Výsledky projektu

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Saharak
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Výsledky projektu

#1 Příspěvek od Saharak »

31. Října nás vědecký tým kolem projektu Human Proteome Folding oblažil nejnovějšími informacemi z jejich bádání, tak nemeškejte a okuste svérázný humor vedoucího týmu na vlasní oči.
http://homepages.nyu.edu/~rb133/wcg/thr ... 10_31.html

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Re: Výsledky projektu

#2 Příspěvek od krahulik »

Progress report projektu z listopadu 2009
HPF2 Update November 2009
Greetings WCG Volunteers,

As the first World Community Grid project, we'd like to celebrate the WCG's anniversary with a recap of all the contributions to protein science that your work as made. Over the past few years, WCG volunteers have provided over 50,000 CPU years (as calculated by the WCG) and folded over tens of thousands of protein sequences. Often there is very little known about the sequences we've folded, and WCG protein structure predictions provide the only available annotations for scientists studying these proteins. Biologists from different disciplines have used our structure predictions to make informed decisions about experiments and infer protein functions and molecular processes.
In the early stages of our project, an effort was made to make focused predictions for proteins of interest. The yeast proteome was originally targeted for the vast amount of other experimental data available.

Malmström L, Riffle M., Strauss CEM, Chivian, D, Davis TN., Bonneau R.3 and Baker D. Superfamily Assignments for the Yeast Proteome through Integration of Structure Prediction with the Gene Ontology. PLoS Biol. (2007) Apr;5(4):e76.
We predicted protein structures to further annotate this genome and compliment the array of protein interaction and molecular function information on this heavily studied model organism. Our results confirmed the feasibility of extending our approach to other less studied, larger proteomes.

A cross section of organisms (including Human, Mouse, Fly, E.Coli, Worm, and other unique organisms) have been processed completely, and protein sequences of unknown structure have been folded by the WCG. Our database has grown to include over a million protein sequences, and WCG predictions are complimented by known structures and a host of other structure and sequence metrics. We regularly receive special requests for predictions for proteins of varying kind (including but not limited to those related to HIV infection, the development of Malaria, and particular bacterial enzymatic processes).
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A few high profile uses of our database include:

Bonneau, R, Facciotti, MT, Reiss, DJ, Madar A,, Baliga, NS, et al. A predictive model for transcriptional control of physiology in a free living cell. (2007) Cell. Dec 131:1354-1365.
Here we used our structure predictions to find transcription factors, the proteins that turn on and off genes. These predicted transcription factors proved critical (and accurate) in building the genome wide circuit for this organism. The general application here is environmental bioengineering and systems biology.

Mike Boxem, Zoltan Maliga, Niels J. Klitgord, Na Li, Irma Lemmens, Miyeko Mana, Lorenzo De Lichtervelde, Joram Mul, Diederik van de Peut, Maxime Devos, Nicolas Si-monis, Anne-Lore Schlaitz, Murat Cokol, Muhammed A. Yildirim, Tong Hao, Changyu Fan, Chenwei Lin, Mike Tipsword, Kevin Drew, Matilde Galli, Kahn Rhrissorrakrai, David Drech-sel, David E. Hill, Richard Bonneau, Kristin C. Gunsalus, Frederick P. Roth, Fabio Piano, Jan Tavernier, Sander van den Heuvel, Anthony A. Hyman, Marc Vidal. A Protein Domain-Based Interactome Network for C. elegans Early Embryogenesis. (2008) Cell, 134(3) pp. 534 - 545.
Here our predictions were used to map the boundaries between functional parts of proteins. This allows for a whole new way of looking at how proteins interact and co-function to form a working system that the cell relies on. The general application here is broad, as this describes a dataset all types of biologists will use.
Andersen-Nissen E, Smith KD, Bonneau R, Strong RK, Aderem A. A conserved surface on Toll-like receptor 5 recognizes bacterial flagellin. (2007) J Exp Med. Feb 19;204(2):393-403.
Here we predicted the structure of key immune proteins, resulting in a prediction that allowed us to re-engineer a key imune receptor allowing for a better animal model of innate immune responses (key to figuring out several aspects of our response to bacterial infection). This publication has direct application to immunology and fighting infectious disease.
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Recently, we've been working towards a paper that will describe our new methods, highlight our successes, and publicize the already open access to our database. This year we've received an average of 6,300 unique visitors a month. That's over 200 users a day (including weekends)! With the publication of our new methods we expect a significant increase in exposure and are preparing to provide multiple means of user-friendly access for the sometimes complex data. This will include using BioNetBuilder.

Iliana Avila-Campillo, Kevin Drew, John Lin, David J. Reiss, Richard Bonneau. BioNetBuilder, an automatic network interface. (2007) Bioinformatics. Feb 1;23(3):392-3.

Future work will undoubtedly involve the refinement of our protein structure annotations. We're investigating methods for incorporating evolutionary information into our predictions, and overhauling parts of the pipeline that are outdated. There is significant room for improvement in our methods for selecting native-state conformations from structure predictions and assigning family annotations. With the WCG we've been able to cast a wide net, and now we're interested in the improvement of our algorithms and classifiers. WCG predictions will continue to provide data for our ever improving experiments and value to the scientific community.

Here at the Bonneau Lab, we thank you for your dedication to science and ask that you keep crunching!
--
Patrick Winters
Bonneau Lab
Progress report projektu z cervence 2009
HPF2 Update - July 2009
Greetings WCG Volunteers,

We've been working diligently since the last update to compile results for a grand paper describing the research involving WCG protein simulations. We've been folding proteins on the WCG for awhile now, and a handful of papers have been published utilizing our results; but we haven't yet detailed our methods and results in full. As the summer begins, we will be focusing much of our attention on compiling statistics on the accuracy of our structural classifications and molecular function predictions. After we submit the publication for review we will turn our attentions toward improving access to our database so that our predictions can be intuitively used by the community.

In order to properly categorize the accuracy of our structure predictions, we rely on the expansion of the RCSB Protein Data Bank (http://www.rcsb.org/pdb/) and updates to the manually curated SCOP: Structural Classification of Proteins database (http://scop.mrc-lmb.cam.ac.uk/scop/). We only fold proteins that don't have recognizable sequence homology to proteins in these databases, but unless these structures are eventually solved it would be very difficult for us to understand the quality of our predictions. Occasionally, however, a new protein is submitted to the PDB, classified in a SCOP release, and happens to be identical to something we've folded. With proteins like these we can not only examine the quality of the 3D models predicted, but also the accuracy of our predicted classifications. Much of that work had been finished when the SCOP group released version 1.75 in June. While this means we need to re-run much of our analysis, it also means we have a larger set of samples for our statistics.

As an example, here's a protein whose classification we correctly predicted. The structure folded as work unit "bt386" comes from the organism "Thermotoga maritima MSB8" and is deposited in the PDB as 2nzc.
After we finish this work and submit our publication for review, we'll shift focus towards the database and user interface. We would like to make our data as accessible and user friendly as possible. By integrating our predictions with BioNetBuilder (http://err.bio.nyu.edu/cytoscape/bionetbuilder/), a researcher examining protein interactions in particular processes or developmental cycles in organisms will have access to novel predictions about the character of the proteins in question.

We have a lot of work ahead of us to get together all of the analysis and highlights for the coming publication, but it could not match the collective contribution from the WCG. We'll be working hard to keep the research supported by members relevant and important.
Patrick Winters
Bonneau Lab

Progress report projektu z brezna 2009
HPF2 Update - March 2009
Hello Everyone,
I'd like to give everyone an update on our HPF1/HPF2 progress. I've been working in the Bonneau lab since September of last year and it's taken me awhile to produce my first update; sorry. It's been complicated getting up to speed, but the ball is rolling and I'm working diligently on validating and analyzing all of the great data you are producing. I was a contributor to the WCG long before I imagined I would be involved in one of its projects. I can assure you that my new perspective has helped me appreciate the great contribution to basic research that we are all making.

The HPF project is an ongoing effort to automatically annotate the genomes of organisms that have importance to the human race with predictions about protein structure and function. It's an effort that could never succeed without the massive amount of computing power you all in the WCG are providing. We're continuing to post-process HPF2 protein predictions and grow our database and research tools for biologists. With every "experiment," or organism, folded on the grid, we're expanding our database, growing our resource, and contributing to the great effort to map and understand the functional units of life.

Of particular interest at the moment is the GOS set we recently folded. These proteins come from the J. Craig Venter Institute's Global Ocean Sampling Expedition. You folded groups of proteins from their expedition that have no known sequence similarity to any previously discovered proteins. Although many computational biology methods rely heavily on sequence similarity, our effort to predict meaningful things about these proteins will rely heavily on the protein structure simulations produced on the World Community Grid. In the coming months we'll be combining evolutionary analysis with these predictions, and any discoveries for these novel proteins will be truely exceptional and ground breaking.

In regards to HPF2's higher resolution protein predictions, and specifically with respect to the GOS dataset, we are seeing an increased yield in high quality structure predictions. The extra computation and resolution is paying off, and we are able to make more predictions about proteins confidently. Despite the scale and scope of the project, we really do appreciate each member's contribution. Thanks again for volunteering for HPF!

Patrick Winters
Bonneau Lab
Naposledy upravil(a) krahulik dne pon 28 pro, 2009 12:02, celkem upraveno 1 x.
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