Genomic rearrangements in cancer cells produce fusion transcripts, which may give rise to chimeric protein products not present in normal cells. In addition, cancer cells can express alternate forms of encoded messages that give rise to protein variants different from normal tissue. These chimeras and protein variants can serve as robust diagnostic markers or drug targets. Moreover, ongoing research efforts are beginning to unveil the potential clinical relevance of these variant RNA products. Increasing the “alterome” of tumors by fully characterizing their RNA landscapes will expand our understanding of cancer mechanisms, provide new biomarkers and reveal possible new RNA-based therapeutics, thus improving personalized patient treatment.
“Predicting RNA species in a cancer cell is a particularly challenging task,” says Josh Stuart, Professor at the UC Santa Cruz Genomics Institute and one of the challenge leaders. “RNA expression reflects much of the deranged complexity of the underlying cancer cell DNA and then adds another level of derangement on top of that.”
The goal of the SMC-RNA Challenge is to identify the best methods for detecting rearrangements in RNA sequencing (RNA-seq) data. Sub-challenges are focused on detecting and quantifying mRNA fusions and isoforms. Methods will be evaluated with both in silico and spiked-in data. Two key questions that will be addressed are: 1) What is the best way to estimate the abundances of a set of known RNA isoforms? and 2) What is the best way to predict the presence of novel gene fusions? Both of these questions will involve in silico generated and wet lab spiked-in RNA sequencing data.Like the SMC-Het challenge, contestants will contribute their code as self-contained virtual machines that can be run by the challenge administrators. The contestant code will then be executed on one of the three NCI Cloud Pilots that have been established to facilitate analysis of large-scale cancer genomics datasets.
The Cancer Genomics Cloud Pilots are designed to explore innovative methods for accessing and computing on large genomic data. They aim to bring data and analysis together on a single platform by creating a set of data repositories with co-located computational capacity and an Application Programming Interface (API) that provides secure data access. The goals of the Cloud Pilots are to democratize access to NCI-generated genomic and related data and to create a cost-effective way to provide computational support to the cancer research community. Three contracts were awarded to develop the Cloud Pilots, to the Broad Institute (https://portal.firecloud.org/), the Institute for Systems Biology (https://isb-cgc.appspot.com/), and Seven Bridges Genomics (https://cgc.sbgenomics.com/). Each of these groups is developing infrastructure and a set of tools to access, explore, and analyze molecular data.
“NCI is intrigued by the potential of the DREAM challenge. Leveraging the Cloud Pilot concept to enable crowdsourcing to improve cancer transcript detection and quantification shows the kind of significant impact the cloud-based infrastructure can have,” reports Tanja Davidsen, a Biomedical Informatics Program Manager at NCI.
The challenge will initially leverage cloud compute available from the Institute for Systems Biology and then expand to include those provided by Seven Bridges and the Broad Institute. SMC-RNA is based on the containerized software and portable workflow descriptions. As such, upon completion, any compatible cloud system also will be able to replicate the execution and evaluation of all submitted code.
To motivate a high level of collaboration, Sage Bionetworks’ Synapse platform provides leaderboards, the ability for teams to dynamically form and re-form as the Challenge proceeds, and a discussion forum where participants can share ideas. As an added incentive, all individuals and teams that submit a final model will be invited as consortium co-authors on an overview paper of the Challenge that will be submitted to Nature Biotechnology, as the official journal partner of the Challenge. Top performers will receive travel awards and speaking invitations to the 2017 DREAM Conference.
“It is an exciting development to see several technologies converge on this challenge so elegantly,” says Kyle Ellrott, researcher with the OHSU Knight Cancer Institute, assistant professor at the OHSU School of Medicine, and one of the challenge leaders. “The cloud pilots are available to provide access to scalable compute to large datasets. With the SMC-Het, and now SMC-RNA, we employ an evaluation mechanism that produces reproducible bioinformatics methods. The results of these challenges can be used to solve important problems in cancer genomics. And at the end of the challenge any of the submitted techniques could be made available to the users the cloud pilots for them to apply to their own data. It is truly a dynamic combination that is set to accomplish great things.”
The Ontario Institute for Cancer Research (OICR) is the central coordinating agency of the DREAM Challenge, led by Dream Challenge Director Dr. Paul Boutros of OICR.
About the OHSU Knight Cancer Institute
The Knight Cancer Institute at Oregon Health & Science University is a pioneer in the field of precision cancer medicine. The institute's director, Brian Druker, M.D., helped prove it was possible to shut down just the cells that enable cancer to grow. This breakthrough has made once-fatal forms of the disease manageable and transformed how cancer is treated. The OHSU Knight Cancer Institute is the only National Cancer Institute-designated Cancer Center between Sacramento and Seattle – an honor earned only by the nation's top cancer centers. It is headquarters for one of the National Cancer Institute's largest research collaboratives, SWOG, in addition to offering the latest treatments and technologies as well as hundreds of research studies and clinical trials. For additional information on the OHSU Knight Cancer Institute visit www.ohsu.edu/xd/health/services/cancer or follow us on Facebook and Twitter.
About the UC Santa Cruz Genomics Institute
Genomics is revolutionizing biology, ecology, agriculture, forensics, and many other fields while initiating a new era of precision medicine. The mission of the UC Santa Cruz Genomics Institute is to unlock the world’s genomics information to gain a deeper understanding of life and to drive the targeted treatment of diseases. The institute aims to pull together genomics researchers from a variety of disciplines across academic divisions, with the goal of cross-pollinating ideas, methodologies and research, and leading to new collaborations and synergies. Institute faculty have research foci in Health and Conservation. Both programs are built around a platform for advancing sequencing technologies and a software effort that will provide integrated data analysis.
About Ontario Institute for Cancer Research
OICR is an innovative cancer research and development institute dedicated to prevention, early detection, diagnosis and treatment of cancer. The Institute is an independent, not-for-profit corporation, supported by the Government of Ontario. OICR and its funding partners support research programs that involve more than 1,700 investigators, clinician scientists, research staff and trainees in research institutes and in universities across the Province of Ontario as well as at its headquarters. OICR has key research program efforts underway in small molecules, biologics, stem cells, imaging, genomics, informatics and biocomputing. For more information visit www.oicr.on.ca
About Washington University School of Medicine
Washington University’s 2,100 employed and volunteer faculty physicians also are the medical staff of Barnes-Jewish and St. Louis Children’s hospitals. The School of Medicine is one of the leading medical research, teaching and patient-care institutions in the nation, currently ranked sixth in the nation by U.S. News & World Report. Through its affiliations with Barnes-Jewish and St. Louis Children’s hospitals, the School of Medicine is linked to BJC HealthCare.
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. In pursuit of this Mission, Sage Bionetworks is working with others to assemble an information Commons for biomedicine that (1) is supported by an open compute space (Synapse: http://www.synapse.org), (2) supports open research collaborations and innovative DREAM Challenges, and (3) empowers citizens and patients with the tools to partner with researchers and share their data through Sage's BRIDGE platform in order to drive the research studies that matter most to them.
About DREAM Challenges
The Dialogue on Reverse Engineering Assessment and Methods (DREAM) Challenges pose fundamental questions about systems biology and translational medicine. A. Califano (Columbia University) and Gustavo Stolovitzky (IBM Research and the Icahn School of Medicine at Mount Sinai) founded the group in 2006. The DREAM Challenges, designed and run by a community of researchers from a variety of organizations, invite participants to propose solutions while fostering collaboration and building communities in the process. Expertise and institutional support are provided by Sage Bionetworks, along with the infrastructure to host challenges via their Synapse platform.
Contacts:
Sage BionetworksThea Norman, 206-667-3192Mobile: 858-997-8598[email protected]
OHSUAmanda Gibbs503.494.5640[email protected]
UCSCTim Stephens831-459-4352[email protected]
OICRRhea Cohen, 416-673-6642[email protected]
Washington University School of MedicineJudy Martin Finch314-286-0105[email protected]
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