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NCI Inks Eight MOUs for International Collaborations in Proteogenomics Research

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NEW YORK (GenomeWeb) – The National Cancer Institute has signed eight new Memoranda of Understanding (MOUs) and Memoranda of Cooperation (MOCs) focused on proteogenomics research.

The new MOUs/MOCs, which fall under the umbrella of the US Cancer Moonshot program, establish relationships for proteogenomics collaborations between the National Cancer Institute and 15 institutions in eight countries, including McGill University, the University of Victoria, and the University of British Columbia in Canada; the Leibniz Institute for Analytical Sciences in Germany; Fudan University and the Shanghai Institute of Materia Medica in China; the Korea Institute of Science and Technology in South Korea; the American Institute in Taiwan/Taipei Economic and Cultural Representative Office and Chang Gung University in Taiwan; and the ETH Zurich in Switzerland.

According to the NCI, the memoranda will establish collaborations to "facilitate the sharing of cancer‐associated clinical research data, genetic and other molecular information (DNA, RNA, and proteins), targeted tests, medical imaging, and subsequent public dissemination of products and data for use by cancer researchers and physicians around the world."

What the agreements mean in concrete terms is still being worked out, Henry Rodriguez, director of the Office of Cancer Clinical Proteomics Research at NCI, told GenomeWeb.

The first goal of the MOUs "is to raise awareness, promote interest, and coordinate activities in the emerging science of proteogenomics," he said.

The key "common denominator" of the collaborations will be the use of proteogenomics, he added.

"Each participant pursues commonly diagnosed cancers in their respective nation," Rodriguez said. "Genomic, proteomic, and imaging data will be shared through NCI's Genomic Data Commons, NCI’s CPTAC Proteomic Data Portal, and NCI’s Cancer Imaging Archive.  In addition, partnerships [will] include training and exchanging proteogenomic data scientists between the participants."

Rodriguez added that several of the MOUs signees met during the Human Proteome Organization's annual meeting last month in Taiwan and discussed elements of the collaboration including the "importance of standardization and harmonization of analytics and informatics to ensure quality data production."

He said that the attendees hoped to meet again in the spring of 2017 to begin establishing concrete research plans.

One likely model for the collaborations is the NCI's Clinical Proteomic Tumor Analysis Consortium, which Rodriguez leads. Since its initial phase, launched in 2006, the project has moved to a focus on proteogenomics, with participants performing protein biomarker discovery and verification studies in tumor tissue samples previously characterized at the genomic and transcriptomic level by the NCI's Cancer Genome Atlas (TCGA) team.

The initiative's third stage, which is slated to start this year and continue through 2021, will continue this proteogenomic bent while also moving in a more translational direction with the establishment of three Proteogenomics Translational Research Centers (PTRCs) that will aim to use genomic and proteomic data to better understand patient drug response and the development of resistance.

The recent MOUs further indicate NCI's commitment to this proteogenomic approach.

While gene and protein expression are obviously related, they can diverge in significant ways. The hope underpinning proteogenomics is that analyzing the two types of molecular information together will prove more informative than looking at them separately.

For instance, a challenge presented by modern sequencing approaches is interpreting the large numbers of genomic alterations such methods can find, distinguishing between meaningful changes that drive disease and changes that happen to be present but are not driving disease.

Integrating proteomic analyses is a possible way to do that. Because proteins are the functional molecules that mediate many biological processes, a genetic mutation that leads to an actual change at the protein level is more likely to be disease-related than one that doesn't lead to protein changes.

Additionally, past studies have shown that potentially meaningful proteomic changes are not always present at the genomic level, which suggests information that could enable better targeted treatments might be missed without proteomic analysis.

Rodriguez noted that in addition to the eight MOUs, NCI has also established a collaboration under the Cancer Moonshot program between CPTAC, the Department of Defense, and the Veteran Affairs Health System called APOLLO (Applied Proteogenomics Organizational Learning and Outcomes).

That program will begin with proteogenomic analysis of 8,000 lung cancer patients from the US Department of Veterans Affairs and Department of Defense systems with the ultimate goal of building a system in which VA and DoD cancer patients routinely undergo genomic and proteomic profiling with the goal of matching their tumor types to targeted therapies.