Analysis: Christmas no longer in vogue!

I have just made an alarming discovery: judging from the biomedical literature, researchers appear to increasingly ignore Christmas.

My plan was to make a funny Christmas post looking at trivialities such as when during the year Christmas-related papers are posted. To this end, I did a trivial text-mining analysis that pulled out all papers mentioning “Christmas”, “Xmas”, or “X-mas” in the title or abstract. As a first check of the data, I looked at how many papes were published each year and was surprised to find only 20-30 in a typical year. To eliminate random fluctuations due to the low counts, I thus binned the data into decades before plotting the temporal trend (black dots are actual data points, red curve is a quadratic trendline):

The shocking result is that the frequency of Christmas-related papers has steadily dropped to less than half of what it was in the 1950s!

How can this be? I can think of several possibilities, and you are welcome to come with more in the comments:

• We are running out of new funny things to say about Christmas.
• An increasing proportion of researchers come from countries, in which Christmas is not widely celebrated.
• Researchers have collectively stopped believing in Santa, as funding has dried up.

Merry Christmas Everyone!

Resource: You want REST with that GreenMamba?

When you set up a GreenMamba resource, you get not only a web interface for human users, but also a REST web service API meant for scripts to interact with your tool. The REST interface is such an integral part of GreenMamba, that it is not even optional – you get it whether you want it or not. However, since the purpose of setting up GreenMamba resources is to make your tools and databases accessible to others, we cannot think of a good reason why you would not want to expose them as web services when it takes no extra work.

To illustrate how command-line tools can be accessed as web services, we return to the Motifs tool described in an earlier blot post. In addition to having an HTML web interface, it is accessible as a REST web service through the following URL (here shown as a GET request for simplicity; POST requests are also supported):

http://localhost:8080/REST/Motifs?fasta=sequences&
motif=regular expression

The name and parameters for the web service map one-to-one to the resource name and command-line arguments specified in the inifile:

[Motifs]
command : greenmamba/examples/motifs.pl $motif @fasta

GreenMamba also provides a REST web service API around any database that you configure through the inifile, although it is admittedly not as elegant as it could be. However, there is not much need for an API in this case, as the database functionality of GreenMamba is only intended for databases that are so small that they can easily be downloaded in their entirety instead.

In case of a GreenMamba metatool there is not a corresponding web service per se. However, because a metatool is made up of a list of subtools that all have their individual sections in the inifile, each of the underlying tools has a REST web service. All the functionalities of a metatool are thus nonetheless exposed as web services.

It should be noted that the REST web services provided by GreenMamba return the output from the underlying tools as is. It may thus be worthwhile to change (or write a post-processing scripts for) tools so that they produce simple tabular output. This will both make GreenMamba format the output nicer in the HTML web interface and make the REST web services more usable.

Resource: Adding bells & whistles to GreenMamba

My latest blog post ended at the stage where we had combined the Instances database and the Motifs tool into a single metatool. In this post I will show how little it takes to add the bells and whistles that turn it into the complete, professional web resource that I showed as a teaser in the first blog post of this series.

You may not want green to be the design color used throughout your web interface. This is easily changed by adding a line like color : #083D65 to your inifile. You can use named colors instead of hex values if you prefer. Whichever color you pick will be used throughout the web interface to ensure a consistent design.

In the simple default design the frame changes size when changing between the Motifs and Instances input forms because the forms are not equally wide. This can easily be changed by setting a fixed width for all lines by adding line such as width : 650px. You do not have to necessarily specify the width in pixels, any units permitted in cascading style sheets can be used.

Most bioinformatics web resources require one or more pages to explain what the resource is all about. Such pages can easily be provided within the GreenMamb framework a by adding lines with the same syntax as page_home. If you add a page_about line, you will get an ABOUT menu item at the top right, which when clicked will show provided HTML text wrapped with within the GreenMamba layout to provide a consistent look. There is nothing magic to the word “about”; for example, if you write page_download you will get a page named DOWNLOAD.

You may want to also add a footer that is shown at the bottom of every page that, for example, mentions who made the resource, whom to contact in case of scientific questions or technical problems, and possibly points to one or more papers that describe the tools and which the user is requested to cite. To insert a footer you simple add a line to the inifile with the keyword footer followed by the text you want shown; this text can contain HTML code.

If you set up a Mamba server to host a single resource, you will want the Mamba server to automatically direct users to the main input form in case they access the server without requesting a specific page. For example, we would want to redirect requests for localhost:8080 to localhost:8008/HTML/ELM. This can be done the [REWRITE] section in the inifile, which allows you to specify simple URL rewrite rules similar to what can be done in Apache.

Below is the inifile required to set up the complete ELM example resource as it was shown in the first blog post of this series:

[SERVER]
host : localhost
port : 8080
plugins : ./greenmamba

[REWRITE]
/ : /HTML/ELM

[Instances]
database : greenmamba/examples/instances.tsv

[Motifs]
command : greenmamba/examples/motifs.pl $motif @fasta
page_home : greenmamba/examples/motifs_home.html

[ELM]
tools : Motifs; Instances;
color : #083D65
width : 650px
footer : Disclaimer: This is ELM mirror only serves as an example for the GreenMamba framework. For scientific purposes, please use the real ELM server instead.
page_about : greenmamba/examples/elm_about.html

Starting up the Mamba server with this inifile and accessing localhost:8080 yields this interface:

Clicking the ABOUT link will brings up the contents of the file elm_about.html wrapped with the GreenMamba design elements:

In case you want to include pictures or other content on your pages, you do not need a separate web server to host this. Mamba implements a simple web server that you can use for this purpose; all you have to do is to add a www_dir : <directory> in the [SERVER] section of the inifile and place the files you want to serve within the specified directory.

Finally, the output pages of the metatool are also formatted to follow the design specified in the inifile. The header shows the name if the metatool, color matches that of the other pages, the menu with links to the pages is shown, and the footer is included:

Resource: Combining tools and databases into a single GreenMamba web resource

In the four previous blog posts I introduced the GreenMamba framework (download) and showed how it can be used to turn a simple tab-delimited files or command-line tools into web resources with a bare minimum of effort. In this post I will show how easy it is to configure multiple databases or tools to run under the same Mamba server and how to make them accessible as a single web resource.

To illustrate this, I will take the Instances database and the Motifs tool and turn them into a web resource called ELM (the name of the database from which the instance data and motifs were obtained in the first place). The following inifile is all it takes to do so:

[SERVER]
host : localhost
port : 8080
plugins : ./greenmamba

[Instances]
database : greenmamba/examples/instances.tsv

[Motifs]
command : greenmamba/examples/motifs.pl $motif @fasta
page_home : greenmamba/examples/motifs_home.html

[ELM]
tools : Motifs; Instances;

The [SERVER] section is exactly as in all the previous examples, instructing the Mamba server to run on localhost port 8080 and to import the GreenMamba plugin. The [Instances] section configures a simple database called Instances based on the tab-delimited file instances.tsv, and the [Motifs] section configures a web tool called Motifs that runs the Perl script motifs.pl. These two sections are unchanged compared to the previous blog posts and have here simply been put into inifile, which is how one hosts multiple databases or tools under the same Mamba server. The last section, [ELM], is the only new part. It instructs GreenMamba to configure a metatool called ELM that combines the two tools Motifs and Instances.

Starting the Mamba server with this inifile and accessing http://localhost:8080/HTML/ELM yields the following web interface:

As you can see, what used to be a tool called Motifs has now become a tab within the resource ELM that shows the same (customized) input form. Similarly, the database Instances has become a tab within the same resource:

If you press the submit button for Motifs or Instances, you will get output that is formatted as it was when using Motifs and Instances as separate resources, the only change being that the header says ELM. In the next blog post, I will show how the design of GreenMamba web resources can be further customized and how design changes are consistently applied throughout all the individual tools that make up the metatool.

Resource: Improving a GreenMamba web resource with a custom input form

In the previous blog post I showed how you can use GreenMamba (download) to turn a command-line tool into a simplistic web tool with a minimal of effort. Sometimes, however, you will want to put in just a bit more effort and use a custom input form instead of the default one.

The default input page that was automatically created by GreenMamba based on the syntax of the command alone allowed the user to enter a motif in the form of a regular expression:

Suppose we would rather allow the user to select one of the 166 motifs from the ELM database through an input page looking like this:

To achieve this we add on line to the inifile, which instructs GreenMamba to use the custom HTML in the file motifs_home.html instead of the auto-generated input page:

[SERVER]
host : localhost
port : 8080
plugins : ./greenmamba

[Motifs]
command : greenmamba/examples/motifs.pl $motif @fasta
page_home : greenmamba/examples/motifs_home.html

The file motifs_home.html contains the following piece of HTML code (numerous <option> lines for different ELMs replaced with ... for brevity):

Select the Eukaryotic Linear Motif to search:<br />
<select name='motif'>
<option value='[ILV]..[R][VF][GS].'>CLV_MEL_PAP_1</option>
<option value='(.RK)|(RR[^KR])'>CLV_NDR_NDR_1</option>
<option value='R.[RK]R.'>CLV_PCSK_FUR_1</option>
...
</select><br />
<br />
Enter the sequences to be searched in FASTA format:<br/>
<textarea name='fasta' cols='80' rows='20'>&gt;MYB_HUMAN
MARRPRHSIYSSDEDDEDFEMCDHDYDGLLPKSGKRHLGKTRWTREEDEKLKKLVEQNGT
DDWKVIANYLPNRTDVQCQHRWQKVLNPELIKGPWTKEEDQRVIELVQKYGPKRWSVIAK
HLKGRIGKQCRERWHNHLNPEVKKTSWTEEEDRIIYQAHKRLGNRWAEIAKLLPGRTDNA
IKNHWNSTMRRKVEQEGYLQESSKASQPAVATSFQKNSHLMGFAQAPPTAQLPATGQPTV
NNDYSYYHISEAQNVSSHVPYPVALHVNIVNVPQPAAAAIQRHYNDEDPEKEKRIKELEL
LLMSTENELKGQQVLPTQNHTCSYPGWHSTTIADHTRPHGDSAPVSCLGEHHSTPSLPAD
PGSLPEESASPARCMIVHQGTILDNVKNLLEFAETLQFIDSFLNTSSNHENSDLEMPSLT
STPLIGHKLTVTTPFHRDQTVKTQKENTVFRTPAIKRSILESSPRTPTPFKHALAAQEIK
YGPLKMLPQTPSHLVEDLQDVIKQESDESGIVAEFQENGPPLLKKIKQEVESPTDKSGNF
FCSHHWEGDSLNTQLFTQTSPVADAPNILTSSVLMAPASEDEDNVLKAFTVPKNRSLASP
LQPCSSTWEPASCGKMEEQMTSSSQARKYVNAFSARTLVM</textarea>

Note that this is not a complete HTML page but only the piece of HTML code that goes between the <form> and /<form> tags (minus the submit button). Also note that the names of the input fields must match the handles specified under command in the inifile (e.g. fasta and motif; if they do not, GreenMamba will have no idea where to insert the user input in the command.

The example above is unusually complex due to the mapping of ELM names to regular expression. Usually your custom HTML forms will be far shorter. In those cases you may not even want to store the custom HTML file and instead provide the HTML on a single line inside the inifile, which GreenMamba supports.

Finally, it should be pointed out that this customization step is entirely optional. You do not have to edit HTML forms to set up GreenMamba web resources, but you have the flexibility to do so if you want to.

Resource: Turning a command-line tool into a web tool with GreenMamba

In two previous blog posts we introduced the GreenMamba framework (download) and showed how it can be used to easily set up a web database from an Excel sheet or tab-delimited file. However, the primary motivation for developing GreenMamba was to make it as simple as possible to turn command-line tools, e.g. sequence-based prediction methods, into full-fledged web tools.

The work that would normally be required to do so is to install a web server, create an HTML page with an input form, and code a CGI script that receives the input from the form, converts the input data into command-line arguments, executes the command-line tool, and returns the result. This is not terribly difficult provided that you know how to configure a web server (e.g. Apache) and write CGI scripts. However, it takes considerable time to design a consistent, professional looking HTML web interface that handles both input and output and works correctly on all major web browsers.

With GreenMamba setting up a command-line tool as a web tool requires only a few lines in the inifile describing the name and command syntax of the tool. To exemplify this, we have made a simple example Perl script that simply searches a regular expression against a set of protein or DNA sequences in a FASTA file, both of which are provided by the user. The following inifile is all it takes to turn that Perl script into a web tool:

[SERVER]
host : localhost
port : 8080
plugins : ./greenmamba

[Motifs]
command : greenmamba/examples/motifs.pl $motif @fasta

The first two lines should be familiar from the previous blog post, and the last two lines specify that we have a tool called Motifs, which should run the Perl script motifs.pl with two arguments $motif and @fasta. The difference between handles starting with $ and @ is that the former will be replaced with the input data, whereas the latter will be replaced with the name of temporary file containing the input data. In the example, the script is to be run with a regular expression ($motif) as first argument and the name of a fasta file (@fasta) as second argument.

Based on the command-line syntax given in the inifile alone, GreenMamba creates the following rudimentary web interface, which can be accessed through http://localhost:8080/HTML/Motifs (here shown with a query):

The names of the various handles (@fasta and $motif) are used as labels for the input fields. It is thus possible to improve the interface a bit simply by giving the handles more descriptive names (underscores will be shown as spaces). GreenMamba also allows the use of a customized input form, which will be explained in an upcoming blog post.

In this example above, pressing the submit button causes GreenMamba to take the command from the inifile, replace $motif with the content of the motif text field, replace @fasta with the name of a temporary file into which the content of the fasta textarea has been written, and execute the resulting command using a system call. Subsequently the output of the command is read and temporary files deleted. In this particular case, the script produces tab-delimited output, which GreenMamba automatically detects and formats as an HTML table in the output page:

If the output is not tab-delimited, it is by default shown as plain pre-formatted text. However, through the .ini file you can change it to handle several other types of output including comma-separated values, HTML, and several image formats. We will likely add support for more formats in the future.

Resource: Turning an Excel sheet into a web-accessible database with GreenMamba

Anyone who has worked with computational biology for many years will be familiar with the following situation: from collaborators you have received an Excel spreadsheet, which is generously referred to as a “database”, and you now need to make the data accessible to the world. One could obviously simply provide the file for download; however, it would be much preferred if the data could be searched through a simple web interface.

This is not a particularly difficult job, but it is a fair amount of work to do. Typically you would need set up a database (be that an SQL database or something else), write a CGI script that queries the database and formats the result as an HTML table, and spend some time on web design to make the input and output pages look aesthetically pleasing. It all takes a lot of time that you would probably rather spend on doing something more productive. Consequently this is often not done at all, and data sets that might be of value to others are thus never made available.

One of the key features of the GreenMamba project (see previous blog post on the topic) is to make it as easy as possible to turn any regular Excel spreadsheet into a web database with nearly no work involved. In fact, all it takes is the following four steps:

1. Download and unpack Mamba.
2. Save your spreadsheet in tab-delimited format with column names in the first line.
3. Add the following two lines to your .ini file:
   [NameOfDatabase]
database : my_spreadsheet.tsv
4. Start the Mamba server (./mambasrv my_database.ini)

To exemplify this, we downloaded the complete list of 1743 known instances of Eukaryotic Linear Motifs from the ELM database. The following inifile is all it taks to turn the resulting tab-delimited file into a simple web-accessible database:

[SERVER]
host : localhost
port : 8080
plugins : ./greenmamba

[Instances]
database : greenmamba/examples/instances.tsv

The [SERVER] tag specifies the host of the computer where the mamba web server actually runs and the plugins variable specifies where to load the plugins that enable the whole green-mamba framework and should always be set to this to work. The [Instances] tag specifies the name of the database and the database points to the tab-delimited version of the spreadsheet. After starting the mamba server you can access http://localhost:8080/HTML/Instances and to see the following query interface (here shown with a query):

Upon submitting the query, GreenMamba retrieves all lines that match the search criteria and formats them as an output page:

One could set up a nicer and simpler version of the database by filtering the tab-delimited file a bit. For example, one might want to leave out the columns ELMType (which is redundant with ELMIdentifer), Accessions, InstanceLogic, Evidence, PDB, and Organism (which is redundant with ProteinName) and rename ELMIdentifier to ELM and ProteinName to Protein. This would result in a simpler query form and a more concise results table. Doing this is left as an exercise for the interested reader.

Resource: Turning databases and tools into web resources with GreenMamba

Today, the users of bioinformatics databases and tools increasingly rely on being able to access them through web interfaces. Almost all major databases and most of the commonly used tools can be accessed in this manner, which is mostly good news from the users perspective. However, in my experience from teaching on numerous courses, these users have never worked with a command line and thus typically run their head against a wall the moment they have to do anything slightly more specialized than, for example, running a BLAST search or making a multiple alignment.

The reason for this is simple: specialist tools and databases are typically not made available through user-friendly web interfaces, because they have too few users to make it worthwhile to create such an interface. Worse yet, the tools are in many cases not even distributed, because the many dependencies and lack of documentation would result in too many questions if one were to distribute it. Consequently, almost every bioinformatician that I have spoken about this has one or more resources that they are currently not sharing – not because they are not willing to share, but because sharing would imply too much extra work. To address this problem, we have developed a web server that allows you to easily wrap existing databases and tools with a web interface like the one shown below.

In my group we are involved in the development and maintenance of many bioinformatics web resources, and I have thus been pushing the development of a reusable infrastructure. The result of this is the Python framework Mamba, which has primarily been developed by Sune Frankild and myself. Briefly, Mamba is a network-centric, multi-threaded queuing system that deals with the many technical aspects related to network communication with the clients and server-side resource management. All the specific work pertaining to a resource is done by modules that run under the Mamba server. GreenMamba is one such Mamba module, which based on a simple configuration file can provide a complete web interface around a tab-delimited data file or a command-line tool.

It is thus with great pleasure that we can now release the first version of the Mamba queuing system and GreenMamba wrapper under the BSD license. We hope that by eliminating most of the work in setting up bioinformatics web resources, it will encourage people to make available data sets and tools that hitherto were not worthwhile the time and effort to set up.

Over the next days and weeks, I plan to publish a series of blog posts that illustrate how one can use this framework to wrap a web interface around existing databases and command-line tools with practically no work. Impatient people are welcome to download the software and look in the greenmamba/examples directory.

Live: Lecture by Nobel Laurate Avram Hershko

Today I am at the the symposium “Protein Chemistry ‐ Applications to Combat Diseases”, which takes place in Copenhagen a few minutes walk from where I work.

This morning started with a keynote lecture by Nobel Laurate Avram Hershko on regulation of the cell division cycle by ubiquitin‐mediated protein degradation. This post is just a very quick write-up and a few photos made during and immediately after his presentation.

Most of the early work on ubiquitylation was done on model proteins, most of which were extracellular. Interestingly, what spurred Avram Hershko on to study ubiquitylation of physiologically relevant proteins was the early work on cyclin degradation for which Tim Hunt received the Nobel Prize. Tim Hunt speculated speculated that there was a cyclin protease that would break down cyclins. However, Avram Hershko showed in 1991 that cyclins are in fact not degraded by a specific protease, but are rather targeted for proteasomal degradation by a specific ubiquitin ligase. Showed this in JBC papers in 1991 and 1994. One year later his group identified this ubiquitin ligase to be what is now known as the Anaphase Promoting Complex (APC) / Cyclosome (APC/C).

In addition to being crucial for degradation of cyclins, APC/C is also required for entry into anaphase of the cell cycle (hence the name Anaphase Promoting Complex). This because it is responsible for targeting the securin protein for degradation, which in turns releases separase activity to degrade the cohesin rings that hold together sister chromatids.

Having worked on other cell-cycle proteins for many years, Avram Hershko has in recent years returned his interest to APC/C, more specifically to understand how the inhibition of APC/C is released, which in turn leads to the whole series of events described above.

Analysis: Toward doing science

Yesterday, Rangarajan and coworkers published a paper in BMC Bioinformtatics entitled “Toward an interactive article: integrating journals and biological databases”. Not many hours later Neil Saunders made the following tweet commenting on it:

This reminded me of a draft blog post that I wrote in 2008 on the use of the word “toward(s)” in article titles, and I decided that it was time to update the plot and finally publish it. The background was that I had the gut feeling that there was a somewhat disturbing trend, namely that more and more papers use these words in the title. I thus went to Medline and counted the fraction of papers from each year having a title starting with “toward” or “towards” (I also included them if towards appeared inside the title following a colon, semicolon, or dash):

The plot shows that fraction of articles with “toward(s)” in the title is rapidly rising; it has more than tripled over the past two decades. There is thus no doubt that the use of “toward(s)” in article titles is a trend in biomedical publishing.

As is often the case with statistics, though, this analysis answers only one question but leads to several new ones. Are we increasingly selling our papers on what we hope to do soon rather than on what we have actually done? Or have we just become more honest by now adding the word “toward(s)” where we might have left it out in the past?