formyltetra." or "10-formyl-THF"?
acetyl-L-carnitine: "acetyl-L-carni." or "ALCAR"?
dihydrotestosterone: "androstanolone" or "dihydrotestost."?

STRING Cytoscape plugin

2009-07-21T14:00:00.001+02:00

Users of Cytoscape can now natively retrieve interaction networks from STRING !

During a recent workshop at the EBI, a common web service API to query interaction databases (called PSICQUIC) was finalized. Once all interaction databases have implemented this interface, it will be possible to use a single client (a Cytoscape plugin for example) to interact with all of them. We are committed to this initiative, and look forward to the implementations.

In the interim, we have decided to also release a small, custom-made plugin for Cytoscape called StringWSClient, which interacts only with the STRING database.

This allows us to offer users the full range of features that the STRING API allows (e.g. to show all available species, or to resolve ambiguous inputs). Version 1.0 (1.1) supports only the import of interaction networks; upcoming versions will be able to extend existing networks, filter them using STRING specific criteria, etc. The 1.0 version works only with Cytoscape 2.6.1, and 1.1 was released to support the whole 2.6.x branch.

To install it, fire up Cytoscape, open Plugins/Manage Plugins dialog and pick StringWSClient v1.0 from "Network and Attribute I/O" section. You may have to restart Cytoscape to load the plugin. See Cytoscape documentation for details.

Once you have the plugin installed, open File/Import/Network from web services... dialog and
pick the String plugin.

The plugin resembles STRING's web user interface: a field to type queries and the organisms selector. In the background, the query is sent to the STRING database and the resulting interaction network is fetched and displayed.

We're looking forward to your feedback !
Milan Simonovic and the STRING team.

100 API accesses per minute: not a good idea

2009-07-01T09:46:00.004+02:00

STRING was unreachable for some time this morning while it was busy processing ~10,000 API requests in about 1.5 hours. 100 API accesses per minute is not a good idea, as this overloads our server, making STRING (and STITCH) unavailable for everyone. Don't run scripts that access the API in parallel.

If you want to do large-scale analysis on STRING data, you can make your and our life much easier by signing an academic license agreement and downloading the full dataset.

New Release of STRING: Version 8.1

2009-06-24T09:38:00.013+02:00

We are happy to announce that STRING 8.1 has just been released. We have updated the interaction data, fixed a number of bugs and greatly improved the web interface. As always, we keep older versions around to guarantee reproducibility of earlier work (see here).

The interactive network viewer has been re-implemented (it's now based on Adobe Flash version 10), and it gives users the new opportunity to "play around" with the network while keeping the same look and feel as previously.
The proteins in the network can now also be clustered, 'live', via two different methods: k-means and markov chain clustering. The topology can be relaxed after clustering, or in real time by turning on "relaxation" and "cooling". The graph layouting is done by force-directed placement (see here), and the cooling is done by gradually lowering the relaxation variable hat determines the strength of node movements, to zero. Of course, this is merely a first version of the interactive viewer and future versions may well have additional features (in particular in case our users have specific requests).

We have also extended the protein structure previews. These are now not only based on PDB, but we also incorporate homology models from the SWISS-MODEL Repository. And, structure previews are finally shown in the proper context of the protein's domain architecture.

Lastly, we fixed several 'known issues' (i.e., bugs) - such as missing minor chromosomes for some species, and viewer problems with the textmining predictions.

To start playing with the new release, visit STRING 8.1 - and please don't hesitate to send us any feedback, criticism or suggestions...

Have Fun !

The STRING team

Known Issues in STRING version 8.0

2009-02-19T18:01:00.011+01:00

For each STRING version so far, only when we released it to the users did we find the last remaining bugs. Users often email us with their problems, and sometimes we are indeed to blame because there is an error. This is good (we think), because each bug found is a bug fixed - albeit only in the next release, usually.

So far, this is what we have found in release 8.0:

a) Some of our text-mining links do not show up in the corresponding evidence viewer. They are still correct, but the underlying text cannot be recovered and shown, for technical reasons. This happens because we developed a new feature that recognizes generic 'family' names for gene groups (like 'WNTs' for the various, homologous Wnt proteins). Within reasonable limits, such ambiguous names are now expanded to the individual protein members. However, we forgot to update the code of the text-viewer to reflect this ... we will do so in the next version.

b) Unfortunately, some of the prokaryotic genomes in this release are incomplete - in 43 cases we're missing a second (or third) minor chromosome. This was caused by a misunderstanding when parsing files from the RefSeq database: RefSeq provides an overview file that only lists one chromosome for each prokaryote, and we mistook that file for the full listing. Again, this will be fixed in the next release of STRING (on which we are already working). Obviously, we're now writing a new entry in our test suite that will prevent this type of error in the future - we will be checking the final gene counts of all organisms for consistency and also compare these counts against an external reference. Below is a list of affected organisms in the current release; if you're working with any of these, we recommend you continue using version 7.1 of STRING for now.

Luckily, no major model organisms are affected !!

Agrobacterium tumefaciens str. C58
Brucella abortus biovar 1 str. 9-941
Brucella melitensis 16M
Brucella melitensis biovar Abortus 2308
Brucella ovis ATCC 25840
Brucella suis 1330
Burkholderia ambifaria AMMD
Burkholderia cenocepacia AU 1054
Burkholderia cenocepacia HI2424
Burkholderia mallei ATCC 23344
Burkholderia mallei NCTC 10229
Burkholderia mallei NCTC 10247
Burkholderia mallei SAVP1
Burkholderia pseudomallei 1106a
Burkholderia pseudomallei 1710b
Burkholderia pseudomallei 668
Burkholderia pseudomallei K96243
Burkholderia sp. 383
Burkholderia thailandensis E264
Burkholderia vietnamiensis G4
Burkholderia xenovorans LB400
Deinococcus radiodurans R1
Haloarcula marismortui ATCC 43049
Leptospira borgpetersenii serovar Hardjo-bovis JB197
Leptospira borgpetersenii serovar Hardjo-bovis L550
Leptospira interrogans serovar Copenhageni str. Fiocruz L1-130
Leptospira interrogans serovar Lai str. 56601
Ochrobactrum anthropi ATCC 49188
Paracoccus denitrificans PD1222
Photobacterium profundum SS9
Pseudoalteromonas haloplanktis TAC125
Ralstonia eutropha H16
Ralstonia eutropha JMP134
Ralstonia metallidurans CH34
Rhodobacter sphaeroides 2.4.1
Rhodobacter sphaeroides ATCC 17029
Vibrio cholerae O1 biovar eltor str. N16961
Vibrio cholerae O395
Vibrio fischeri ES114
Vibrio harveyi ATCC BAA-1116
Vibrio parahaemolyticus RIMD 2210633
Vibrio vulnificus CMCP6
Vibrio vulnificus YJ016

That's it for known issues so far. But, do keep those emails coming - the feedback is very valuable !!

Homology correction of co-occurrence and text-mining scores (updated)

2009-01-29T11:30:00.001+01:00

[Update 29/01/2009: The homology correction is also applied to the text-mining channel starting with STRING 8.]

In order to avoid that gene duplications lead spurious functional associations, homologous proteins are down-weighed in the co-occurrence and text-mining channels. You will notice this on the score summary page of a link and if you have our SQL dumps.

Here's an example: The co-occurrence view looks fine for this pair of proteins.
However, the total score of 0.204 is less than the co-occurrence score:

The reason for this is that the proteins have some sequence similarity and are therefore down-weighted according to this formula:

effective co-occurrence score = co-occurrence score * (1 - homology score)

(The homology score is calculated from the bit score of the alignment.) In this case:

0.204 = 0.478 * ( 1 - 0.572 )

Linking to individual networks (updated)

2009-01-15T17:30:00.000+01:00

If you want to link to STRING or STITCH from your website, you can use the following URLs for simple queries:

For STITCH, you can use names of chemicals:

http://stitch.embl.de/interactions/aspirin?species=9606

You can also use identifiers, e.g. SwissProt or ATC codes:

http://string.embl.de/interactions/DRD1_HUMAN
http://stitch.embl.de/interactions/A01AD05?species=9606

(The 9606 specifies that you want human interactions, see NCBI taxonomy.)

Update: You can also link to networks with multiple items. As STRING saves the user's preference for proteins/COG mode, it's better to specify the target mode.

http://string.embl.de/interactionsList/zgc:73075%0Dzgc:136854?targetmode=proteins
http://string.embl.de/interactionsList/zgc:73075%0Dzgc:136854?targetmode=cogs
http://string.embl.de/interactionsList/KOG0044%0DKOG3656?targetmode=cogs

http://stitch.embl.de/interactionsList/DRD1_HUMAN%0Dpergolide?species=9606

You construct the URL by concatenating the protein names with "%0D" or "%0A" (an encoded carriage return / newline character).

New Year - New Major Release

2009-01-14T09:44:00.009+01:00

Looks like 2009 will bring a lot of changes for both STRING and STITCH - and to lead the way, STRING has now been upgraded to version 8.0 !

This has been a major upgrade, and it has been some time in the making. We have almost doubled the number of organisms (again), and re-imported all the various pathways, protein-complexes and text-collections. We've also worked a lot behind the scenes, solidifying the API, further automating our data import and updating the way we display orthologous groups, to name just a few examples. All this has been possible only, really, because of our new sponsor - the Swiss Institute of Bioinformatics (SIB). Thanks guys !

More info about this new release is also available from here.

High-resolution images

2008-07-21T20:03:00.003+02:00

We recently implemented a way to export high-res images (300 dpi, click the image below to see an example). This feature will go public with STRING 8 / STITCH 2, but if you're now using STRING or STITCH and want to prepare an image for publication, please get in touch with us (mkuhn embl de) and we can send you the image.

2008-06-26T17:23:00.007+02:00

How we compute scores (Part 1: experiment channel)

This is in response to a a question that we get quite frequently.
Sorry, it's a bit long - but this way it should contain sufficient detail to roughly understand how our scores come about (for the 'experiments channel' at least, and limited to protein mode). Have fun reading !

Christian von Mering (and Lars Jensen).

Procedure to compute experimental scores

first, we import information about which proteins have been shown to interact experimentally, from the following databases: INTACT, MINT, GRID, BIND, and DIP. To a small extent, this also includes experimental data that is not necessarily indicative of a direct physical interaction, such as genetic interaction data. Most, however, are from more-or-less direct, physical detection methods.

then, we map the proteins mentioned in these database onto the proteins in the STRING database - using identifiers, or (if needed) sequences.

next, we group all interactions by their supporting publication (PMID), and make them non-redundant (they might be reported under the same PMID from several databases). We also expand pulldowns of entire protein complexes using the 'spoke' model (i.e. assuming binary interactions from the tagged/immunoprecipitated protein to all of its co-purified partners).

then, we subdivide all interactions into 'small-scale, medium-scale, and high-throughput', based on the number of interactions reported by a single publication. These three classes are delineated by the extent of overlap with benchmark information, see below.

next, for each of these classes, we determine their 'reliability', by comparing them to our KEGG-benchmark. Briefly, an interaction between two proteins is counted as 'correct', when they are both annotated together in at least one 'KEGG-map', i.e. in at least one functional process / pathway. It is counted as 'incorrect', when the two proteins are annotated in KEGG, but never in the same pathway. Note that proteins that are not annotated at all in KEGG are not considered here).

for the small-scale experiments, which are only very few (per paper), we cannot benchmark each paper separately. Therefor, all such papers are lumped, benchmarked together, and we usually find them to be of quite high quality. As a result, we fix their score to some high number, for example 0.900 in the case of STRING version 7.1

for the medium-scale experiments, a separate score is computed for each publication, in a similar manner (some publications are found to report data of better reliability, other of lower reliability).

for the high-throughput experiments (there are less than 20 of these currently), we have enough information to be even a bit more specific: for each interaction in these sets, we can compute a 'raw score' from the data, because there are so many measurements done. Usually, this would be a score that describes how often a measurement has been confirmed, or how specific a particular interaction is, given the occurence of the two protein elsewhere throughout the dataset. These 'raw scores' are then binned, and each bin benchmarked separately, to arrive at a 'calibration curve', again using the KEGG pathways as a benchmark as described above. Thus, for these large sets, some interactions get a higher score, and others a lower score, depending on the information in the entire dataset.

this brings us to the cutoffs that determine whether something is small-scale, medium or high-throughput. This is defined on how many 'true-positives' are in the dataset: To be a large-scale dataset, we require at least 50 true positive interactions to enable the benchmarking. Otherwise, more than 20 true positive interactions will make it a medium-scale dataset, and the rest is small-scale. ("true positives" are defined as interactions where both proteins are in KEGG, and are sharing at least one KEGG map).

then, we have to deal with interactions supported by more than one independent dataset (i.e. by more than one publication). For those, the scores are 'added up'. Of course, they are not literally added up, but rather in a probabilistic integration, like so:

new_score = 1 - (1 - score_a) * (1 - score_b).

and finally, whe have to deal with interactions that are reported in multiple organisms, or in an organism other than the one of interest. This is called 'interaction transfer', and is a very important step to increase coverage. It is described in the 2005 STRING paper. Essentially, the better the orthology situation can be delineated (i.e. clear orthologs for both interacting partners can be identified), the bigger the score fraction that is transferred. Transferred interactions are integrated probabilistically as mentioned above, and interactions that are reported in two very similary organisms (say, mouse and rat), are considered redundant and transferred only once. Note that transferred scores are stored separately from the 'direct' scores in the database, so that all the transferred information can be discarded, if desired.

Downtime Wednesday morning

2008-06-17T11:41:00.004+02:00

The STRING server will get a new disk tomorrow morning (European time), so there will be a downtime for STRING/STITCH. We hope everything will be working again in the early afternoon.

Update: We're back online, with enough room for the next version of STRING.

API also available on STRING

2008-05-19T11:19:00.002+02:00

When I created the API, I only put it on STITCH. Of course there's no reason to not have it also on STRING, so here you go:

http://string.embl.de/api/tsv/interactors?identifier=DRD1_HUMAN

It's in the same state as the STITCH API: Still subject to change, and potentially unstable.

Getting identifiers for a list of genes

2008-04-28T11:54:00.003+02:00

If you want to to quickly get identifiers for a long list of items you can use the following command, which uses wget to repeatedly query the API.

cat protein_names.txt | xargs -i wget -nv -O - \
'http://stitch.embl.de/api/tsv-no-header/resolve?identifier={}&species=4932&echo_query=1' \
> protein_identifiers.tsv

I've also introduced another parameter, echo_query, so that you can see your query item in the output.

No Downtime on Saturday, April 26

2008-04-23T14:22:00.003+02:00

~~There'll be an EMBL-wide power cut on Saturday, April 26. Therefore, our servers won't be reachable at this time. We hope that the computer infrastructure will be re-activated by Monday.~~

Sorry, the plans were changed and not all of EMBL is affected, so we should stay online.

Embedding protein/chemical information into other web pages

2008-03-04T16:49:00.006+01:00

One of the nice things about STRING/STITCH is that you can click on any item and be presented with a helpful pop-up describing the item in question. :-)

As you can see, for a protein, we show links to different servers, the domain structure and if possible a representative PDB structure. For a chemical we currently only show the structure and link to PubChem.

In order to use the same pop-up in Reflect (a cool tool that recognizes and annotates proteins and chemical any web page), we made a service out of it. The functionality is going to change in the future, but here are two working examples:

http://stitch.embl.de/services/iteminfo?node=9606.ENSP00000186982
http://stitch.embl.de/services/iteminfo?node=CID2244
The idea is that you can take this raw HTML and put it into an iframe with JavaScript. (This is left as an exercise to the reader... future versions of STRING may use this technique to make the pages a bit smaller.) For now, it only accepts internal STRING identifiers, which you either get from our download files or from the API.

Servers may be unreachable today (March 3)

2008-03-03T16:40:00.003+01:00

You might have trouble today accessing our servers today because of construction in the server rooms. We apologize and hope that everything will be done soon!

Update: We're back online.

Scope of the API and current plans

2008-03-03T15:05:00.003+01:00

When I announced the API, I didn't devote much space to the intended scope of the API. To make things clearer:

REST/SOAP: We'll only provide a REST API plus a Soaplab2 wrapper for Taverna. Perhaps later dedicated programmers can add a SOAP interface if the demand is sufficiently high.
Queries for bulk data: For implementation and licensing reasons, we'll only provide methods to query by individual items, just like on the web site. If you need access to bulk data, you can download it.
Miscellaneous records: We want to add more query options later for retrieving information from the freely available files. For example: What are the synonyms of this item? To which orthologous group does this protein belong?

Example Taverna workflow

2008-02-22T14:26:00.003+01:00

Taverna is a tool that lets you connect web services from different sources with each other. I've implemented a simple example workflow (.xml): You enter a human protein or chemical of interest, STITCH will identify the matching item(s), generate an interaction network and retrieve the 10 most relevant abstracts. The list of Pubmed ids is then passed on to Whatizit, which highlights disease terms in the abstracts. A simple Python script then counts the diseases.

Try it out; try other things; tell me what you think.
Note: The Python script is called via the Soaplab interface. I tried to do this in Taverna but gave up, it didn't like my XPath (due to the XML produced by Whatizit) and writing a Beanshell script seemed more cumbersome.

We have an API!

2008-02-19T17:00:00.016+01:00

I went to the BioHackathon 2008 in Tokyo and worked on an API for STRING and STITCH. If you think about using STRING or STITCH with an API, and miss features, please get in touch with us either via the comments or e-mail (e.g. mkuhn//embl.de).

Here's what we have to offer so far:

REST interface

The URL patterns are: http://stitch.embl.de/api/[format]/[request]?[parameters]
http://string.embl.de/api/[format]/[request]?[parameters]

Possible formats:

tsv: tab-separated values, with a header line
tsv-no-header: as above, but no header
json: JSON format either as a list of hashes/dictionaries, or as a plain list (if there is only one value to be returned per record)
psi-mi: the interaction network is available in PSI-MI 2.5 XML format
psi-mi-tab: there is also a tab-delimited form, modeled after the IntAct specification. This is easier to parse, but contains less information than the XML format.
url: return the URL of the network image

Possible requests:

abstracts: return a list of abstracts that contain the query item
abstractsList: return a list of abstracts that contain any of the query items
interactions: return an interaction network in PSI-MI 2.5 format (PSI-MI is currently the only format for interactions. Perhaps the PSI-MI tab-delimited form would also make sense? I don't know how a JSON form should look like.)
interactionsList: same as above, but for list of identifiers
interactors: return a list of interaction partners for the query item
interactorsList: return a list of interaction partners for any of the query item
resolve: return the list of items that match (in name or identifier) the query item
network / networkList: in conjunction with the "url" format, return the URL to the network

~~For a full list of possible parameters, please refer to our STRING Soaplab 2 interface. With the help of Soaplab2 / Gowlab, we'll describe the set of possible parameters there.~~ (Doesn't work right now. :-/ )

Examples

To find out which proteins match the description "dopamine receptor" in human, you can use this query:

http://stitch.embl.de/api/tsv/resolve?identifier=dopamine%20receptor&species=9606
http://string.embl.de/api/tsv/resolve?identifier=dopamine%20receptor&species=9606

This gives you a lot of additional info. If you just want to get the list of STRING identifiers, you can alter the query a bit:

http://stitch.embl.de/api/tsv-no-header/resolve?identifier=dopamine%20receptor&species=9606&format=only-ids
http://string.embl.de/api/tsv-no-header/resolve?identifier=dopamine%20receptor&species=9606&format=only-ids

Now, you'll only receive a bare list of ids that you could pipe into other STRING API functions.

To illustrate the difference between normal and "list" queries:

http://stitch.embl.de/api/tsv/interactors?identifier=DRD1_HUMAN
http://stitch.embl.de/api/tsv/interactorsList?identifiers=DRD1_HUMAN%0DDRD2_HUMAN

http://string.embl.de/api/tsv/interactors?identifier=DRD1_HUMAN
http://string.embl.de/api/tsv/interactorsList?identifiers=DRD1_HUMAN%0DDRD2_HUMAN

In the second case, the identifiers parameter contains a list of items separated by new line characters (%0A or %0D).

SOAP / Taverna

In a separate post, I've described an example Taverna workflow. As for SOAP integration, I hope that the Soaplab interface works...

Obligatory beta notice

As all good things these days, this is still in beta (internally, everything in fact runs on our beta server, I'm just making it accessible via the normal STITCH domain to expose it to the web). Therefore, the API might change, be down, ... until STITCH 2 / STRING 8 comes out.

Updates

03.03.2008: Added clarification – PSI-MI is currently the only interactions format.
04.03.2008: Fixed typo – it's "interactorsList"
12.03.2008: Add psi-mi-tab format
19.05.2008: Add STRING API (with same specification)
08.07.2008: Add API for generating network images
16.03.2009: Enabled interactionsList

Mea culpa: missing links from PDB

2008-02-06T14:11:00.000+01:00

I intended to extract protein–chemical links from the PDB (and we wrote this in the paper), but somehow I didn't quite finish the import scripts before we finalized STITCH 1.0. I am sorry about this, and apologize if you are missing interactions.

We are currently preparing the next versions of STRING and STITCH (versions 8 and 2, respectively) and I will import the remediated PDB for the new version. I guess STITCH 2 should come out in Spring 2008.

(Special thanks to Florian Raible for testing his pet molecule and discovering what was missing.)