CSER consortium ends after twelve years of groundbreaking research

Since 2011, the Clinical Sequencing Evidence-generating Research (CSER) consortium has worked to offer patients and their families, healthcare systems, and policymakers a clearer understanding of the opportunities and challenges of implementing genomic medicine in diverse populations and settings. After twelve years of groundbreaking research about advancing genomics in the clinic, the CSER program ended in June 2023.

Over the past two decades, the power of genome sequencing has become evident in disciplines like biology, evolution, forensics, and ancestry. But one of the most relevant areas for humanity is the use of genome sequencing in medicine; that is, genomic medicine (a growing medical discipline that involves using a person’s genomic information as part of their clinical care). However, there are many potential barriers to implementing genomic medicine, and the CSER program has conducted research aiming to overcome these barriers.

The first phase of CSER, then called the Clinical Sequencing Exploratory Research program, began when NHGRI partnered with the National Cancer Institute (NCI) to fund six research sites to ease the adoption of genome-sequencing methods in medicine, guide the development and dissemination of best practices for the integration of genomic information in clinical care, and examine the ethical, legal, and psychosocial implications of bringing genomic data into clinical decision-making. This included, for example, evaluation of the risks and benefits associated with the return of incidental findings and information on genomic variants of uncertain effect.

In mid-2013, the CSER consortium added three more clinical sites and one coordinating center in addition to incorporating the nine projects formerly comprising the ELSI Return of Results Consortium. Investigators from the NHGRI intramural ClinSeq™ project also participated. In August 2017, NHGRI partnered with NCI and the National Institute on Minority Health and Health Disparities (NIMHD) to launch the second phase of CSER, renamed the Clinical Sequencing Evidence-Generating Research consortium. CSER researchers moved from “exploratory” research to “evidence-generating” research, focusing on accelerating the diagnostic process and investigating what is effective in improving outcomes and patient care. To broaden the applicability of the generated evidence, CSER researchers emphasized the inclusion of diverse populations (i.e., populations that traditionally experience health disparities) and populations that receive clinical care outside of specialized academic medical centers.

The second phase of CSER included six clinical sites, the NHGRI intramural ClinSeq™ project, and a coordinating center. As of June 2022, CSER phase 2 had recruited < 5,200 participants, 75% of whom were from underserved populations.

Although funding for CSER is now over, investigators are still working to write manuscripts addressing several topics that represent well the overall goals of the program. These topics include clinical utility of returning genomic testing results, experiences with family communication of genomic test results, challenges with reporting incidental findings for pediatric patients, resources required to implement new genetic testing tools, pediatric neurodevelopmental phenotypes, and engaging underrepresented stakeholders in genomic research.

After its dozen years of productive work, CSER’s legacy includes many notable accomplishments. The program embedded multiple disciplines in the implementation of genomic medicine and engaged diverse patients and healthcare settings. It helped to create standardized genome sequencing practices and increased knowledge of how genomic variation influences health. It examined how clinical management changes based on new genomic information and how such information leads to improved health outcomes.

Since its inception, CSER has aimed to generate evidence supporting the clinical utility of genome sequencing, with a major emphasis on diverse patient populations and healthcare settings. It is largely regarded as an exemplar among the genomic medicine research programs funded by NHGRI. While the funding for CSER has ended, the type of research it conducted and the clinical practices it advocated for continue to be widely disseminated.

NHGRI, in partnership with the National Cancer Institute (NCI) and the National Institute of Environmental Health Sciences (NIEHS), is awarding $50.3 million over five years to establish the Multi-Omics for Health and Disease Consortium. “Multi-omics” refers to a research approach that generates and analyzes several “omics” data types derived by different technologies — such as genomics, epigenomics, transcriptomics, proteomics, and metabolomics. Each of these data types reveals distinct information about different aspects of biology. This approach has great potential for making clinical breakthroughs by gaining a more holistic view of health and disease. The consortium will enroll participants from ancestrally diverse backgrounds to examine multi-omic “signatures” of conditions such as fatty liver disease, hepatocellular carcinoma, asthma, chronic kidney disease, and preeclampsia. The consortium also aims to develop scalable and generalizable multi-omics research strategies to be used by other researchers.

NHGRI and the American Society of Human Genetics (ASHG) are delighted to announce that the ASHG-NHGRI Genomics and Public Service Fellowship Program is now accepting applications through November 30, 2023. The program will provide early-stage professionals with experiences and professional development relevant for a range of genomics careers. Through this program, participants will work at ASHG, NHGRI, and/or additional locations to gain valuable skills for various careers in genetics and genomics. The program is designed for two groups of fellows, one for those at the graduate level and one for those at the postbaccalaureate level. The graduate-level group will build upon an existing partnership with ASHG, involving the Genetics and Public Policy Fellowship and the Genetics Education and Engagement Fellowship, which have already trained dozens of fellows (including some current NHGRI staff!); now, a new component, the Genomics Communications Fellowship, has been added and will offer experiences in the swiftly changing science media landscape relevant to genomics. The postbaccalaureate group will involve a new ASHG-NHGRI Post-baccalaureate Genomics Analyst Fellowship, which will provide recent college graduates with training in the oversight and administration of research-funding programs at the forefront of genomics and in the leadership of the fields of human genetics and genomics at ASHG.

The NIH Cloud Platform Interoperability (NCPI) effort and the Human Pangenome Project have been selected as a Global Alliance for Genomics and Health (GA4GH) Driver Projects. GA4GH Driver Projects are real-world genomic data initiatives that help develop and pilot GA4GH standards and tools. The goal of the NCPI is to implement guidelines and technical standards to create a trans-NIH, cloud-based, federated data ecosystem to facilitate end-user analyses across participating cloud platforms. NCPI was launched in late 2019 and operates as a collaboration of the NHGRI Analysis Visualization and Informatics Lab-space (AnVIL) program and other NIH cloud-based programs and resources. The Human Pangenome Project (HPP) is an international alliance of genomics partners that aims to provide accessible high-quality genome sequences that represent the diversity of the human population. The HPP partners have adopted GA4GH principles, enabling responsible genomic data sharing within a human rights framework.

Sara Chandros Hull, Ph.D., and Shawn Burgess, Ph.D., were appointed new Deputy Scientific Directors in the NHGRI Intramural Research Program (IRP). They are replacing Paul Liu, M.D., Ph.D., who has served as the Deputy Scientific Director for nearly 12 years. Dr. Liu’s wisdom, expertise, and level-headedness have been profoundly impactful and appreciated at NHGRI. Dr. Hull joined the NIH 24 years ago and is currently an Associate Investigator in the NHGRI Office of Scientific Core Facilities, Director of the NHGRI Bioethics Core, and the Chair of the NIH Intramural Institutional Review Board. Dr. Burgess has been with NHGRI for 22 years and serves as Senior Investigator in the Translational and Functional Genomics Branch, specifically as Head of the Developmental Genomics Section. As Deputy Scientific Directors, Drs. Hull and Burgess will be primary advisors to NHGRI Scientific Director Charles Rotimi, Ph.D., helping to oversee the operations of the offices, facilities, centers, and programs within the NHGRI IRP. They will also help foster collaborations among intramural investigators, facilitate quadrennial reviews of each intramural investigator, and help liaise between the institute and broader NIH. Drs. Hull and Burgess began their appointment on October 1, 2023.

The New York Academy of Medicine recently awarded the Academy Medal for Distinguished Contributions in Biomedical Science to NHGRI Scientific Director, Charles Rotimi, Ph.D.. The award recognizes researchers with sustained and impactful accomplishments in the biomedical field and a commitment to translating these findings to advance human health. The academy conferred this award to Dr. Rotimi for his leadership in spearheading numerous programs to improve ancestral diversity in research participants and in the scientific workforce as well as his research in genetic epidemiology. He was honored at a virtual event held by the New York Academy of Medicine on September 27, 2023.

Ellen Sidransky, M.D., Chief of the NHGRI Medical Genetics Branch, will be awarded the 2024 Breakthrough Prize for her discoveries about the genetics of Parkinson’s disease, a central nervous system disorder that affects movement. Dr. Sidransky and her research group identified mutations in the GBA1 gene as a risk factor for Parkinson’s disease by uncovering connections between Parkinson’s and a rare genetic condition called Gaucher disease, which is caused by mutations in the same gene. The discovery of GBA1 mutations as a risk factor for Parkinson’s disease is an important step in understanding the development and progression of this condition. While some treatments are available, there is currently no cure for Parkinson’s disease or Gaucher disease. Understanding the involved biological pathways will be important for future studies aiming to develop better treatments for these conditions.

William Pavan, Ph.D., senior investigator in the Genetic Disease Research Branch and head of the Genomics, Development and Disease Section within NHGRI’s Intramural Research Program, retired at the end of September. For nearly 30 years, Bill led a research group that aimed to understand genome function and gene pathways in development and disease. His group was the first to discover a transcription factor for tissue and organ formation during development that is associated with melanoma and Waardenburg syndrome type 4. His team also helped to identify the lysosomal transmembrane protein whose mutation results in Niemann-Pick disease, type C1. A scientific symposium was held at NHGRI in Bill’s honor at the end of September.