Cancer Complexity Knowledge Portal Launched

The Cancer Complexity Knowledge Portal has officially launched. Funded by the National Cancer Institute Division of Cancer Biology, the portal enables researchers to submit multi-faceted queries related to the latest discoveries, data, tools, methods, and publications from three cancer research communities:

  • Cancer Systems Biology Consortium (CSBC), which aims to address the challenges of complexity in cancer research through a combination of experimental biology and computational modeling, multi-dimensional data analysis and systems engineering.
  • Physical Sciences in Oncology Network (PS-ON), which supports research programs that connect cancer biologists and oncologists with scientists from the fields of physics, mathematics, chemistry, and engineering to address some of the major questions and barriers in cancer research.
  • Cancer Tissue Engineering Collaborative (TEC), which supports the development and characterization of biomimetic tissue-engineered technologies.

Sage Bionetworks serves as the resource coordinating center for CSBC and PS-ON and developed and maintains the portal.

Sample queries:

Explore the Cancer Complexity Knowledge Portal

Sage Joins DAPI Project for Down Syndrome Research

NIH Award Funds Data Coordinating Center for Down Syndrome Research

The new initiative will fuel collaboration and discovery about the biology of Down syndrome and its co-occurring medical conditions

PARTNER PRESS RELEASE:

DENVER, Nov. 5, 2020 /PRNewswire/ — University of Colorado Anschutz Medical Campus announces scientists and data experts are joining forces to create the world’s first centralized platform for Down syndrome researchers to share, access, and analyze data. The goal of the new initiative, called the “Data Management and Portal for INCLUDE (DAPI) Project,” is to accelerate discoveries and advance medical care for individuals with Down syndrome. The National Institutes of Health (NIH) recently awarded a grant totaling $19.5M over five years to develop the center as part of the INCLUDE Project (INvestigation of Co-occurring conditions across the Lifespan to Understand Down syndromE).

The DAPI Project is co-led by Dr. Adam Resnick, Director of the Center for Data Driven Discovery for Biomedicine (D3b) at Children’s Hospital of Philadelphia, Dr. Joaquin Espinosa, Executive Director of the Linda Crnic Institute for Down Syndrome at the University of Colorado Anschutz Medical Campus, and Dr. Justin Guinney, Vice President of Computational Oncology at Sage Bionetworks. DAPI Project leaders will work closely with NIH INCLUDE Project staff to develop the center. This collaboration brings together strong expertise in Down syndrome research and open, data-driven science.

READ FULL PRESS RELEASE

Discovering Keys That Could Unlock Better Personalized Treatments to Destroy Cancer

International neoantigen initiative Tumor Neoantigen Selection Alliance (TESLA) identifies parameters for cancer vaccine or cell therapy advancement

 

SAN FRANCISCO – Neoantigens, tiny markers that arise from cancer mutations, flag cells as cancerous and could be the key to unlocking a new generation of immunotherapies. Targeting the “right” neoantigens – in a cancer vaccine or a cell therapy – has the promise to eliminate a patient’s cancer with minimal side effects. But hundreds of mutations can exist in a tumor, and only some can give rise to neoantigens that can trigger an immune response against cancer. The question is, which ones?

Scientists from an initiative launched by the Parker Institute for Cancer Immunotherapy (PICI) and the Cancer Research Institute called the Tumor Neoantigen Selection Alliance (TESLA) have discovered parameters to better predict which neoantigens can stimulate a cancer-killing effect. TESLA brings together a constellation of 36 top biotech, pharma, university and scientific nonprofit research teams. Their findings were published online today in Cell and could spawn a new generation of more effective, personalized cancer immunotherapies. Read full release…


Kristen Dang and Justin Guinney led the Sage Bionetworks team that collaborated on this study and paper.

AACR Project GENIE Serves As Hub and Harmonizer for Cancer Data

New data release highlights Sage’s key role in mapping data and enabling broader accessibility

 

FEATURED PROJECT

AACR Project GENIE (Genomics Evidence Neoplasia Information Exchange) launched in 2015 to serve as a registry for pan-cancer data from tens of thousands of patients treated at the eight participating institutions. The registry enables the mapping of cancer genomic data to clinical outcomes. Having patient data from AACR Project GENIE helps to improve clinical decision-making, especially for rare cancers and rare variants in common cancers.

Sage Bionetworks has served as the data hosting and integration hub, overseeing data ingestion and processing, and two data releases per year. Sage has contributed to the development of detailed data dictionaries and formats, and has deployed operating procedures that describe the workflow streams required of each institution as well as data processing pipelines to validate the data across the contributing centers.

Ensuring the cancer data is processed and standardized so researchers can easily access the breadth of information is a massive project. Over the course of 2019, this group has also been collaborating with teams at Memorial Sloan Kettering and the GDC to convert Project GENIE data from 44,756 cancer cases to be compatible with the National Cancer Institute’s Genomic Data Commons (GDC). (Read more about this impactful data release on the AACR blog.)

In an ideal world, there would be a single standard for clinical patient data. But there isn’t, so sharing cancer genomic data from one medical center to another is far from trivial. In this case, Sage’s Kristen Dang and Thomas Yu, and MSKCC’s Stacy Thomas oversaw the mapping of the data. It required programmatic and line-by-line review in order to convert the data for integration with GDC.

Sage values data accessibility and believes in breaking down barriers that can hinder crucial research. Preparing the initial data release for GDC came with challenges, but the process helped teams address some of the pain points, so future releases will be more streamlined.

UPCOMING DATA RELEASE

There will be an AACR Project GENIE data release in January 2020. Visit the data release log to stay current.

The Value of Team Science in Alzheimer’s Disease Research

Related News: Bringing Open Science to Drug Discovery for Alzheimer’s

The Sage Perspective

Silos in research are slowing us down. This isn’t a revelation, but it is a rallying call for many of us who hope to overcome barriers to advancing research, especially for a disease like Alzheimer’s.

In the study of Alzheimer’s, there has been a spectacular failure in the development of therapies. All the drugs that are allegedly disease-modifying have failed in late-stage clinical trials. The thinking around what causes the disease has not moved beyond a few hypotheses that have taken root.

This has occurred because the scientific community has fallen for the streetlight effect: We continue to expend resources to generate new data on hypotheses that have existing promising data because it is viewed as a safe bet. Given the repeated failure of clinical applications of these hypotheses (e.g. the Amyloid hypothesis), we face the stark reality that the true nature of the disease is a quagmire of uncertainty.

Fundamental shift

Yet there are rational strategies that have been successful in other domains such as finance that the community can use to mitigate that uncertainty. Instead of continuing to accrue data on what isn’t working, we ought to systematically explore the boundaries of our collective knowledge about Alzheimer’s Disease and balance the distribution of resources across low-, medium-, and high-risk ideas. This requires a fundamental shift in how we think about doing science, because no individual contributor can perform all of the tasks necessary to expand our collective knowledge in a meaningful manner.

There are so many silos that a lot of data, new ideas, and hypotheses don’t get shared. There also is some level of distrust in the community by researchers who want to guard proprietary information for the sake of a “magic bullet.” But there is no magic bullet. If we don’t collaborate strategically and diversify our research portfolio, we will continue to fail.

We are at a critical stage in Alzheimer’s Disease research where the community and individual researchers must put aside their individual reservations and work together. We have to let go of what’s not working and acknowledge that there are potentially other factors that affect how the disease behaves. It’s imperative that fresh ideas are given adequate space to succeed and to disrupt current structures to facilitate this exchange. We have to hedge our bets.

Radically open

At Sage, I lead a team that works across several programs that are identifying new drug targets to treat Alzheimer’s disease. There are many different academic institutions that are generating high-dimensional molecular data that can be used to try to identify new genes and pathways that could be fresh drug targets. We, in the spirit of open science, help orchestrate the analytic and data coordination efforts associated with that endeavor.

Our goal is to use a data-driven approach to better understand the underlying molecular mechanisms of the disease. It’s not something that any individual group would have the resources to do effectively. So it really requires a community-driven approach. Sage is positioned to conduct the scientific coordination that can help researchers work more effectively to get at these new ideas that might lead to a successful treatment.

Our primary project is AMP-AD (Accelerating Medicine Partnership in Alzheimer’s Disease), which is a public-private partnership supported by the National Institutes on Aging. We serve as a hub for all the data that’s being generated across the project. It’s a radically open model where all the data become open once they have gone through quality control. You don’t have any publication embargoes or restrictions on data use – aside from adhering to governance standards associated with sensitive human data.

We play a role in trying to increase the transparency of all the analyses that become available. We’re also building partnerships with academic investigators to streamline how we reach a consensus about what the data are telling us about the potential causes of this disease. We want to make sure that any conclusions are consistent across different research teams, because the more generalizable a solution is, the more likely it will lead to a successful treatment.

The long view

In addition to this scientific coordination work, my group is also performing original research on Alzheimer’s Disease. In all of our research, we operate under the same open model as all of our collaborators. Practicing this open approach in our own work is important at Sage. By holding ourselves to the same standard that we ask the community to live by, we can understand and work through any pain points. In this way, we hope to lead by example. At Sage, we do have the benefit of a culture and incentive structure that emphasize the long view versus, say, maximizing revenue in the short term. Being able to think on a longer time scale affords us the ability to make decisions that improve science more materially than if we were to focus on solo – and siloed – projects.

Any approach to tackling how science is done needs to be systematic in order to have long-lasting impact. For Alzheimer’s disease, we have an opportunity to improve how therapeutic development happens. Our vision and hope is that any future compounds that may result from open research we support would be achieved faster and more efficiently, and be made available in an affordable and equitable manner.

Being radically open and collaborative isn’t easy, but operating in a silo won’t get us far enough. We have to be more intentional about team science. Lives depend on it.

Sage’s Synapse Platform Key to Data Coordination for PsychENCODE Consortium

Image description: Cover image on the Dec. 14, 2018, issue of the journal Science features a neon illustration of a brain. The headline is 'Illuminating The Brain.'
COVER The human brain is the product of myriad molecular and genetic interactions. Here, a neon brain illustration represents individual genetic variability, some of which may lead to disease (denoted by dim or dark segments), as investigated by the PsychENCODE Consortium. This issue sheds light on neurogenetic and epigenetic variation in developing and adult neurotypical brains, as well as in schizophrenia, autism spectrum disorder, and bipolar disorder.
The journal Science today published a special issue, featuring a series of papers from the PsychENCODE consortium.
The PsychENCODE consortium is a NIMH-funded set of grants across 15 institutions that focus on generating genomic and epigenetic data from postmortem brain tissue of individuals diagnosed with neuropsychiatric disorders, developing brains, and cellular model systems. Consortia members share data and insights with each other and the greater research community. Sage Bionetworks, a nonprofit biomedical research and technology development organization founded in Seattle in 2009, functions as the data coordination center for the consortium, using its Synapse platform to share and release data to qualified investigators in the research community. 
 

Synapse tracks collaborative analysis across the PsychENCODE distributed teams, allowing each team to work on the same set of files and to broadcast their research findings in a transparent, reproducible manner. Synapse’s human data governance controls allow the distribution of sensitive human data directly to the broader research community. The PsychENCODE DCC at Sage Bionetworks is responsible for coordinating the upload of data to Synapse from each research project according to grant milestones, and for making the data available according to the Findable, Accessible, Interoperable, Reusable (FAIR) principle

Using Open Technology Platform to Help Develop Community Resource for Mobile Cognitive Tracking

New awards from the National Institute on Aging (NIA) will fund two independent projects to develop a suite of mobile cognitive tests that will be distributed via Sage’s technology platforms for integration into clinical research studies. Designing these remote cognitive assessments on a common technical platform provides a single point of entry for the broader community of researchers, who will be able to benefit from and contribute to the resource more rapidly and efficiently.

Remote cognitive assessments allow researchers to better understand the progression and variation in cognition in the context of daily living, an approach that is not possible with traditional tests performed in the clinic. Importantly, the research teams, led by investigators at Northwestern University and Penn State University are committed to developing the suite of tools on a common, open platform to enable an extensive and dynamic norming framework that will ensure that researchers understand the impact of context on test performance. This will be repeated across at least a half dozen research studies.

Dr. Richard Gerson, of Northwestern University, is leading a consortium of researchers from several institutions including Harvard University and University of California, San Francisco, in the development of the MobileToolbox library of iOS and Android cognitive assessments. Dr. Martin Silwinski, of Penn State University, is leading a second consortium of researchers from several institutions, including Washington University and University of Southern California, to develop accurate and more sensitive measurements for detecting subtle cognitive changes during preclinical states of neurological diseases, such as Alzheimer’s Disease.

Read news article from Penn State University

“By performing this work in the open domain, we create a dynamic resource to share cognitive tests in a manner where the community can independently evaluate their validation and norming criteria,” said Dr. Lara Mangravite, president, Sage Bionetworks. “In this way, clinical researchers will be able to easily identify and deploy cognitive tools that are optimally useful for their own research needs.”

New Research Tools Available in the Search for Therapies for Neurofibromatosis Type 1 (NF1)

New Research Tools Available in the Search for Therapies for Neurofibromatosis Type 1 (NF1) – A collaboration of the Neurofibromatosis Therapy Acceleration Program (NTAP), together with Sage Bionetworks, Johns Hopkins, NCATS and the University of Florida. Read the full article in Scientific Data (June 12, 2018).

 

Press release by Cathy Gara | published by NTAP

Plexiform neurofibromas affect up to 50 percent of people with neurofibromatosis type I (NF1), a rare disease of the nervous system for which there are no approved drug therapies.  NF1 has an incidence of 1/2600 – 1/3000 and arises from mutations in the NF1 gene whose protein, neurofibromin, is normally involved in suppressing cell division.  Without enough working neurofibromin, plexiform neurofibromas can form on nerves throughout the body.  These tumors often appear and grow rapidly throughout childhood. Although they are non-cancerous, their size and location can cause weakness, sensory abnormalities, deformity, and pain, and in some cases, turn malignant.

Plexiform neurofibromas involve several kinds of cells, but they are believed to arise from Schwann cells, a type of neural support cell, that are missing both copies of the NF1 gene.  As with all slow-growing, benign tumors, NF1 tumor cells are hard to grow in the laboratory, limiting the ability of scientists to test potential treatments in reproducible, well-characterized model systems.  In 2016, researchers at the University of Florida figured out how to continuously culture normal and NF1 patient-derived Schwann cells.

Now, a multi-institutional group of scientists from The Johns Hopkins University, the National Center for Advancing Translational Sciences (NCATS), the University of Florida, and Sage Bionetworks has created a new discovery tool.  They characterized, technically optimized and made publicly available a genetically diverse set of patient-derived Schwann cells with a range of NF1 mutations allowing the efficient testing of thousands of drug-cell combinations.  The cells of various NF1 backgrounds were then exposed to 1,912 cancer drugs that are in late stages of clinical development and with known protein targets to assess their ability to prevent the cells from dividing at various doses.  Testing drugs in cells with various patterns of NF1 mutations allows for precision in selecting drugs that are active against the specific cells that cause the tumors, but not bystander cells.

These advances are described in the manuscript “Pharmacological and genomic profiling of neurofibromatosis type 1 plexiform neurofibroma-derived Schwann cells,” published in Scientific Dataon June 12.  The results of this work set the stage for future experiments to: (1) test effective, already-approved drugs for plexiform neurofibromas and other “benign” tumors, (2) discover new pathway interactions that drive tumor growth, and (3) show how cells with different genetic signatures react to various drug combinations.

This work was a major initiative of the Neurofibromatosis Therapy Acceleration Program (NTAP) (www.n-tap.org) a research program based at the Johns Hopkins University School of Medicine.  Dr. Jaishri Blakeley, the Director of NTAP said, “the goal of this project was to create a reliable and fully characterized set of cell culture systems available to all researchers to encourage therapeutic discovery for neurofibromas and thereby fill a big gap in the research landscape.”  All of the data generated has been made openly available and can be accessed through http://www.synapse.org/pnfCellCulture and other sources outlined in the paper.  In addition, the cell culture systems generated are available via the biological materials resource and standards organization, ATCC (https://www.atcc.org).

About the Neurofibromatosis Therapy Acceleration Program (NTAP)

NTAP is a philanthropy driven research organization based at the Johns Hopkins University School of Medicine focused on accelerating the development of therapeutics for NF1 tumors by fostering collaboration, promoting the open and timely sharing of results, and streamlining research models.  The Johns Hopkins University and the University of Florida are academic institutions based in Baltimore, Maryland, and Gainesville, Florida, respectively.

About Sage Bionetworks

Sage Bionetworks is a nonprofit biomedical research organization, founded in 2009, with a vision to promote innovations in personalized medicine by enabling a community-based approach to scientific inquiries and discoveries. Sage Bionetworks strives to activate patients and to incentivize scientists, funders and researchers to work in fundamentally new ways in order to shape research, accelerate access to knowledge and transform human health. It is located on the campus of the Fred Hutchinson Cancer Research Center in Seattle, and is supported through a portfolio of philanthropic donations, competitive research grants, and commercial partnerships. More information is available at www.sagebase.org.

About NCATS

NCATS is a component of the National Institutes of Health (NIH) within the Department of Health and Human Services. NCATS conducts and supports research on the science and operation of translation — the process by which interventions to improve health are developed and implemented — to allow more treatments to get to more patients more quickly. For more information about how NCATS is improving health through smarter science, visit https://ncats.nih.gov. The NIH — the United States’ medical research agency — includes 27 institutes and centers and is the primary federal agency for conducting and supporting basic, clinical and translational medical research. It investigates the causes, treatments and cures for both common and rare diseases. For more information about the NIH and its programs, visit http://www.nih.gov.

For more information

Justin Guinney, PhD

Sage Bionetworks

206-928-8245

justin.guinney@sagebionetworks.org

Leading Cancer Research Organizations Jointly Unveil Comprehensive Immunotherapy Tool to Analyze Interactions Between Tumors and Immune Microenvironment

Cancer Research Institute iAtlas Poised to Improve Patient Outcomes by Providing Researchers Greater Access to Genomics Data

NEW YORK and SEATTLE – April 5, 2018 – The Cancer Research Institute (CRI), Institute for Systems Biology (ISB) and Sage Bionetworks – three organizations on the forefront of cancer immunotherapy, systems biology and bioinformatics –  today announced the release of the Cancer Research Institute iAtlas, a comprehensive web-based tool that allows oncologists and researchers to study and analyze interactions between tumors and the immune microenvironment.

CRI iAtlas is a bioinformatics tool that harnesses immunogenomic data, which were recently published in the journal Immunity. The data are a result of the PanCancer Atlas initiative, the final phase of The Cancer Genome Atlas (TCGA), which investigates more than 10,000 tumor samples across 33 cancer types.

“The Cancer Research Institute, having funded transformative immuno-oncology research for 65 years, decided to support the establishment of an open access database because of the potential impact this tool could have across the field. We expect that the CRI iAtlas will help to accelerate discovery and improve patient outcomes by providing researchers greater access to genomics data to better understand the immunological characteristics of the tumor microenvironment and its potential impact on patient responses to immunotherapy,” said Jill O’Donnell-Tormey, Ph.D., CEO and director of scientific affairs at CRI. “As the CRI iAtlas evolves, we would like to see it become the central repository for this crucial immunogenomics data.”

“The CRI iAtlas tool is the latest iteration of ISB’s focus on providing data resources and visualizations to the research community,” said Ilya Shmulevich, Ph.D., Professor at ISB and a core member of the TCGA and iAtlas projects. “With iAtlas, results from the new TCGA study can be harnessed to investigate the immune responses shared among different types of tumors and to explore how immune responses relate to genomic and clinical phenotypes.”

The iAtlas platform is a community resource that opens up previously difficult-to-obtain insights to research organizations of all sizes.

“We are grateful to CRI and the hundreds of researchers who have contributed to this important resource,” said Justin Guinney, Ph.D., Vice President of Computational Oncology at Sage Bionetworks. “The CRI iAtlas platform provides an intuitive and powerful set of web tools that facilitate data exploration and access to an extensive set of immune characterized samples from TCGA.”

Media contacts
For CRI: Brian Brewer, bbrewer@cancerresearch.org, 212.688.7515 x242
For ISB: Joe Myxter, joe.myxter@systemsbiology.org, 206.732.2157
For Sage Bionetworks:  Justin Guinney, justin.guinney@sagebase.org, 206.667.2102

About the CRI iAtlas

The Cancer Research Institute (CRI) iAtlas (www.cri-iatlas.org) is an interactive web-based platform and set of analytic tools for studying interactions between tumors and the immune microenvironment. These tools allow researchers to explore associations among a variety of immune characterizations as well as with genomic and clinical phenotypes. The initial version of CRI iAtlas is based on an analysis performed by The Cancer Genome Atlas (TCGA) Research Network on the TCGA data set comprising over 10,000 tumor samples and 33 tumor samples (Thorsson et al. Immunity, 2018). In this analysis, each tumor sample was scored for a variety of readouts for immune response, such as immune cell composition, adaptive cell receptor repertoire, neoantigen load, and expression of genes coding for immunomodulatory proteins. The web tool allows research to explore these data readouts, and the relation between them in TCGA tumor types and in overarching immune subtypes identified in the study. The CRI iAtlas is made possible through a collaboration between the Cancer Research Institute, Sage Bionetworks and the Institute for Systems Biology.

About the Cancer Research Institute

The Cancer Research Institute (CRI), established in 1953, is the world’s leading nonprofit organization dedicated exclusively to transforming cancer patient care by advancing scientific efforts to develop new and effective immune system-based strategies to prevent, diagnose, treat, and eventually cure all cancers. Guided by a world-renowned Scientific Advisory Council that includes three Nobel laureates and 26 members of the National Academy of Sciences, CRI has invested $357 million in support of research conducted by immunologists and tumor immunologists at the world’s leading medical centers and universities, and has contributed to many of the key scientific advances that demonstrate the potential for immunotherapy to change the face of cancer treatment. Learn more at www.cancerresearch.org.

About Sage Bionetworks

Sage Bionetworks is a nonprofit biomedical research organization, founded in 2009, with a vision to promote innovations in personalized medicine by enabling a community-based approach to scientific inquiries and discoveries. Sage Bionetworks strives to activate patients and to incentivize scientists, funders and researchers to work in fundamentally new ways in order to shape research, accelerate access to knowledge and transform human health. It is located on the campus of the Fred Hutchinson Cancer Research Center in Seattle, and is supported through a portfolio of philanthropic donations, competitive research grants, and commercial partnerships. More information is available at www.sagebase.org.

About the Institute for Systems Biology

The Institute for Systems Biology is a nonprofit biomedical research organization based in Seattle. It was founded in 2000 by systems biologist Leroy Hood, immunologist Alan Aderem, and protein chemist Reudi Aebersold. ISB was established on the belief that the conventional models for exploring and funding breakthrough science have not caught up with the real potential of what is possible today. ISB serves as the ultimate environment where scientific collaboration stretches across disciplines and across academic and industrial organizations, where our researchers have the intellectual freedom to challenge the status quo, and where grand visions for breakthroughs in human health inspire a collective drive to achieve the seemingly impossible. Our core values ensure that we always keep our focus on the big ideas that eventually will have the largest impact on human health. ISB is an affiliate of Providence St. Joseph Health, one of the largest not-for-profit health care systems in the United States.