WCGrid News and Talking Points!!

[Arjai]

Microbiome Immunity Project Already Extending the Known Universe of Protein Structures

By: Tomasz Kosciolek, PhD
UC San Diego Center for Microbiome Innovation

7 Mar 2018

Summary
The Microbiome Immunity Project is off to a great start on predicting the structures of hundreds of thousands of bacterial proteins within the human gut. Read about their progress and their plans in their first project update.

Background
The Microbiome Immunity Project was created to better understand the role of the microbiome in intestinal immune response and diseases such as Type 1 Diabetes (T1D) and Inflammatory Bowel Disease (IBD). In this project, we predict structures of bacterial proteins and use this information to annotate their functions and to understand host-microbiome interactions which are responsible for the pathology of IBD and T1D. This is a massive undertaking, as the human gut microbiome has more than 2 million unique proteins, with hundreds of thousands of proteins potentially interacting with human cells. A project of this scale is only possible thanks to the power of World Community Grid.

Our Progress So Far

With your help, we have already predicted the structures of over 50,000 prioritized proteins! In the grand scheme of the 2 million unique bacterial proteins in our gut, this may not seem like a lot, but keep in mind that the experimental work to date covers only approximately 125,000 proteins. In only 6 months we have made tremendous progress by extending our universe of known protein structures by almost 28 percent!

You may have already realized that at this pace, predicting all bacterial protein structures would take years to complete. Fortunately, we don’t have to predict every single structure, because proteins can be grouped into families. These families consist of proteins with similar structures and functions, enabling a comprehensive understanding of the family’s function with only one representative member per family. Once we identify protein families of interest, we will investigate them in more detail.

In the meantime, we have adjusted our strategy on how to prioritize the predictions. Instead of looking only at bacterial genomes (genes of an individual bacterial species), we are investigating bacterial pangenomes (genes of all bacterial strains belonging to the same species)...

We are now extracting information from your predictions, and during the course of the project we plan to make the data available to the public for other exciting research. We are also working on methods to improve predictions of protein functions, enabling us to find the important protein families involved in T1D and IBD among thousands of predictions we have made so far.

All this progress has been made possible thanks to your generous contributions! There is still a lot to discover about the microbiome, but with each computation that you support we are getting a step closer to having a more detailed picture of this important ecosystem inside each of our bodies and understanding IBD and T1D. So, thank you and let’s continue working together on unraveling the mysteries of microbiome!

 

[Arjai]

Drug Search for Leishmaniasis Project Continues Quest for Better Treatments

By: Dr. Carlos Muskus López
Coordinator, Molecular Biology and Computational Unit, PECET University of Antioquia

20 Mar 2018

Summary
The Drug Search for Leishmaniasis researchers recently conducted lab testing on 10 compounds. The testing showed that none of the compounds were good potential treatments, and the researchers will turn their attention to additional compounds.

Short description of the team’s latest findings

Leishmaniasis is one of the most neglected tropical diseases in the world, infecting more than two million people in 98 countries. The current treatments for all forms of leishmaniasis can cause severe side effects, including death. Furthermore, drug resistant parasites are causing major problems in many countries. For these reasons, there is an urgent need for new, safe, and inexpensive drug compounds.

The Drug Search for Leishmaniasis team has continued their lab testing since their last update. The most recent round of testing involved 10 compounds that had been identified as having potential to be safer, more effective treatments.

The compounds were tested first for toxicity, then for effectiveness against two common parasites that can cause leishmaniasis. Based on the testing, none of the compounds tested would be effective treatments for the disease.

Once the team has obtained additional funding, they will test additional compounds that may be useful in treating leishmaniasis.

Anyone interested in a full scientific description of this latest round of testing can read below. Thanks to everyone who supported this project.
In vitro evaluation of the anti-leishmanial activity of predicted molecules by docking

Conclusion

None of the 10 molecules evaluated showed promising anti-leishmanial results based on the in vitro cytotoxicity inhibition assays.

Well, if nothing else, they have narrowed the field some!

I hope they can secure the funding needed to continue the research. Of all the good thing we hear, about these projects, it is refreshing to see that not everything is all rosy. However, it is this type of basic research that is needed and can, often, lead to new discoveries that were not expected.

I want to congratulate them on all the hard work and wish them the best in securing funding for more research.

There is more, mostly scientific stuff, on the WCG site.

​

 

[manofthem]

Drug Search for Leishmaniasis Project Continues Quest for Better Treatments

By: Dr. Carlos Muskus López
Coordinator, Molecular Biology and Computational Unit, PECET University of Antioquia

20 Mar 2018

Summary
The Drug Search for Leishmaniasis researchers recently conducted lab testing on 10 compounds. The testing showed that none of the compounds were good potential treatments, and the researchers will turn their attention to additional compounds.

Short description of the team’s latest findings







Anyone interested in a full scientific description of this latest round of testing can read below. Thanks to everyone who supported this project.
In vitro evaluation of the anti-leishmanial activity of predicted molecules by docking



Well, if nothing else, they have narrowed the field some!

I hope they can secure the funding needed to continue the research. Of all the good thing we hear, about these projects, it is refreshing to see that not everything is all rosy. However, it is this type of basic research that is needed and can, often, lead to new discoveries that were not expected.

I want to congratulate them on all the hard work and wish them the best in securing funding for more research.

There is more, mostly scientific stuff, on the WCG site.

​

Just saw that notice and took a quick gander. does this mean a new project is on the brink? Certainly wouldn't mind that

 

[Arjai]

Help Stop TB Researchers Seek New Team Members

By: Dr. Anna Croft
University of Nottingham, UK

29 Mar 2018

Summary
The Help Stop TB researchers are looking to expand their team as they analyze the large amount of data generated by World Community Grid. Read about their plans in this update.

Background
Tuberculosis remains one the world’s major killers from infectious disease. The World Health Organization announced in a recent report that 6.3 million new cases of TB were reported in 2016, up from 6.1 million in 2015.
Tuberculosis can be difficult to treat because the bacterium which causes the disease has an unusual coating which protects it from many drugs and from a person’s immune system. Among the fats, sugars and proteins in this coat, the TB bacterium contains a type of fatty molecules called mycolic acids. The Help Stop TB (HSTB) project simulates the behavior of these molecules to better understand how they offer protection to the TB bacteria. With the resulting information, scientists may be able to design better ways to attack this protective layer and therefore develop better treatments for this deadly disease.

Congratulations and Changes
Since our last update, we’ve been undergoing further changes to the project team.
Athina Meletiou is now Dr. Athina Meletiou, having successfully passed her PhD viva (oral examination). She has taken up an EU-funded postdoctoral fellowship working on another large data project of one of our colleagues at University of Nottingham, Professor Charles Laughton, “Advanced multiscale simulation of DNA.”
Athina will still be touching base, as we will be preparing publications from her work in the near future. In the meantime, we wish her well with her next step in her career, with many thanks for the hard work she has put into the HSTB project to grow it into the success it has been so far.

The Search for New Team Members
As a result of Athina’s move, we are now actively looking for new team members, especially those with a strong interest in data science, as we now have a significant quantity of data to mine, for which we would love to apply new approaches. We also want to tackle the development of accurate membrane models, now that we have sufficient atomistic data. Applications from suitably qualified chemists, biochemists, mathematicians, engineers, and computer scientists are welcomed, both for PhD-level and postdoctoral posts.

Best of luck to Athina, and to the HSTB team. It is good to see that these projects not onlyhelp us, the public, but also provide meaningful, and gainful, employment for these highly skilled, and learned, people. What concerns me though, is that the pool of potential candidates, for this position, is not getting bigger.

The WHOLE Story, HERE

STEM Education Data and Trends 2014

The share of grade 8 students at or above the proficient level rose by 10 percentage points, to 36%, from 2000 to 2013 (Figure 1-2). Changes between 2000 and 2013 for most groups were in the range of 8–13 percentage points; however, Asians or Pacific Islanders gained 19 percentage points, and 60% of them performed at or above the proficient level in 2013. English language learners gained just 3 percentage points, with only 5% reaching the proficient level in 2013 (Appendix Table 1-2).

The percentage of all students in grade 12 who were at or above the proficient level in 2013 stood at 26%, below that of eighth graders (36%) and fourth graders (42%) (Figure 1-2). Changes between 2005 and 2013 were generally in the range of 2–4 percentage points, and only Asians or Pacific Islanders were moderately near the 50% mark (Appendix Table 1-2).

Chapter 1. Elementary and Secondary Mathematics and Science Education Open/close all chapter tables and charts. Chapter downloads. Print Elementary and Secondary Mathematics and Science Education PDF. Share chapter.

National Science Board
Science & Engineering Indicators 2016
Table 1-4 Mean mathematics literacy assessment scores of 15-year-old students in developed countries, by country: 2012

Score higher than United States' score of 481
Singapore 574
South Korea 554
Japan 536
Switzerland 531
Netherlands 523
Estonia 521
Finland 519
Canada 518
Poland 518
Belgium 515
Germany 514
Austria 506
Australia 504
Ireland 502
Slovenia 501
Denmark 500
New Zealand 500
Czech Republic 499
France 495
United Kingdom 494
Iceland 493
Latvia 491
Luxembourg 490


My point in all of this is, there are smart people left in this world. But the number of them that are able and willing to Study the Sciences, is falling. Especially, in the United States. The NSF has been doing what they can to amend that but, they probably need more money to actually be effective.

I am no expert, on these trends but, I read these charts and see what I see.

 

[Arjai]

What's tech got to do with it? We went to SXSW to talk about how volunteer computing can help save the planet.

20 Apr 2018

Summary
World Community was invited to give two presentations on the power of crowd-sourced computing power at SXSW 2018 in Austin, Texas. See the full presentations, as well as a short video with excerpts from both, in this article.

In this short video, two scientists talk about the crucial issues they're researching: climate change and clean energy. World Community Grid project manager Juan Hindo and software developer Jonathan Armstrong explain the important role of volunteers in accelerating research.

Last year, IBM issued a call for proposals to climate change and environmental researchers, offering them not only World Community Grid supercomputing power, but also data from The Weather Company and storage on IBM Cloud Object Storage. In this video, IBM Distinguished Engineer and Chief Scientist Lloyd Treinish joins Juan and Jonathan to talk about the most pressing issues in climate change, the extent of the climate change science community's technical needs, and the opportunity for the tech community to help.

Dr. Alan Aspuru-Guzik was the lead researcher for the Clean Energy Project, which uncovered a large number of potential new and improved solar cells. In this presentation, Alan gave an overview of the work so far, and talked about his plans for further extending his collaboration with World Community Grid and other organizations.

 

[Arjai]

Announcing Three Winning Climate Change Projects


26 Apr 2018

Summary
After a rigorous review of dozens of applications from all over the world, we're excited to announce the research groups who will receive super-computing power, weather data, and cloud storage from IBM to accelerate climate change science.

As our planet faces the mounting impacts of climate change, scientists are on the front lines of understanding complex consequences and developing solutions.

We've heard from climate change scientists that common bottlenecks they face include limited access to weather data, and insufficient computing power and data storage capacity to accurately simulate the impacts of climate change.

As a result of this call for proposals, we received more than 70 responses from researchers all over the world. We're thrilled to announce the winners of these resources:

Impact of climate change on public health (Emory University, USA)

Impact of atmospheric aerosols on climate change (Far Eastern Federal University, Russia)

Rainfall modeling in Africa (Delft University of Technology, Netherlands)

These proposals were evaluated by IBM scientists and an outside team of experts for scientific merit, potential to contribute to the global community's understanding of specific climate and environmental challenges, and the capacity of the research team to manage a sustained research project. Researchers also agreed, if they received these resources, to abide by our open data policy by publicly releasing the data from their collaboration with us.

In the coming months, we'll be updating everyone as we get ready to launch these projects. In the meantime, current World Community Grid volunteers who want to support these projects as soon as they start can go to the My Projects page to opt in to new projects as they become available.

Fresh Meat, umm,err, I mean, New Projects!!

The Whole article, with more, is HERE.

The resources IBM is providing for these projects:

Supercharged by IBM Resources

Each of these three winning projects will use one or more of these resources:

Crowdsourced computing power

Scientists receive free, 24/7 access to computing power through World Community Grid,...

Weather data

The historical and real-time weather data of The Weather Company, an IBM business, can help scientists advance our understanding of environmental systems and support the design of solutions to prevent, mitigate against, and adapt to climate change.

Cloud storage

For scientists who work on environmental research initiatives with very large data sets, IBM Cloud Object Storage provides a scalable platform to store and analyze the results of virtual experiments on World Community Grid and conduct further investigations.

More about these resources, HERE

 

[Boatvan]

Fresh Meat, umm,err, I mean, New Projects!!

My takeaway from this post

 

[Arjai]

FightAIDS@Home – Phase 2 Prepares for A New Stage


By: The FightAIDS@Home research team

22 May 2018

Summary
The FightAIDS@Home – Phase 2 researchers are making plans to write a paper and to test new compounds as part of the continuing search for new and better treatments.

Background

...UNAIDS estimates that 36.7 million people were living with HIV in 2016. And while AIDS-related deaths have decreased significantly since their peak in 2005, approximately 1 million people died of causes related to AIDS in 2016. (See the UNAIDS website for more statistics.)

HIV continues to be a challenge because it quickly mutates in ways that make existing drug treatments ineffective. FightAIDS@Home joined World Community Grid more than a decade ago with the simple but challenging goal of finding new treatments for HIV. During Phase 1 of the project, the team identified thousands of potentially promising candidates to be confirmed experimentally in the lab. However, because it’s cost and time prohibitive to lab test all the potential candidates, Phase 2 was created to prioritize the candidate compounds by evaluating them with more accurate methods.

Current Work

Our team is processing the current type of work units through World Community Grid as quickly as possible. Once these work units are completed, we plan to write a paper about the process, including its strengths, limitations, and lessons learned.

We are also planning to use World Community Grid’s computing power to analyze new compounds that are important to our work with the HIVE Center at the Scripps Research Institute. This work will begin after we run a sample of these new compounds on our own grid computing network.

Another new Project, on it's way!

Thank You
We appreciate everyone who continues to donate their computing power to the search for better anti-HIV treatments. We also encourage everyone to opt in to Phase 2 of the project—the more quickly we can run through the current work units, the sooner we can move ahead to new compounds.

Always good news to see progress and the opportunity to help with new project discoveries!

A little more info, HERE

Release Notes for BOINC 7.8

Changes in 7.8.5
(Mac only release)
Mac screensaver: under OS 10.13+ if the BOINC screensaver cannot display a graphics app with hardware acceleration using the IOSurface APIs because the app has not been linked with the current graphics libraries, then display it using the much slower CGWindowListCreateImage API.

If you are crunching on a Macintosh, this is for YOU! Otherwise, us PC user's are fine!

 

[Arjai]

Updates to World Community Grid Policies and Options for Data Protection


25 May 2018

Summary

We have updated our Online Privacy Statement and Terms of Use, and are introducing new features to give World Community Grid volunteers more control over their data.

A few of the major changes are listed below. You can read our updated Online Privacy Statement and Terms of Use for more details.

The changes go into effect as of May 25, 2018. Thanks to all volunteers for your continued support and participation.

More details in the links above and HERE on the WCG post

 

[Arjai]

Planned Maintenance on Monday, June 4

31 May 2018

Summary
We are updating the operating system on our servers on Monday, June 4, beginning at 15:00 UTC.

We will be applying an important operating system update to our servers on Monday, June 4, beginning at 15:00 UTC. We anticipate that the work will take approximately four hours.

During this time, volunteers will not be able to upload or download new work, and the website will not be accessible. No action is required by you, as your devices will automatically retry their connections after the maintenance work is completed.

We appreciate your patience and participation.

 

[Arjai]

Smash Childhood Cancer Researchers Choose New Target Molecules


By: Dr. Akira Nakagawara, MD, PhD
CEO of the Saga Medical Center KOSEIKAN and President Emeritus, Chiba Cancer Center

5 Jun 2018

Summary
The Smash Childhood Cancer research team recently chose several new target molecules as the focus of their current work. Learn more about the significance of these molecules in this update.

Almost a year and a half has passed since we kicked off the Smash Childhood Cancer project. On behalf of all the team members, I really appreciate volunteers' contributions to this project.

By adding new members to the original group from the Help Fight Childhood Cancer project, our research team for Smash Childhood Cancer has become quite international, with pediatricians from Japan, Hong Kong, and the United States involved in this big, new drug development project.

While the Help Fight Childhood Cancer project's goal was to search for new and better treatments for neuroblastoma, Smash Childhood Cancer addresses not only neuroblastoma, but other childhood cancers such as brain tumors, osteosarcoma (bone cancer), germ cell tumors, hepatoblastoma (liver cancer), and others.

Several proteins--beta-catenin, LIN28B , N-CYM and others--have been newly chosen as target molecules....

The N-CYM protein, which was discovered by my team and myself, is the novel driving gene product of neuroblastoma. The protein is only found in humans and chimpanzees, and is created through de novo evolution (meaning it is part of the evolution of the cancer). The protein is quite difficult to crystallize for some reason and we are still working on determining its exact structure so that drug discovery against it could begin.

Recently, we received a grant from Japanese government to support our drug discovery against the LIN28B protein, which may help accelerate our progress on Smash Childhood Cancer.

Once again, I would like to express our gratitude for volunteers all over the world who have been supporting the project. For children who are fighting childhood cancer, we would like to discover a new drug as soon as possible and develop a treatment without subsequent side effects.

A little more, HERE

 

[Arjai]

Release Notes for BOINC 7.10

Changes in 7.10.3

(Mac only release)

• Patch wxWidgets 3.1.0 to fix BOINC Manager crash on OS 10.6

Changes in 7.10.2

• MGR: don't crash if GUI RPC returns empty reply
• MGR: use "client" instead of "daemon"
• MGR: Rename OK button to Save button
• MGR: remove excess blank lines in notices
• client: fix bug where client does tight loop if no_gui_rpc set
• client, MGR: add auto-login
• MGR: don't show Attach Wizard at startup if autologin in progress
• client: make autologin work for account managers as well as projects
• Mac client: Fix bug which caused BOINC client built with SDK OS 10.11 or later to fail to get correct system RAM size when running on older versions of OS X
• Mac client: fix a bug which caused the BOINC client to crash immediately on launch under OS X versions OS 10.11 and earlier
• client: update ca-bundle.crt to latest copy of certificates
• boinccmd: show CPU/GPU resources in --get_task
• Update all_projects_list.xml file.
• Linux: Default working directory changed to /var/lib/boinc
• Show build not OS platform in messages

BOINC 7.10 now compatible with Domain Controllers

Since BOINC 7.6.1 the test whether BOINC is being installed on a domain controller no longer returns an error. In the past the installer would make BOINC limited user accounts for the client to run with whether you installed as a user installation or as a service installation.
Since some time now these limited user accounts only get installed when BOINC is installed as a service, no longer on user installations. Because these limited user accounts were a problem for DCs that run with a global user account, you can install the new client and see that it now works. Do make sure to install as the user install, not as a service. (It may be that the service install is disabled, we'd like to get feedback on that.)
Note: do know that when you only allow BOINC to do work when no one is logged on, that this only works with the service installation. Using the user installation will only allow BOINC to do work when someone is logged in.
For all changes, fixes and additions, see the BOINC Version History.
Known Issues

The following issues are already known to the developers:
Windows

Service Installation, GPU detection and Windows XP: Due to problems with up-to-date GPU drivers causing BOINC to crash or hang, it was decided that for all versions of Windows the GPU detection will no longer work when BOINC is installed as a service. This may change in a future version, but only after the GPU manufacturers have adjusted their driver code. So even in Windows 2000 and XP you can now no longer install BOINC as a service yet still have it detect your GPU(s) and run work on it. This change is present since 6.12.38

In it's entirety. Sure don't know the difference between user install and a service install. I guess I don't really care, at this point. Since, I also don't know what a Domain Controller is, I am probably immune from the update.

It also mentions something about moving directories in Linux. Not sure this would benefit my Linux boxes, or not, since they seem to be running just fine.

Download it HERE

 

[Arjai]

Microbiome Immunity Project Researchers Create Ambitious Plans for Data


By: Dr. Tomasz Kościółek and Bryn Taylor
University of California San Diego

19 Jun 2018

Summary
The Microbiome Immunity Project researchers—from Boston, New York, and San Diego—met in person a few weeks ago to make plans that include a 3D map of the protein universe and other far-ranging uses for the data from the project.

The research team members pictured above are (from left to right): Vladimir Gligorijevic (Simons Foundation’s Flatiron Institute), Tommi Vatanen (Broad Institute of MIT and Harvard), Tomasz Kosciolek (University of California San Diego), Rob Knight (University of California San Diego), Rich Bonneau (Simons Foundation’s Flatiron Institute), Doug Renfrew (Simons Foundation’s Flatiron Institute), Bryn Taylor (University of California San Diego), Julia Koehler Leman (Simons Foundation’s Flatiron Institute). Visit the project's Research Participants page for additional team members.
​

During the week of May 28, researchers from all Microbiome Immunity Project (MIP) institutions (University of California San Diego, Broad Institute of MIT and Harvard, and the Simons Foundation’s Flatiron Institute) met in San Diego to discuss updates on the project and plan future work.
Our technical discussions included a complete overview of the practical aspects of the project, including data preparation, pre-processing, grid computations, and post-processing on our machines.

We were excited to notice that if we keep the current momentum of producing new structures for the project, we will double the universe of known protein structures (compared to the Protein Data Bank) by mid-2019! We also planned how to extract the most useful information from our data, store it effectively for future use, and extend our exploration strategies.

We outlined three major areas we want to focus on over the next six months.

Structure-Aided Function Predictions

We can use the structures of proteins to gain insight into protein function—or what the proteins actually do. Building on research from MIP co-principal investigator Richard Bonneau’s lab, we will extend their state-of-the-art algorithms to predict protein function using structural models generated through MIP. Using this new methodology based on deep learning, akin to the artificial intelligence algorithms of IBM, we hope to see improvements over more simplistic methods and provide interesting examples from the microbiome (e.g., discover new genes creating antibiotic resistance).

Map of the Protein Universe

Together we produce hundreds of high-quality protein models every month! To help researchers navigate this ever-growing space, we need to put them into perspective of what we already know about protein structures and create a 3D map of the “protein universe.” This map will illustrate how the MIP has eliminated the “dark matter” from this space one structure at a time. It will also be made available as a resource for other researchers to explore interactively.

Structural and Functional Landscape of the Human Gut Microbiome

We want to show what is currently known about the gut microbiome in terms of functional annotations and how our function prediction methods can help us bridge the gap in understanding of gene functions. Specifically, we want to follow up with examples from early childhood microbiome cohorts (relevant to Type-1 diabetes, or T1D) and discuss how our methodology can help us to better understand T1D and inflammatory bowel disease.

The future of the Microbiome Immunity Project is really exciting, thanks to everyone who makes our research possible. Together we are making meaningful contributions to not one, but many scientific problems!

Exciting! I hope to see more from this team! Wouldn't it be nice to rid ourselves of Diabetes!!!



It is all here in this post. The original WCG post is HERE.

 

[Arjai]

Planned Maintenance on Tuesday, June 26


25 Jun 2018

Summary
We are updating the operating system on our servers on Tuesday, June 26, beginning at 18:00 UTC.


We will be applying an important operating system update to our servers on Tuesday, June 26, beginning at 18:00 UTC. We anticipate that the work will take approximately four hours.

During this time, volunteers will not be able to upload or download new work, and the World Community Grid website will not be accessible. No action is required by you, as your devices will automatically retry their connections after the maintenance work is completed.

We appreciate your patience and participation.

 

[Arjai]

Data from Help Cure Muscular Dystrophy Project Helps Shed Light on the Mysteries of Protein Interactions


By: Dr. Alessandra Carbone
Sorbonne Université

26 Jun 2018

Summary

Protein-protein interactions are the basis of cellular structure and function, and understanding these interactions is key to understanding cell life itself. Dr. Alessandra Carbone and her team continue to analyze data on these interactions from the Help Cure Muscular Dystrophy project, and they recently published a new paper to contribute to the body of knowledge in this field.

In the video above, Dr. Alessandra Carbone gave an overview of the Help Cure Muscular Dystrophy project and its work as of 2014. Since that time, she and her team have published several papers using the project data, including the paper described in this update.
​

Dr. Alessandra Carbone (principal investigator of the Help Cure Muscular Dystrophy project) and team have published a paper entitled "Hidden partners: Using cross-docking calculations to predict binding sites for proteins with multiple interactions" in the journal Proteins.

Protein interactions are the basis for most biological functions. How they interact with each other and other compounds (such as DNA, RNA, and ligands) in the cell is key to understanding life and disease functions. Complicating things, proteins often interact with more than one other kind of protein. To better understand protein functions, tools are required to uncover these potential interactions.

Different parts (surfaces) of the protein can be binding sites that attract another protein. This paper describes a methodology the research team developed to better predict these alternative binding sites. A subset of the Help Cure Muscular Dystrophy project data was used to validate their technique, which will be subsequently applied to the whole dataset computed via World Community Grid.

RESEARCH ARTICLE
Hidden partners: Using cross‐docking calculations to predict binding sites for proteins with multiple interactions

Nathalie Lagarde

Alessandra Carbone

Sophie Sacquin‐Mora

First published: 17 April 2018

https://doi.org/10.1002/prot.25506

Abstract

Protein‐protein interactions control a large range of biological processes and their identification is essential to understand the underlying biological mechanisms. To complement experimental approaches, in silico methods are available to investigate protein‐protein interactions. Cross‐docking methods, in particular, can be used to predict protein binding sites. However, proteins can eract with numerous partners and can present multiple binding sites on their surface, which may alter the binding site prediction quality

For the large majority of these proteins, we show that the predicted alternate binding sites correspond to interaction sites with hidden partners, that is, partners not included in the original cross‐docking dataset. Among those new partners, we find proteins, but also nucleic acid molecules. Finally, for proteins with multiple binding sites on their surface, we investigated the structural determinants associated with the binding sites the most targeted by the docking partners.

Full Published Paper, available for rent or purchase, HERE

Full WCG story, copied here, can be found HERE

This is a lot to wrap my head around but, I must confess, I listened to all 29 minutes of the video. I am sure I could eventually glean more from this video, but I found myself distracted by Alessandra's voice. As I've mentioned before, I have a bit of a crush on Dr. Carbone. She actually has such a great grasp on this subject, she can colloquially explain it, in English, beautifully.

Of course, aside from my musings, this is a VERY important step in Biological study. I can't possibly explain this importance but, I do know that what Dr. Carbone, and her team, are doing will have a great effect on the future of Genetic Disease's.

 

[Arjai]

The Expanding Frontiers of Carbon Nanotube Technology

3 Jul 2018

Summary
The Clean Water Project made an exciting discovery about the possible applications of carbon nanostructures to water purification, biomedical research, and energy research. Dr. Ming Ma, one of the scientists on the project, recently published a paper that summarizes the current status of work in this field.

​

Dr. Ming Ma (of the Computing for Clean Water project) at Tsinghua University recently published a paper in the Journal of Micromechanics and Microengineering entitled "Carbon nanostructure based mechano-nanofluidics." The paper is a thorough survey of all the recent research work on fluid flow in carbon nanostructures, such as carbon nanotubes and graphene sheets.

Carbon atoms can form single-atom thick sheets known as graphene. When these are rolled into tube shape, they are called carbon nanotubes....By using World Community Grid to simulate water flow through carbon nanotubes at an unprecedented level of detail, the project's research team discovered that under specific conditions, certain kinds of natural vibrations of atoms inside the nanotubes can lead to a 300% increased rate of diffusion (a kind of flow) of water through the nanotubes.

There is much research being conducted to understand how this happens and ultimately how to make best use of this property to potentially purify water, desalinate water, and meet other goals in biomedical and energy research.

You can read the paper at http://iopscience.iop.org/article/10.1088/1361-6439/aaa782.

Thanks to everyone who supported this project.

More of the story, HERE.

 

[Arjai]

Planned Maintenance on Tuesday, July 10

5 Jul 2018

Summary
We are updating the operating system on our servers on Tuesday, July 10, beginning at 14:00 UTC.

We will be applying an important operating system update to our servers on Tuesday, July 10, beginning at 14:00 UTC. We anticipate that the work will take approximately four hours.

During this time, volunteers will not be able to upload or download new work, and the World Community Grid website will not be accessible. No action is required by you, as your devices will automatically retry their connections after the maintenance work is completed.

We appreciate your patience and participation.

 

[phill]

I'll remember to look here in future if I have connection issues!!

Thanks for the post @Arjai Thanks to @Norton for pointing it out!!

 

[phill]

It appears that Free-DC is down for the moment, not sure what is happening but can't seem to get any stats for the day at the moment

 

[Arjai]

Farewell and Hello to OpenZika Team Members


By: The OpenZika research team
1 Aug 2018

Summary
The data analysis continues while the OpenZika team bids farewell to one of the project co-investigators and brings on new team members.

Project Background

A change in roles

Dr. Alexander Perryman will be leaving the OpenZika team. In mid-August, Dr. Perryman will become a Senior Scientist II at Repare Therapeutics, a start-up pharmaceutical company in Montreal, Quebec, Canada, that focuses on drug discovery for cancer.

A fond farewell from Dr. Perryman

“I have been working with the IBM team on different World Community Grid projects for almost a decade. Starting with FightAIDS@Home, followed by GO Fight Against Malaria, and for the last two years with OpenZika, it has been a pleasure and a profound privilege to work with the IBM team, the project scientists, and the volunteers who donate their computer power to advance these projects that combat infectious diseases. Although I will be switching from academia to industry, and from infectious diseases to cancer, I will keep focusing on advancing the discovery of drugs that can make a significant impact by reducing suffering and improving human health. The OpenZika team will keep on fighting this good fight without me, and I am confident that progress against the Zika virus will continue to be made. I wish them well, and I thank all of you for your tremendous support during this last decade.”

How job creation and data analysis will be handled going forward
Dr. Melina Mottin, a research associate on the OpenZika team, has been trained by Dr. Perryman, and she will be in charge of the data analysis. She is also going to handle the file preparation to “feed the beast” (that is, to keep creating the docking jobs that you all crunch for us).

Plans for Melina to visit Sean's lab

New candidate inhibitors were recently discovered

In the figure above (created by Dr. Perryman), H-bond signifies hydrogen bonds (a key type of interaction that drives both the strength of binding and the specificity of binding to only the target that you want it to hit). In the image on the bottom right-hand corner, the spheres depict the results of AutoLigand calculations, which detect binding sites and characterize the “hot spots” that give the tightest binding. Green spheres represent hydrophobic interactions in the allosteric site, red spheres depict hydrogen bond acceptors, and blue spheres signify hydrogen bond donors.
​

Upcoming publications

One is a keynote review paper, “The A-Z of Zika drug discovery”, to be published in the journal Drug Discovery Today. The online version of this paper is now available here.

The other paper, “Computational drug discovery for the Zika virus”, will be published soon in a special issue of the Brazilian Journal of Pharmaceutical Sciences. In this paper, we summarize current computational drug discovery efforts and their applicability to the discovery of anti-ZIKV drugs.

In addition, Dr. Perryman, Dr. Ekins, and Dr. Joel Freundlich recently published the paper “Naïve Bayesian Models for Vero Cell Cytotoxicity” in the journal Pharmaceutical Research. (Read the paper here.)

Moreover, the OpenZika project results will be presented at the 256th ACS National Meeting, on August 19-23, 2018, in Boston, MA, USA. Dr. Melina Mottin will be giving an oral presentation and presenting a poster titled “OpenZika: Discovery of new antiviral candidates against Zika virus”, in the session Chemoinformatics Approaches to Enhance Drug Discovery Based on Natural Products.

Past publications and outreach

New collaborations

New students
Dr. Andrade has hired a new graduate student, Bruna Souza, to work in the OpenZika project. She started working on Dr. Andrade’s lab in March 2018, and she is very enthusiastic about learning and collaborating with the project.

Status of the calculations
In total, we have submitted almost 5 billion docking jobs, which involved 427 different target sites. Our initial screens used an older library of 6 million commercially available compounds, and our current experiments use a newer library of 30.2 million compounds. We have already received approximately 4.6 billion of these results on our server.

Thus far, the more than 80,000 volunteers who have donated their spare computing power to OpenZika have given us more than 51,471 CPU years’ worth of docking calculations, at a current average of 64.5 CPU years per day! Thank you all very much for your help!

Fundraising

"We are very grateful for all the volunteers who are donating their unused computing time to this project! Thank you very much!"

More of this Post, much more, can be found HERE.

 

[Arjai]

Planned Maintenance on Tuesday, August 21


15 Aug 2018

Summary
We are updating the operating system on our servers on Tuesday, August 21, beginning at 14:00 UTC.

We will be applying an important operating system update to our servers on Tuesday, August 21, beginning at 14:00 UTC. We anticipate that the work will take approximately four hours.
During this time, volunteers will not be able to upload or download new work, and the website will not be accessible.
Volunteers will not need to take any particular action, as your devices will automatically retry their connections after the maintenance work is completed.
We appreciate your patience and participation.

 

[phill]

I wonder if it's Windows 10 I mean... Server 2016

 

[Arjai]

Sarcoma Dataset Coming Soon to Mapping Cancer Markers Project


By: Dr. Igor Jurisica
Krembil Research Institute, University Health Network, Toronto
8 Aug 2018

Summary
In this comprehensive update, the Mapping Cancer Markers team explains how they are determining which genes and gene signatures carry the greatest promise for lung cancer diagnosis. They also introduce the next type of cancer--sarcoma--to be added soon to the project.

The Mapping Cancer Markers (MCM) project continues to process work units for the ovarian cancer dataset. As we accumulate these outcomes, we continue to analyze MCM results from the lung cancer dataset. In this update, we discuss preliminary findings from this analysis. In addition, we introduce the sarcoma dataset that will be our focus in the next stage.

Patterns of gene-family biomarkers in lung cancer
In cancer, and human biology in general, multiple groups of biomarkers (genes, protein, microRNAs, etc.) can have similar patterns of activity and thus clinical utility, helping diagnosis, prognosis or predicting treatment outcome. For each cancer subtype, one could find large number of such groups of biomarkers, each having similar predictive power; yet current statistical and AI-based methods identify only one from a given data set.
We have two primary goals in MCM: 1) to find good groups of biomarkers for the cancers we study, and 2) to identify how and why these biomarkers form useful groups, so we can build a heuristic approach that will find such groups for any disease without needing months of computation on World Community Grid. The first goal will give us not only information that after validation may be useful in clinical practice, but importantly, it will generate data that we will use to validate our heuristics.

Multiple groups of biomarkers exist primarily due to the redundancy and complex wiring of the biological system. For example, the highly interconnected human protein-protein interaction network enables us to see how individual proteins perform diverse molecular functions and together contribute to a specific biological process, as shown above in Illustration 1. Many of these interactions change between healthy and disease states, which in turn affects the functions these proteins carry. Through these analyses, we aim to build models of these processes that in turn could be used to design new therapeutic approaches.

...However, using these groups of biomarkers for patient stratification may not be straightforward. Groups of biomarkers often do not validate in new patient cohorts or when measured by different biological assays, and there are thousands of possible combinations to consider....

At the present time, there is no effective approach to find all good groups of biomarkers necessary to achieve the defined goal, such as accurately predicting patient risk or response to treatment.

The first goal of the Mapping Cancer Markers project is to gain a deeper understanding of the “rules” of why and how proteins interact and can be combined to form a group of biomarkers, which is essential to understanding their role and applicability. Therefore, we are using the unique computational resource of World Community Grid to systematically survey the landscape of useful groups of biomarkers for multiple cancers and purposes (diagnosis and prognosis).

The combination of this clustering and the World Community Grid patterns enables us to identify generalized gene clusters that provide deeper insights to the molecular background of cancers, and give rise to more reliable groups of gene biomarkers for cancer detection and prognosis.
Currently, we are focusing on the first-phase results from the lung cancer dataset, which focused on a systematic exploration of the entire space of potential fixed-length groups of biomarkers.

As depicted above in Illustration 2, World Community Grid computed about 10 billion randomly selected groups of biomarkers, to help us understand the distribution of which group sizes and biomarker combinations perform well, which in turn we will use to validate heuristic approaches. Analysis showed that about 45 million groups of biomarkers had a high predictive power and passed the quality threshold. This evaluation gives us a detailed and systematic picture of which genes and gene groups carry the most valuable information for lung cancer diagnosis.

To find the appropriate clustering algorithms and the right number of gene groups (clusters) we use different measures to evaluate the quality of each of the individual clustering. For instance, Illustration 3 (above) shows the results of the evaluation of the hierarchical clustering for different numbers of clusters. To evaluate clustering quality, we used silhouette value (method for assessing consistency within clusters of data, i.e., measure of how well each object relates to its own cluster compared to other clusters). A high silhouette value indicates good clustering configuration, and the figure shows a large increase in the silhouette value at 700 gene groups. Since this indicates a significant increase in quality, we subsequently select this clustering for further analysis.

...Since some gene-pattern-families are likely to occur even at random, we use enrichment analysis to ensure the selection only contains families that occur significantly more often than random.
In the subsequent step we validated the selected generalized gene-pattern-families using an independent set of 28 lung cancer data sets. Each of these studies report one or several groups of biomarkers of up- or down-regulated genes that are indicative for lung cancer.

​

Illustration 4 depicts a selection of the most prevalent pattern families and the studies that support them. Each circle in the figure indicates the strength of the support: The size of the circle represents the number of clusters in the family that where found significantly more often in the biomarker of this study. The color of the circle indicates the average significance calculated for all clusters in the pattern-family.

​

Finally, we annotated the most effective gene-pattern-families and their gene clusters with molecular functions and pathways that the genes or corresponding proteins are involved in. Illustration 5 shows an example for such a gene-pattern-family that comprises gene-clusters 7, 1 and 21.

This next quote is the business!

The word cloud visualization indicates that cluster 7 is involved in pathways related to GPCRs (G protein–coupled receptor) and NHRs (nuclear hormone receptors). In contrast, the genes in cluster 1 are highly enriched in EGFR1 (epidermal growth factor receptor) as well as translational regulation pathways. Mutations affecting the expression of EGFR1, a transmembrane protein, have shown to result in different types of cancer, and in particular lung cancer (as we have shown earlier, e.g., (Petschnigg et al., J Mol Biol 2017; Petschnigg et al., Nat Methods 2014)). The aberrations increase the kinase activity of EGFR1, leading to hyperactivation of downstream pro-survival signaling pathways and a subsequent uncontrolled cell division. The discovery of EGFR1 initiated the development of therapeutic approaches against various cancer types including lung cancer. The third group of genes are common targets of microRNAs. Cluster 21 indicates strong involvement with microRNAs, as we and others have shown before (Tokar et al., Oncotarget 2018; Becker-Santos et al., J Pathology, 2016; Cinegaglia et al., Oncotarget 2016).

​

The final illustration evaluates the 20 most significantly enriched pathways for cluster 1. The size of the pathway nodes corresponds to the number of involved genes, and the width of the edges corresponds the number genes of overlapping between pathways. One can see that all pathways involved in translation are highly overlapping. mRNA-related pathways form another highly connected component in the graph. The EGFR1 pathway is strongly overlapping with many of the other pathways, indicating that genes that are affected by those pathways are involved in a similar molecular mechanism.

Sarcoma
After lung and ovarian cancers, next we will focus on sarcoma. Sarcomas are a heterogeneous group of malignant tumors that are relatively rare. They are typically categorized according to the morphology and type of connective tissues that they arise in, including fat, muscle, blood vessels, deep skin tissues, nerves, bones and cartilage, which comprises less than 10% of all malignancies (Jain 2010). Sarcomas can occur anywhere in the human body, from head to foot, can develop in patients of any age including children, and often vary in aggressiveness, even within the same organ or tissue subtype (Honore 2015). This suggests that a histological description by organ and tissue type is neither sufficient for categorization of the disease nor does it help in selecting the most optimal treatment.

Diagnosing sarcomas poses a particular dilemma, not only due to their rarity, but also due to their diversity, with more than 70 histological subtypes, and our insufficient understanding of the molecular characteristics of these subtypes (Jain 2010).
Therefore, recent research studies focused on molecular classifications of sarcomas based on genetic alterations, such as fusion genes or oncogenic mutations. While research achieved major developments in local control/limb salvage, the survival rate for “high-risk” soft tissue sarcomas (STSs) has not improved significantly, especially in patients with a large, deep, high-grade sarcoma (stage III) (Kane III 2018).

For these reasons, in the next phase of World Community Grid analysis, we will focus on the evaluation of the genomic background of sarcoma. We will utilize different sequencing information and technologies to gain a broader knowledge between the different levels of genetic aberrations and the regulational implications.

We will provide a more detailed description of the data and the incentives in the next update.

MORE detailed description? Really?

Other news
We have secured a major funding from Ontario Government for our research: The Next Generation Signalling Biology Platform. The main goal of the project is developing novel integrated analytical platform and workflow for precision medicine. This project will create an internationally accessible resource that unifies different types of biological data, including personal health information—unlocking its full potential and making it more usable for research across the health continuum: from genes and proteins to pathways, drugs and humans.

"Thank you
This work would not be possible without the participation of World Community Grid Members. Thank you for generously contributing CPU cycles, and for your interest in this and other World Community Grid projects."

More of the DETAILS and bib. sheet are HERE

The upshot of it all? Progress is being made, step by step, with the help of US cruncher's crunching the figures, that are saturating them with the info to use their knowledge to untangle this killer and it's many forms.

I love what we can do, working together! WCG is 'da BOMB, Yo!!!

 

[Arjai]

BOINC Developers and Leaders Gather in the UK

30 Aug 2018

Summary
This year's annual BOINC Workshop was held at University of Oxford and focused on the BOINC platform's future development.

​

The Oxford e-Research Centre at University of Oxford recently hosted the BOINC Workshop 2018.

BOINC, which stands for Berkeley Open Infrastructure for Network Computing, is an open-source software platform that supports volunteer computing. You can learn more about how BOINC is structured here.

World Community Grid project manager Juan Hindo, and technical team members Kevin Reed and Keith Uplinger, represented World Community Grid at the event.

This year's workshop included topics such as:

• How the new GDPR regulations may affect BOINC projects
• 
  
• BOINC's technical development over the past year
• Discussion of BOINC review, testing, and release processes
• Overview of current BOINC projects
• An open discussion on working together for the betterment of BOINC

Kevin Reed, who serves as Chairman of the BOINC Project Management Committee (PMC), gave a presentation on the development of the BOINC community.

Keith Uplinger, Secretary of the BOINC PMC, discussed Google Test (a unit testing library for C++).

Juan Hindo gave the group an overview of World Community Grid to the group.

You can see all of the presentations from the workshop here, and listen to audio from the conference here.

Original Story, HERE

 

[Arjai]

THOR Challenge Aims for New Heights in 2018

17 Sep 2018

Summary
CRUNCHERS SANS FRONTIERES, one of World Community Grid's most dedicated teams, issues the THOR Challenge each fall. Find out how you and your team can join this year's challenge and beat last year's results.

​

Every fall, the CRUNCHERS SANS FRONTIERES team begins a new school year by issuing the THOR Challenge (between September 24 and November 11 for 2018). The first week of this team challenge is open to every World Community Grid team, between September 24 and September 30. You can learn more about how the THOR Challenge is structured in this post by Thomas H.V. Dupont, Captain of the CRUNCHERS SANS FRONTIERES team.

Last year, 58 teams with 16,000 volunteers from 19 countries donated 1,172 hours of computing time during the THOR Challenge (second edition). Can we beat last year's statistics? If you are a team captain, register your team today. And if you're a team member, tell your captain that you'd like the team to be part of a challenge that aims to donate a record amount of computing time to seven worthy projects.

Thank you to everyone who supports the THOR Challenge, and who donates their computing power to World Community Grid.

@Norton ? Starts in a WEEK!

News Article HERE. Although this is all of it