Freelancing science » Papers

Many Eyes and literature summary

Pawel Szczesny — Sat, 04 Oct 2008 16:32:38 +0000

I’m not the first one to come up with this idea – Ntino posted about it before. However, I didn’t really understand before how powerful it could be. Using Many Eyes visualization capabilities I’ve created a quick browsable summary of abstracts related to a particular protein. I took all abstracts PubMed returned for a particular query (in this case it was “YadA Yersinia”; YadA is a prominent adhesin and important pathogenicity factor in Yersiniae) and uploaded them as text into Many Eyes. I chose “Word Tree” representation and searched for “yada”, which gave a nice graph of the most prominent phases related to this protein/gene name. Maybe it’s not a breakthrough, but compared to the classification/semantification provided by GoPubMed, such approach works much better for entities that aren’t well described in biological ontologies.

Given that the whole concept is pretty straightforward, it would be nice if one of alternative PubMed search engines provided a similar method of summarizing user’s query, don’t you think?

Structure of usher pore is available

Pawel Szczesny — Sat, 31 May 2008 17:53:45 +0000

Some time ago I posted breaking news about solved structure of usher pore. And few days ago it was deposited into PDB as 2VQI (publication appeared in Cell, here’s the abstract). The structure is a beatiful dimer (see above) of 24 stranded beta-barrel, the first of its kind. The paper contains also structures of the whole complex reconstructed based on cryo-EM data.

Interestingly, while the structure of the native dimer is symmetrical, the function of the units is not. Both of twinned pores are involved in alternating recruitment of chaperone:pili-subunit complexes, but only one actually transports pili subunits out. Overall, given large amount of detailed studies on the mechanistic properties of pili transport and formation, this is the best understood translocation process at a structural level.

Read the paper and draw your own conclusions, but for me it changes the way of thinking about protein translocation in bacteria. We learnt a lot on bacterial secretion by observing how similar proteins are involved in fundamentally different processes (for example DNA export and toxin secretion may use the same system). Similarly, usher pore is going to serve as an exemplar for newly found translocation elements.

Semi-automated workflows – Taverna Interaction Service

Pawel Szczesny — Wed, 12 Mar 2008 15:56:15 +0000

I was still thinking about recent Neil’s wondering about possibility of automating every scientific workflow, when I saw this (Bioinformatics Advance Access abstract):

The Taverna Interaction Service: enabling manual interaction in workflows by Anders Lanzén and Tom Oinn

Taverna is an application that eases the integration of tools and databases for life science research by the construction of workflows. The Taverna Interaction Service extends the functionality of Taverna by defining human interaction within a workflow and acting as a mediation layer between the automated workflow engine and one or more users.

I have not tried it yet but this Taverna plugin is very likely an answer to doubts I often have when automation of bioinformatics workflows is discussed: we shouldn’t always remove ourselves from the workflow, as interaction with software can be often critical in making a discovery. For example conscious decision about which sequences should go in during PSI-BLAST search can dramatically influence quality of resulting profile. So I agree with Neil that not every workflow can be automated, but more importantly not every workflow should be. Possibility of wrapping one’s mind around a problem is gone when there’s no feedback loop on the process.

Peptide and Protein Building Blocks for Synthetic Biology – EHC Broomley et al.

Pawel Szczesny — Mon, 04 Feb 2008 17:29:36 +0000

With my background in protein sequence analysis and recently increasing interest in synthetic biology/biological engineering, Deepak’s post about BioBrick project immediately caught my eye. However, after spending some time around registry of standard biological parts I realized that using full natural proteins as modules wasn’t very appealing to me. My thoughts oscillated in area between nanotechnology at a atomic level, and BioBrick approach – my idea for “a brick” was something from supersecondary structure elements to protein domains.

While I was trying to figure out what was done in this area, here’s what appeared in Google Reader: Peptide and Protein Building Blocks for Synthetic Biology: From Programming Biomolecules to Self-Organized Biomolecular Systems by E.H.C. Broomley, K. Channon, E. Moutevelis and D.N. Woolfson (DOI: http://dx.doi.org/10.1021/cb700249v). It’s not an open access paper, but you can download it from Dek Woolfson lab page. This review summarizes several different approaches to synthetic biology focusing specifically on peptides and proteins as a prime component of newly engineered machines. Why actually peptides and proteins? Here are some points from the paper:

efficient, reproducible and spontaneous folding with all information usually encoded in the polypeptide chain
organization of the folded structures, including secondary structure elements (referred there as tectons), which naturally limits the possible number of folds, but gives enough different structural scaffolds to display many biological functions
frequently observed self-assembly of folded structures into higher-order complexes/nanomachines

The review gives examples of selected protein folding motifs (like collagens or zinc-fingers) that can be used in designing novel fibrous materials, but describes in great detail various assemblies made of protein coiled-coils.

Being pretty familiar with coiled-coil structures, I was rather more interested in general view on the field – and I wasn’t disappointed. Below I copied first figure from this paper (for its legend see the original paper) – it’s a beautiful breakdown of different methodologies in synthetic biology. You can place on this graph most approaches people are taking in this area (from Venter’s bacteria, through BioBricks, to DNA cubes).

Jane – Journal/Author Name Estimator

Pawel Szczesny — Mon, 28 Jan 2008 11:52:34 +0000

Jane – Journal/Author Name Estimator is a new web based application that can suggest potential reviewers or target journals for a manuscript based on its title and abstract. It was just published by Bioinformatics under Advance Access (but unfortunately it’s not an open access article). I have tested two of my upcoming publications and Jane performed well: I wasn’t surprised by most of predicted names and journal titles. The topic I’m writing about in these papers is rather narrow, so don’t treat it as any performance measure – test it yourself, if you are interested.

Probably I’m not going to use it as authors suggested – I consider this application a helpful literature research tool.

Publishers, please provide images in the journal’s feed

Pawel Szczesny — Tue, 23 Oct 2007 19:45:25 +0000

Currently almost all scientific journals provide a RSS feed of their content. I am very grateful for that, as many other scientists. However, I see a large disproportion between what I would like to scan through and what I’m actually able to. Abstracts, which are usually provided in these feeds, look almost exactly the same, and after thirty or fifty I’m not really sure if I understand what I read (most likely even Robert Scoble would have the same problem, although at a different level). Biochemistry journal found a solution (see below) – providing images instead of abstracts in the feed (in fact, they used this approach on their homepage long before RSS feeds became a standard). It’s simple, very effective and I have no idea at all why it’s not more popular. So here I’m asking – publishers of scientific journals: please give me images in the journal’s feed. I don’t mind having also the abstracts, but visual summary would be much more useful. In return I promise read these feeds instead of relying on Pubmed searches or my colleagues recommendations and GR shared items.

Thoughts on CASP – Critical assessment of methods of protein structure prediction

Pawel Szczesny — Wed, 10 Oct 2007 09:06:24 +0000

I’ve just read an introduction to the supplemental issue of the journal PROTEINS, dedicated to the most recent round of the CASP experiment. It describes the progress of the protein structure prediction over the last few CASP editions.

The list of advancements include:

improvement of the homology modelling: one of the issues in template-based modelling of protein structures was that a final model wasn’t closer to the real structure than a template; now we have statistically significant (although very small) improvement thanks to the multi-template based modelling
fully automated methods are much closer to human predictors than ever: many groups use models from servers as their starting point and usually they don’t improve them that much

I believe that this was possible thanks to the progress that has been made in the area of sequence homology searches. Finding similarity between two sequences well beyond any reasonable identity thresholds is now doable thanks to profile-to-profile comparison, meta-servers (joining predictions from many different methods) or recent hmm-to-hmm algorithms (comparison of Hidden Markov Models). If you can find a suitable template for your protein, the rest is then much easier, isn’t it?

There are of course fields that still need some work. One of these often stirs a lot of discussion: automated assessing of model similarity to the real structure. The current methods have proven their suitability, I definitely agree. However I hope that at some point the protein structure comparison software will refuse to superimpose eight- and ten-stranded beta-barrels or left- and right-handed coiled-coil with a message: “It doesn’t make sense.”

Visualization software for molecular assemblies by Thomas Goddard and Thomas Ferrin

Pawel Szczesny — Sat, 01 Sep 2007 11:02:18 +0000

Recently, among articles “in press” from Current Opinion in Structural Biology I found a paper by Thomas Goddard and Thomas Ferrin about software for visualization of large molecular assemblies. Even if the focus of this paper is not preparation of publication quality pictures, software cited there sounds familiar: Chimera, Pymol, VMD, Qutemol. The authors mention also VISION, which is a visual programming environment capable of presenting molecular data. Molecular Graphics Lab of Scripps Research Institute that works on the VISION has some other interesting tools, including PMV – Python Molecular Viewer, which I hope to cover some other time.

Anyway, this paper actually reminded me of something. I did mention that new version of Chimera can produce input for Povray, but I did not realize that it’s not the only change in this version. After upgrading to the current version I found out that it has also several “presets” of settings suitable for on-screen viewing or producing the figure. That makes preparation of the figure much faster and if you still don’t like the results you get good starting points for some tweaking.

Structure of molecular needle

Pawel Szczesny — Wed, 08 Aug 2007 16:29:16 +0000

After yesterday’s post it’s no secret anymore that I’m interested (among other things) in oligomeric prokaryotic proteins. I often browse recent additions at PDB and see if there’s a new, exciting and pretty (symmetric) structure deposited. A week ago a picture similar to this below drew my attention.

This nice ring of helices is a model of the molecular needle of type III secretion system (T3SS). This system is used by many bacterial species during an infection: attaching to the host cell is followed by a insertion of a needle into the host cell and transporting effector proteins directly into that cell. The model here is a combination of the crystal structure of the single subunit and 3D reconstruction of the needle from electron microscopy.

I believe that next years will bring more full atom models of important cell structures. It can be seen directly from the publications: certain research groups are solving structures of missing elements of the large protein complexes, one by one. The model above is for sure a one step closer to having the whole T3SS, including cytoplasmic, transmembrane and extracellular parts at a atomic resolution.

The paper about this model was published last year in PNAS (free access) by Janet E. Deane and Pietro Roversi et al. The model is deposited in the PDB as 2V6L. PubMed ID for the abstract is: 16888041.