Completed LINCS program generated dataset to help understand how cells function
As we approach the heart of summer, the federal government is starting discussions about having its staff return to the physical workspace. This includes NIH drafting its plans for safely managing the transition from the current COVID-19 policies related to staff density at NIH facilities. The increased use of telework over the last 17 months will undoubtedly result in some changes to how NIH staff members function, as (like for many aspects in society) we begin defining a “new normal” for our work and lives.
Also, in last month’s The Genomics Landscape, I reported my intention to appoint Vence Bonham Jr., J.D. as the NHGRI acting deputy director. I am pleased to announce that this appointment is now official!
All the best,
Completed LINCS program generated dataset to help understand how cells functio
The Library of Integrated Network-based Cellular Signatures (LINCS) program, a National Institutes of Health (NIH) Common Fund project, has completed its goal of creating a large-scale, systematically generated molecular and cellular dataset to help scientists understand how cells respond to specific biological and environmental stressors. The basic components of the human body involve many biological systems working together to sustain development and health. Recognizing how these pieces work normally and identifying the factors that disrupt normal function is a central challenge in biomedical research. To aid efforts, the LINCS program examined the role of drugs and other biological agents and their effects on the development of a cell’s normal state. In addition, LINCS developed a resource library of molecular “signatures” that reflect the responses that different cell types show under different conditions.
LINCS was based on the notion that disrupting any one of the many steps of a biological process will cause related changes in the molecular and cellular characteristics, behavior, and/or function of a cell. In the past, most research studies designed to interpret cellular responses have focused on specific treatments related to disease or have been limited in other ways. While informative, studies that take into account multiple chemical and environmental conditions are crucial for understanding the full range of biological complexity. LINCS aimed to do just that. Since the program’s launch in 2010, 15 LINCS-funded institutions in the United States have developed datasets and software to analyze the consequences of perturbing agents (e.g., small molecules, genetic alterations, antibodies, and microenvironmental changes) on cellular function and response.
Now at a completed state, the LINCS legacy represents an impressive data and software resource. The associated dataset contains over 3 million profiles, with information about over 40,000 small molecules and genetic-perturbing agents, over 1,100 human cell types, and 1,500 proteins. Importantly, the LINCS dataset is being actively used. In 2019 alone, nearly 60 LINCS data-analysis and -visualization tools have been used by more than 200,000 unique users in over 600,000 independent computational sessions. LINCS data can be found on the Data Coordination and Integration Center (DCIC) website. LINCS data and ways to access them for the long term are being made possible by the Common Fund Data Ecosystem (CFDE). LINCS researchers have also generated over 200 publications, and LINCS assets have been cited in many publications by non-LINCS researchers — an indication of the dataset’s growing utility for studies of human biology.
LINCS has had a major impact on the research community. In addition to the impressive usage statistics above, several small and large pharmaceutical companies (e.g., AstraZeneca, Genentech, and Novartis) have created their own LINCS-related low-cost gene-profiling technologies, and Novartis has even leveraged the DCIC’s computational framework for internal use.
LINCS-affiliated groups currently have contracts from two pharmaceutical companies to collaborate. This industrial collaboration will lead to additional LINCS-related data production and help in the storage of LINCS data. A major use of some of the LINCS data is developing new pharmaceuticals or repurposing existing ones for use in treating new diseases. Both LINCS data and approaches have found a large user base within the drug discovery community (academic and industrial). This has come about through a number of successful collaborations between LINCS investigators and pharmaceutical companies.
LINCS held a successful final symposium in November 2020, which attracted over 700 attendees. This two-day event highlighted LINCS’s impact on the research community by featuring work from both LINCS investigators and external researchers leveraging LINCS resources. Each day included a series of workshops showcasing ways to access and use LINCS resources.
Finally, since 2015, NIH has funded over 160 grant awards proposing ways for using LINCS data in the study of specific diseases and biological processes (not including grants to LINCS investigators themselves). Such a response helps to demonstrate that LINCS has moved large-scale perturbational studies into the scientific mainstream. LINCS data and tools are publicly available and will continue to serve as a community resource to aid the broader biomedical enterprise.
NHGRI and NCI award $33 million to improve utility of polygenic risk scores in diverse populations
NHGRI and the National Cancer Institute (NCI) are partnering to fund grants totaling $38 million over five years to establish and support the Polygenic Risk MEthods in Diverse populations (PRIMED) Consortium. NHGRI will fund six of the awards for $33 million, while NCI will fund a seventh participating award for $5 million. The awards will support research that aims to develop and establish robust methods for improving the way that polygenic risk scores (PRS) can be used to predict disease in ancestrally diverse communities. PRIMED will provide the research community with information that will allow the development of clinical trials to test the utility of PRS. Also, the study and use of PRS has largely focused on people of European ancestry. The new consortium will specifically address this gap by refining approaches for generating and using PRS in a fashion that makes them more applicable to diverse populations.
Upcoming conference to explore history and philosophy of biology and genetics
On July 29, the NHGRI History of Genomics Program will host a one-day conference entitled “From the ‘Baldwin Effect’ to Genes of Small Effect: Celebrating the Work of David Depew” to explore and celebrate the work of David Depew, Ph.D., Professor Emeritus at the University of Iowa. David Depew was among the first historians and philosophers of biology and genetics. The conference will have noted scholars develop themes that emanate from Dr. Depew’s work across several areas of the history and philosophy of biology. Some of these areas will include: the evolutionary synthesis; adaptation in modern biology and genetics; issues of race and genetic exceptionalism; the status of the evolutionary synthesis after the Human Genome Project; and recent work in human genomic variation.
Promote robust and consistently applied standards in genomics research — the use of carefully defined standards (for example, those for generating, analyzing, storing, and sharing data) has benefited genomics in numerous ways, and this must include appropriate privacy and data-security protections for those participating in genomics research.
“My research program revolves around a cohort of patients with various inflammatory disorders, some of whom we understand at a molecular genetic level, others of whom we don’t (at least yet). The success of this enterprise to discover new disease genes, to understand how they work, and to develop new therapies that effectively target the pathways we discover – all that is grounded in a sacred bond of trust between our investigative team and our patients, extending to humanity at large. And that trust, in turn, is built upon the scientific and ethical standards that the genomics community has carefully crafted and explicitly articulated over the last three decades.”
Dan Kastner, M.D., Ph.D. (Director, NHGRI Division of Intramural Research)
COVID-19 News and Research
Request for Information
NIH & NHGRI News
Seminar Series: Bold Predictions for Human Genomics by 2030
Session 6: July 12, 2021, 3 p.m. to 4:30 p.m. ET
Prediction: The regular use of genomic information will have transitioned from boutique to mainstream in all clinical settings, making genomic testing as routine as complete blood counts (CBCs).
- Jennifer Posey, M.D., Ph.D., Baylor College of Medicine
- Katrina Armstrong, M.D., Massachusetts General Hospital & Harvard Medical School
- Teri Manolio, M.D., Ph.D., NHGRI
About The Genomics Landscape
A monthly update from the NHGRI Director on activities and accomplishments from the institute and the field of genomics.
Last updated: July 8, 2021