WCGrid News and Talking Points!!

[Arjai]

February 2023 OpenZika Project Update​

The OpenZika team has published a new research paper outlining the progress they have made after their partnership with WCG

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Project: OpenZika

Published on: 9 Feb 2023

Brief history of the OpenZika project

Dr. Carolina Horta Andrade (Faculdade de Farmácia Universidade Federal de Goiás, LabMo), together with Dr. Sean Ekins (Collaborations Pharmaceuticals, Inc.) and Dr. Alexander Perryman (Rutgers University–New Jersey Medical School) started the OpenZika project in May of 2016 in collaboration with IBM WCG to identify possible inhibitors of the Zika virus.

By November, the list of 7,600 potential compounds was screened to test their efficacy against the NS3 helicase, a Zika virus protein that allows it to unwind its duplex RNA. The list of molecules was reduced to eight compounds, five of which were subsequently verified to be safe by a study conducted at the University of California, San Diego. In March of 2017, the team was ready to move onto the second stage of the project. The team used a server to create a large library of 30.2 million compounds to be tested against the NS2B-NS3 protease, NS3 helicase, and NS5-polymerase proteins. Running computational screening on this large library was only possible thanks to the combined efforts of the World Community Grid (WCG) volunteers.

Powered by a community of 80,000 volunteers who donated nearly 73 CPU years a day on average to the WCG project, the OpenZika team was able to finalize their modeling and the project was completed in December 2019. The next phase was focused on the experimental validation and prioritization of the selected molecules.

Figure 1: Total CPU years donated to the OpenZika project had been steadily increasing since May 2016 till December 2019.

New developments

In October 2022, the team’s four years of research culminated with a publication in the Journal of Chemical Information and Modeling[1].

The paper highlights the computational process and the validation steps performed during and after WCG analysis. The research team published the results for three important Zika virus proteins: NS3hel, NS2B-NS3pro, and NS5 RdRp. Using WCG, the researchers searched millions of commercially available compounds and identified 61 possible compounds of interest for further screening and optimization.

After the massive docking calculations, the compounds were filtered using machine learning models developed by the LabMol group to identify those that were cytoprotective against Zika Virus infection. Then, compounds that were predicted to pass the blood brain barrier were retained, in order to select those that could counteract the effects the virus has on the central nervous system. Finally, a medicinal chemistry inspection identified and selected compounds with desirable features present in existing drugs.

Figure 2: Description of the discovery pipeline; created by Bruna K. P. Sousa from Dr. C. Horta Andrade lab

From almost 404 million results generated by WCG, amounting to almost 93 thousand years of computation, 61 hits were prioritized for testing. Using enzymatic and phenotypic assays, five compounds were ultimately selected as they inhibited the function of or destabilized the three viral proteins of interest, NS2B-NS3 protease, NS3 helicase and NS5-polymerase proteins. Further tests identified 8 compounds as being able to protect the cells from death caused by the virus, while showing low cellular toxicity in liver and kidney-derived cells. The two sets of 5 and 8 molecules overlap for two compounds, named by the authors LabMol-301 and LabMol-212.

Dr. Carolina Horta Andrade: “This work has demonstrated the importance of the integration of computational and experimental approaches, as well as the potential of large-scale collaborative networks to advance drug discovery projects for neglected diseases and emerging viruses, despite the lack of available direct antiviral activity and cytoprotective effect data, that reflects on the assertiveness of the computational predictions.”

The results of this research are exciting, and further optimization could lead to these molecules being tested as antiviral treatments for Zika virus. The researchers are now looking for partners for performing the hit-to-lead optimization with chemical synthesis and further experimental validations.

We thank the volunteers who made these findings possible, and to the OpenZika team for sharing this exciting update and their continued involvement with WCG. If you have any comments or questions, please leave them in this thread for us to answer. Thank you for your support.

Entire Post, HERE

I want to apologize for not doing updates for the last 2 years. I want to continue this but, my spare time has been minimal, at best. I hope to update this more, moving forward. Although, I know I will not be able to get every post, I will try to do one a month, at least. Due to my work schedule, that is about all I can promise, but hope to do more.

 

[phill]

You're doing all you can @Arjai , I think people will appreciate that more than anything!! Keep up whatever you can, we can always try and get someone else on standby to help out if anyone has a bit of time to help out

 

[Arjai]

Hardware Recovery Update​

The website has been restarted and we are working on rebuilding the science database so BOINC can restart soon.

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Published on: 14 Mar 2023

Brief history

On March 1st, we suffered a disk failure that prevented communication between our science and BOINC filesystems, and brought down the website and forum as well. Initially, it looked like a RAID controller failure. What should have been a routine fix turned into a lengthier endeavor when we realized the issue was much more severe. It turns out the PCI bus failed, meaning we needed to move all of our disks to an alternate storage system, and rebuild the RAID configuration. Fortunately, Sharcnet was able to locate an identical, older storage system that we could use during the recovery.

The data center was able to put all of our disks into a spare system and the rebuilding process began. While the data integrity was confirmed, we could not boot the system; we needed to fix the system disks to work in the new server.

Website restart

On March 13, finally, we managed to restart the website/forum databases. Initial performance and overall availability/functionality remains limited due to continued storage recovery efforts and backup. While the stats cannot be updated until we fully restart BOINC and download already processed WUs - no work will be lost, and all credit will be given, as we will extend the time for returning results.

We are immensely grateful for the positivity that we received during the process.

We have ARP, SCC, MCM updates in the pipeline - just waiting for the full recovery from our storage failure.

If you have any comments or questions, please leave them in this thread for us to answer. Thank you for your support, patience and understanding.

WCG team

 

[Arjai]

Research update from the ARP team (March 2023)​

A short update from the ARP team, including details about the changes they are making to their storage system.

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Project: Africa Rainfall Project

Published on: 15 Mar 2023

Background

The Africa Rainfall Project aims to run computer simulations of rainstorms in sub-Saharan Africa to improve weather forecasts for the region. Providing accurate weather prediction data to the local farming community is crucial for agriculture and self-sufficiency. Comparing results obtained through computing rainfall data from various sources using the World Community Grid, scientists can create increasingly accurate forecasts and improve future simulations and in turn weather predictions. To learn more about the specific details of the project, check out our ARP update from March 2022.

As of December 2022, the ARP team has paused releasing new work units, until they resolve the capacity limitations of their storage system. More about this pause can be read in our work unit status forum update.

The last 100 days for the African Rainfall Project

We asked the ARP team about their recent developments and this is what they shared with us:

“It has been really quiet for the African Rainfall Project, at least on the front end. Behind the scenes, necessary changes now have been made to start going again. In previous news items, we talked a lot about the data volumes involved, which are indeed impressive. It is, however, also a major problem in terms of storage and moving them from one place to another. In the case of ARP, the results from the volunteers are sent by the WCG to computers at SURF, the collaborative organization for IT in Dutch education and research. The first 200TB could be stored on disk, which is relatively easy to access. That was, however, also the maximum amount allowed. There is also “work storage”, where results can be analyzed and compared. Officially, the maximum amount allowed there is 50TB but ARP had sent 150TB, so the data needed to be moved elsewhere. In this case, “elsewhere” was tape storage, which is actually still the cheapest way to store data but also involves physically moving tape-reels to and from reading and writing units. Even though these tapes are moved by a robot, one can imagine that it takes some time and one would only move data on or off tape once every now and then. One could probably give the command to simply copy every file drive to tape but that would probably get stuck somewhere and one may also have transcription errors. Instead, we moved the data one generation at a time (i.e., two days of simulation)and used a so-called hash function to make sure the bits on the original medium were the same as on the new medium.

Read more about the African Rainfall Project, aka the rest of this post, HERE.

Heavy rain in Africa. Photo: Jan Friesen

​

 

[Arjai]

Research update from the MCM team (March 2023)​

The MCM team’s research into lung cancer biomarkers has identified 26 genes that are present with top scores across all the signature sizes considered. This update focuses on VAMP1, a gene linked to patient survival and differentially expressed in normal lung compared to lung cancer.

Project: Mapping Cancer Markers

Published on: 20 Mar 2023

*This is a large update so, I will provide a link at the end of this truncated post.*

Terminology

• Gene signature: A set of genes shown to have a specific role in a disease is called gene signature. When such a signature can predict the presence of a disease, it is called a diagnostic gene signature. When signature relates to survival, it is called prognostic signature.
• Matthews correlation coefficient: A statistical method used to evaluate the performance of a predictive model. It measures the differences between actual values and the predicted ones.
• Probes: Short DNA sequences targeting a small region of a transcript (gene). To make them more specific, probes are organized into probe sets, which are used to detect and quantify the presence of gene sequences through hybridisation due to complementarity between the probe and the target.

Background

The Mapping Cancer Markers project aims to identify the markers associated with various types of cancer using a heuristic search algorithm. The project analyzes millions of data points collected from patient tissue datasets and identifies patterns that can detect cancer earlier, identify high-risk patients and customize treatment for individual patients. Initially focusing on lung cancer, the project expanded to investigating ovarian cancer, and most recently analyzing sarcoma.

By November 2021, WCG volunteers donated over 800 million workunits for research into multiple types of cancer, with 193, 379 and 245 million work units crunched for lung, ovarian and sarcoma cancers respectively. To date, over 810,000 years of computational research has been donated to MCM, with close to 240 years generated every day. Thank you for helping us uncover insights into cancer signatures. *!!*

Figure 1: Number of completed work units per cancer type and signature size.​

...

WCG volunteers tested 9 trillion (9×1012) candidate lung cancer signatures divided into several different diagnostic signature sizes. We then considered the signatures with Matthews correlation coefficient in the 99.999 percentile among all signatures of that same size. Figure 2 shows the distribution of biomarkers in the signatures. Count is the number of times a probe is present in the top signatures for its size.

Figure 2: Frequency of each count (i.e., number of times a probe is present) per signature size.
​

...
When considering the probesets in the 99th count percentile and present in at least 20 signature sizes, we can see that there is higher overlap in the signatures of sizes from 10 to 23, providing an indication that the best signature size window is in this range (Figure 3). This is going to be important for future studies on diagnostic signatures. Our aim is to release all data calculated with the help of WCG volunteers in a freely accessible database, where other researchers will be able to compare their results to the “lung molecular landscape” we obtained.

Figure 3: Heatmap of the 143 probes present in more than 20 signature sizes, and the sizes where they are present.​

Exploring the results further, we found that 28 probesets (mapped to 26 genes), are present in all signature sizes. One of these genes, VAMP1,
is particularly promising as its protein is involved in synaptic vesicles fusion to the presynaptic membrane. Below are the cellular localizations for VAMP1 as per UniProt,
and its 3D structure predicted by AlphaFold.

GO ID​	Qualified GO term​
GO:0005739	mitochondrion
GO:0005741	located_in mitochondrial outer membrane
GO:0005829	located_in cytosol
GO:0005886	is_active_in plasma membrane
GO:0005887	plasma membrane

Figure 4: Cellular component annotations and protein structure for VAMP1 (as predicted by AlphaFold).​

When investigating VAMP1 in external datasets to validate its importance, we found that it is significantly linked to the smoking status in lung cancer patients (through thecBioPortal[/COLOR]). From our earlier study, we considered smoking-specific microRNAs that may regulate VAMP1 (as determined by our mirDIP data portal). Interestingly, hsa-miR-1262, a microRNA specific for former smokers, regulates VAMP1. None of the microRNAs specific to current smokers or never smokers appear to be relevant. Importantly, VAMP1 is protective for overall survival in lung cancer (high expression results in longer survival), making it a potential prognostic marker.

Figure 5. Kaplan-Meier plot shows that individuals with high expression of VAMP1 (in red) survive significantly longer compared to individuals with low expression of VAMP1 (in black). This shows that VAMP1 is a prognostic marker.

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The protective value of VAMP1 is further supported by the gene expression in the two main lung cancer histologies, as shown in Figure 6. Normal samples express a much higher level of VAMP1 compared to cancer samples. This highlights that VAMP1 is also a potential diagnostic marker.

Figure 6. Expression of VAMP1 in normal and lung cancer samples.

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Extending our observation beyond lung cancer, as described in our initial WCG project description, we find that VAMP1 behaves in a similar way in the majority of tested cancer as shown in Figure 7. This suggests that VAMP1 is a key player in carcinogenesis, and may be involved in a mechanism linked to the hallmarks of cancer.

Figure 7. VAMP1 expression in normal and cancer for 22 different cancer types or subtypes. (Significant differences by Mann-Whitney U test are marked with red font).

​

We are excited about these results and will share more in the future as we continue with the validation of our results from lung cancer analyses.

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If you have any comments or questions, please leave them in this thread for us to answer. Thank you for your support.

WCG Team

All links are linked.
The full update is : HERE

 

[Arjai]

SCC Project starts a new phase in their quest for curing childhood cancers​

The SCC project has entered the next phase of the research and new workunits have been prepared for the BOINC restart.

Project: Smash Childhood Cancer

Published on: 22 Mar 2023

Background

While the proteins and other molecules that play key roles in childhood cancers have been identified, finding chemical compound (drug) candidates that can target these molecules and modify their function is a lengthy process. Using the computing power of WCG, the Smash Childhood Cancer team has been able to search millions of drug candidates for possible clinical application.

The project has been running intermittently, identifying possible drug candidates and then testing them in the lab. As of December 2020, 48,000 hours of calculations have been donated to the SCC team by WCG volunteers. Since then, the team has been busy validating the results they received (see recent updates).

March 2023 update

We are excited to share an update from the Smash Childhood Cancer team about the start of the new phase in their quest for curing cancer. The new target protein is MyoD1 (Myogenic Differentiation 1 protein) and one of its mutations, L122R. MyoD1 is a transcription factor that activates muscle-specific genes, and is involved in the switch between cell growth and cell differentiation. The loss of control over this switch can cause the formation of rhabdomyosarcomas1.

L122R is a mutation frequently found in rhabdomyosarcoma, and it is linked to a worse prognosis. Considering the crystal structure deposited in Protein Data Bank, the goal is to find compounds that act on the mutant-type but not on the wild-type.

Crystal structure of MyoD bHLH domain-DNA complex: perspectives on DNA recognition and implications for transcriptional activation3.
​

New SCC work units have been prepared to help with the search, and volunteers who follow this project will be able to download them once we restart BOINC after the storage failure.

If you have any comments or questions, please leave them in this thread for us to answer. Thank you for your support, patience and understanding.

WCG team

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Sources:

1. Sebire NJ, Malone M. Myogenin and MyoD1 expression in paediatric rhabdomyosarcomas. Journal of Clinical Pathology 2003;56:412-416.
2. A MYOD1 Mutation Cooperates with PI3K Pathway Activation in ERMS. Cancer Discov 1 July 2014; 4 (7): OF19. https://doi.org/10.1158/2159-8290.CD-RW2014-109.
3. Crystal structure of MyoD bHLH domain-DNA complex: perspectives on DNA recognition and implications for transcriptional activation. Ma, P.C., Rould, M.A., Weintraub, H., Pabo, C.O. Cell 77: 451-459. PubMed: 8181063. PDB DOI: https://doi.org/10.1016/0092-8674(94)90159-7

 

[Arjai]

New team member and research projects at SCC​

The SCC team shared news about the next phase of their research and introduced a new team member who will help with computational modeling for developing new cancer-treating drugs.

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Project: Smash Childhood Cancer

Published on: 6 Apr 2023

Background

New team member!

We’re excited to welcome Nikita Rozanov as the newest member of the SCC research team.

As a recent graduate from Oregon State University with a Bachelor of Science in Chemical Engineering, he worked as a software engineer at Intel and Amazon. His interest eventually migrated towards molecular research using computer-modeled simulations and began working as a visiting researcher at Johns Hopkins University. There, he developed molecular dynamics simulations to predict how nanoparticles interact with proteins.

For the WCG SCC project, Nikita’s expertise in creating computer simulations of proteins and molecules will help in the search for new cancer-treating drugs.

FLI1 research

The SCC team has selected a new target protein – FLI1 – a member of the ETS transcription factor family that controls cell proliferation, differentiation and survival. Fusion of FL1 gene and EWSR1 is frequently present in cases of Ewing Sarcoma and other cancers1. EWSR1 encodes for an RNA-binding protein (EWS), and when EWS is fused to FLI1 the latter becomes constantly activated (instead of finely regulated) creating the molecular environment for tumor formation. The EWS-FLI1 fusion protein has been thought to inhibit p53 and/or activate NOTCH signaling, accelerating sarcoma progression. Useful FLI1 inhibitors need to specifically target this fusion protein but not other related ones to avoid inadvertent side effects2.

If you have any comments or questions, please leave them in this thread for us to answer. Thank you for your support, patience and understanding.

WCG team

SCC work units for FLI-1 and MyoD1 targets​

The new SCC work units focus on new drug targets for EWS-FLI-1.

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Project: Smash Childhood Cancer

Published on: 21 Apr 2023

All the Info in this UPDATE

 

[Arjai]

The Dylan Bucci Grid Computing Club at Sisler Cyber Academy​

Sisler High School’s Cyber Academy (Winnipeg, MB) has expanded their partnership with World Community Grid by starting a computing club to honor one of their late classmates. They have spread WCG awareness to their local community as they believe learning about grid computing at school has many positive effects.

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Published on: 17 Apr 2023

Sisler High School’s Cyber Academy in Winnipeg, MB, Canada has been collaborating with WCG for many years, not only by donating substantial computing capacity but by engaging students with an understanding of high-performance computing and the science it enables. WCG is immensely grateful for their commitment to supporting world-changing research and sharing the platform with their local community. We recently interviewed Sisler Cyber Academy Instructor Robert Esposito and Grade 12 student Eric Easter to discuss how they integrated citizen science into their curriculum and student culture.

Sisler’s involvement with WCG started in 2015 with a grade 9 project requiring students to set up WCG on several computers. In 2018, Dylan Bucci, a 10th grade student at Sisler Cyber Academy, decided to get involved with WCG. In addition to wanting to support the goals of WCG in helping with early diagnosis of cancer, Dylan had a personal motivation since many of his family and friends had passed away from this disease. He spent many hours of his free time reconfiguring a dozen donated servers, and within a year, he contributed 168 years of processing time to World Community Grid’s cancer research (CTV news Winnipeg). He shared his enthusiasm and interest in the WCG with other students, and the volunteer base started to grow rapidly. In 2019, Dylan along with Mr. Esposito became the first volunteers to meet Dr. Jurisica and the MCM team at Krembil Research Institute in Toronto.

Dylan Bucci, Sisler Cyber Academy instructor Robert Esposito, and Dr. Igor Jurisica during their tour of Krembil Research Institute
​

Sadly, in August 2020 Dylan was diagnosed with Stage 4 Ewing’s sarcoma, a rare type of cancer that occurs in bones or the soft tissue around them. Cancer had rapidly metastasized to his hips, spine, pelvis, ribs, lungs, and further up his arm. Despite treatments and his relentless fight, Dylan passed away on February 19, 2022, at the age of nineteen. Although Dylan was not able to achieve all his dreams and potential, he has inspired many students to continue his mission.

To carry on Dylan’s legacy, Mr. Esposito started the Dylan Bucci Grid Computing Club, which teaches new students about the WCG, how to use the BOINC platform to support scientific discoveries, and discusses new developments in research initiatives. They have a notable number of student members, including Eric Easter who acts as the club’s Student Lead and helps manage the club’s equipment. Involvement with WCG projects is so high, students have expressed interest in another trip to Krembil, following in Dylan’s footsteps. Mr. Esposito said he would be thrilled to take new students on that trip so they can learn more and be inspired by meeting the scientists who directly benefit from their support of the WCG.

​

Mr. Esposito believes that grid computing can be more than just an extracurricular activity for students to learn about. WCG can also be directly integrated into any technology curriculum. For example, teachers could utilize WCG as an all-encompassing class technology project. A class WCG project would involve learning about computer hardware, software, networking, and cyber security. He also believes it’s an ideal cross-curricular project which incorporates both science and technology. Eric, who used WCG at school for competitions and recreational use, said he learned valuable technical knowledge while contributing to a good cause.

Eric decided to build a custom grid machine that utilizes a combination of central and graphical processing power. There was a lot of trial and error during the design and build process. Eric spent a grueling number of hours researching and testing various settings to achieve optimal stability at peak computational power.

Eric hopes to encourage more schools to introduce grid computing into their curriculum, for the benefits it would provide to global research efforts, and to students seeking to contribute to research on health and sustainability with their computer, Android, or Raspberry Pi devices.

​

We would like to thank Mr. Esposito and Eric for providing the material and images used in this article. If you would like to help them, they accept donations for new computers and graphics cards through the Children's Heritage Fund in memory of Dylan Bucci. You can also contact them through their website.

We aim to provide an exciting platform for motivating the new generation. If you are a teacher or a student who is interested, or if you know those that might be, please contact us directly.

WCG team

More Info in WCG post, HERE.

 

[Arjai]

WCG Club at Boca Raton Community High School​

Students at Boca Raton Community High School have been contributing to the World Community Grid since 2020, and the partnership is expanding with the creation of the new WCG Club.

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Published on: 24 Apr 2023

Boca Raton Community High School is on a mission to expand science curriculum for its students, and introduce them to high-performance computing on the grid and its benefits to research across many domains of science. We talked with a teacher and Science Olympiad coach from Boca Raton Community High School, Jonathan Benskin, about how he expands biology classes with World Community Grid research and how he strives to bring supercomputing into the high school.

Late in the 2020 academic year, Mr. Benskin introduced a class of juniors to the World Community Grid, which they found greatly interesting. Shortly after, students created a WCG Club at the high school with the aim to grow the base of volunteers, just in time for new students to learn about the platform during the next academic year.

Students presented completed WCG projects in groups of two and current projects in groups of four. These presentations focused on the scientific goals of each project and even ventured into the computational strategies employed by each to complete work units. As part of their preparations, the team (through Mr. Benskin) asked WCG project team leads questions, and ran their ideas by them. Mr. Benskin believes this assignment deepened students’ appreciation for the WCG research and helped them understand the impact that their donated computing power makes to advance science.

​

Fundraising in their local neighborhood was another major component of the campaign. Students were given a choice for roles within the club, with the first group working to raise funds through persuasive presentations. They have been successful in obtaining funding from a local business and are always searching for new businesses to help them. The second group was tasked with determining what equipment to buy with their funds, carefully balancing performance and cost. So far, they have fundraised enough to build three new high-end workstations, enabling them to substantially increase their contribution to WCG. Their campaign is far from over, though, as they plan to become the largest high school contributing partner.

Students working on optimizing cost-performance of the new computing hardware.
​

The students of Boca Raton High School aspire to become one of the main contributing partners on the WCG. Their initial success is a great motivating factor for them as they are always looking for new ways to support a project that means a lot to them. We are extremely grateful for their contribution and applaud their enthusiasm.

For any questions, please comment on our Boca Raton H.S. Announcement forum thread.

WCG Team

More of the Story, HERE

 

[Arjai]

Research update from the MCM team (April 2023)​

The MCM team’s research into lung cancer biomarkers has identified 26 genes that are present with top scores across all the signature sizes considered. This update focuses on a potential biomarker gene called FARP1, which is linked to lung cancer metastasis.

Project: Mapping Cancer Markers

Published on: 28 Apr 2023

Background

The Mapping Cancer Markers project aims to identify the markers associated with various types of cancer with the goal to identify biomarkers to detect cancer earlier, identify high-risk patients and customize treatment for individual patients. To date, over 818,200 CPU years have been donated to the project by WCG volunteers across the world. Thank you all for your support.

In our previous MCM project update, we started to introduce putative lung cancer biomarkers that are present with top scores across all the signature sizes considered. The first update focused on VAMP1, a gene linked to patient survival and differentially expressed in normal lung compared to lung cancer. This update highlights a potential biomarker gene called FARP1, which is linked to metastatic development.

New developments

The protein FARP1 encodes is a guanine nucleotide exchange factor that plays a role in dendritic formation and growth. FARP1 can be found in cell membranes, cytoplasm, synapses and dendrites (Uniprot). Since both VAMP1 and FARP1 are involved with synapses, we investigated whether the two proteins interact together. While they do not interact directly (IID; Integrated Interaction Database) they share two interacting partners, RAB6A and APBA1. RAB6A plays a role in neuron projection development, while APBA1 regulates APP (Alzheimer's disease amyloid precursor protein), and is thought to have a role in the secretion of synaptic vesicles.

Neither RAB6A nor APBA1 are present in the top 99th percentile, but they suggest that there is indeed a neuronal signal associated with our two proteins of interest – VAMP1 and FARP1. The importance of this finding is related to the difficult-to-study connection between lung cancer and one of its most frequent sites of metastasis: the brain[1].

We thus decided to investigate further the importance of this gene using external datasets. FARP1 is a potential diagnostic biomarker, similar to VAMP1, as highlighted in Figure 1. Furthermore, FARP1 is differentially expressed in metastatic samples, strengthening the connection between the molecular function of this protein and the phenotype it can help develop.

Figure 1. Expression of FARP1 in normal samples, lung cancer and metastatic samples.
​

While we keep validating our results, we are excited about the impact our results can have on patient lives and research, computed by thousands of volunteers. Thank you for the contribution to this research.

If you have any comments or questions, please leave them in this thread for us to answer. Thank you for your support, patience and understanding.

WCG team

A little more info, HERE

 

[Arjai]

Research update from the Microbiome Immunity Project team (May 2023)​

The Microbiome Immunity Project team has published a new article about the structure and function of human microbiome proteins.

Project: Microbiome Immunity Project

Published on: 5 May 2023

Background

While bacteria in general can be harmful to humans, as it can cause diseases such as pneumonia, meningitis, strep throat, food poisoning (Escherichia coli and Salmonella), bacteria in the human gut also have protective functions. For many years scientists have studied the various types of bacteria in the human body and characterized those that could be harmful or useful, but the vast majority remain poorly characterized. With an estimated 3 million unique bacterial genes known to exist, studying all of the resulting proteins and determining their function is a complex task.

The Microbiome Immunity Project started in August 2017 with the goal to speedup protein molecule research thanks to the power of grid computing. By the time the computation finished in December 2021, World Community Grid volunteers donated nearly 146,000 CPU years to the MIP. This effort enabled the team to predict the structure of almost 200,000 proteins, discover over 150 new protein shapes (folds), describe several previously unknown functions of protein structures, and nearly double the number of annotated proteins in the human gut microbiome.

Protein Universe Paper

The MIP team has recently published their paper in Nature Communications titled Sequence-structure-function relationships in the microbial protein universe[1]. This article explores the notion that proteins with similar sequences will not necessarily create similar structures that perform the same functions, contrary to a long-held belief among scientists. Using the MIP database that WCG volunteers helped create, the paper explores examples where proteins similar in sequence perform different functions.

The MIP team analyzed 2 million protein sequences that had no known structure in any other database. They then used Rosetta and DMPFold methods to predict the protein structures in a three-step process. To filter out low quality predictions, they first determined a threshold amount of coil residues (that form helices) above which the structures were not reliable. Second, they used confidence and quality assessment scores to determine the predicted quality[2]. Third, priority was given to models in agreement between the 2 methods. In the end, about 200,000 models were identified and characterized.

This study paves the road to the development of tools to explore and predict site-specific protein functions for other organisms as well, in order to better understand the role of specific structures and functions related to biological functions.

“Until now, we have been talking about the microbiome in the same language one would use to describe the biodiversity of a rainforest,” Dr. Tomasz Kosciolek, a member of the MIP research team says. “We hope to start talking about it in more mechanistic terms, like what molecules might amplify, inhibit or change certain biological processes.”

Thank you to the Microbiome Immunity Project team for providing this update. If you have any comments or questions, please leave them in this thread for us to answer. Thank you for your continued support that accelerates large-scale scientific research for the betterment of humanity.

WCG team

A bunch more Info, I left out, HERE.

 

[Arjai]

World Community Grid: Upcoming System Outage July 25th On July 25th, all systems will be down, including our website/forums and BOINC. 6/23/2023 9:59:21 PM · more...

?

 

[phill]

World Community Grid: Upcoming System Outage July 25th On July 25th, all systems will be down, including our website/forums and BOINC. 6/23/2023 9:59:21 PM · more...

?

Wonder how long that will last.....

 

[bubbleawsome]

Wonder how long that will last.....

 

[NastyHabits]

I just noticed it was JULY 25th, not today. Sometimes I wonder about myself.

 

[phill]

I just noticed it was JULY 25th, not today. Sometimes I wonder about myself.

I thought it was June so shows sometimes what I'm doing

 

[Arjai]

MCM team has been researching GSDMB​

We continue our work on characterizing lung cancer biomarkers identified in the MCM1 project. This update focuses on GSDMB, a gene associated with lung cancer survival and differentially expressed across multiple cancer types compared to normal tissues.

Project: Mapping Cancer Markers

Published on: 12 Jul 2023

Background

Recognizing patterns in cancer patients can have many benefits, such as making it possible to detect signs of cancer in other patients and personalizing each patient’s treatment to fit their specific cancer profile. Since November 2013, World Community Grid volunteers have donated over 820,800 CPU years to the project, helping analyze research data on cancers and sarcomas at a speed never thought possible before. We are immensely grateful for the volunteers who continue to donate to this project, and help us accelerate the search for better biomarkers.

We continue our analysis of the most common biomarkers amongst lung cancer patients. Following discussion of the genes VAMP1 and FARP1 that were described in our March and April updates, here we focus on GSDMB.

GSDMB Research

Gasdermin B (GSDMB) is a protein in the GSDM family, which share similar structures and typically play roles in cell proliferation and differentiation[1]. The GSDM family are known for their role in triggering pyroptosis, a highly inflammatory type of cell death, which they accomplish by forming pores in cell membranes[1]. GSDMB has also been identified to regulate epithelial cell growth independently of its role in pyroptosis (Uniprot). GSDMB is considered unique among the other members of its family, and its role in various types of diseases and cancers is relatively under-studied. It has been shown that genetic variants in GSDMB are linked to increased susceptibility to diseases like asthma and inflammatory bowel disease (IBD)[2].

Similarly to VAMP1 and FARP1 genes, we investigated the role of GSDMB in lung cancer, and found that its presence has a protective role in lung cancer, as shown in Figure 1 (data from KMplotter).

Figure 1. Survival curves for patients with high and low expression of GSDMB.
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Extending our observation beyond lung cancer, as it is an aim of our WCG project, we find that GSDMB behaves in a similar way in the majority of tested cancers, as visible in Figure 2. This suggests that GSDMB has an important role in carcinogenesis, and may play a role in hallmarks of cancer. This has been confirmed in the literature, where an association has been found between GSDMB expression levels and cancers such as gastric cancer, breast cancer[3], and bladder cancer[4].

Figure 2. Expression of GSDMB in normal and cancer tissues for multiple cancer types.
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Using Human Protein Atlas (HPA), we also identified strong prognostic value of GSDMB protein, as shown in Figure 3.

Figure 3. Prognostic value of GSDMB protein in renal (unfavourable), urothelial and cervical cancers (favourable).
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Exploring GSDMB expression using the GTEx portal (GTEx), we identify which cells in the lung express it, as shown in Figure 4.

Figure 4. Single cell data from the GTEx portal show strong expression both in epithelial and immune cells.
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If you have any comments or questions, please leave them in this thread for us to answer. Thank you for your continued support.

WCG team

ok, SO, I am not going to claim a total understanding of this. GSDMB proteins are both good AND bad? I may need to re-read this when my brain is less foggy. Anywho, another milestone in Cancer research!! WCG, despite the recent teething pains, is STILL the BEST thing I do everyday! It is the ONLY reason I currently own 12 computers(only 3 running now, due to heat). I should have 9 running this winter and the other 3 are for contests, they're a bit power hungry.

I hope everyone is well and not too worn out by the grind, like me. LOL


Oh, the link HERE, also has a bunch of footnotes and References

 

[Arjai]

ARP storage update​

The ARP team is in the process of moving their data from SURF, a collaborative organization for IT in Dutch education and research, to a cloud service.

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Project: Africa Rainfall Project

Published on: 19 Jul 2023

Background

The Africa Rainfall Project (ARP) aims to simulate rainstorms in sub-Saharan Africa to improve regional weather forecasts. Providing accurate weather predictions is crucial for self-sufficiency of the local farming community. By comparing results obtained through computing rainfall data from various sources using the World Community Grid, scientists can create increasingly more accurate forecasts, improve future simulations and in turn weather predictions. To learn more about the specifics of this project, read our March 2022 research update.

Due to capacity limitations of their storage system, the release of new work units has been paused since December 2022. To read more about the details of this storage limitation, please refer to ARP update from March 2023.

New home for Africa Rainfall Project data

We asked the ARP team for an update on their storage limitation, and this is what they shared with us:

“The ARP project running at the WCG produces a very large dataset. At this moment, there is about 300TB in more than four million files. Storing and moving such enormous amounts of data is not trivial. Until now, all data was stored in the computing centre of SURF, the cooperative association of Dutch educational and research institutions. After about four years of support, the ARP at SURF is about to end. So what to do with the data?

We were very fortunate that, earlier this year, a cloud service provider has agreed to host the data. Presently, the file formats are not very user-friendly but once the move is complete, the files will be transformed to a format that can be used by most researchers. First, this will be organized in individual files that the user has to download. Pretty soon, however, we hope to have a simple map-based interface that would enable users to outline an area of interest and select a period of time as well as the weather variable of interest, after which all chosen data can be downloaded in one file. Stay tuned!”

Thank you to the ARP team for their continued partnership with WCG and for their help in preparing this update. If you have any comments or questions, please leave them in this thread for us to answer.

Thank you for your support!

WCG team

 

[Arjai]

I should have some updates on Wednesday, this week. I have too much work to do between then and now. So, if I have the energy, I will post them up then.

Hasta Luego!

 

[phill]

I should have some updates on Wednesday, this week. I have too much work to do between then and now. So, if I have the energy, I will post them up then.

Hasta Luego!

Do as and when you can sir!! I know how busy these updates can keep you!!