NIH awards Brown $10.8M to expand data-informed research to fight human disease

The COBRE Center for Computational Biology of Human Disease is advancing the use of computational tools among biomedical scientists at Brown, helping them unlock new insights that could ultimately benefit patients.

Five years after an $11.5 million federal grant launched the COBRE Center for Computational Biology of Human Disease at Brown University, the National Institutes of Health has awarded $10.8M in new funds to Brown to build on the center’s early success.

The center — a federal Center of Biomedical Research Excellence funded by the NIH’s National Institute of General Medical Sciences — uses sophisticated computer analyses to advance research aimed at understanding and fighting human diseases.

Director David Rand, a professor of biology at Brown, said the renewal funds will enhance the center’s research infrastructure, enable strengthened collaboration among scientists working with computational and bioinformatics tools, and support four new research projects. Rand said there is a “computational revolution” happening in the biomedical sciences, as researchers need computational analyses to help them make sense of massive amounts of available data.

“Even those working in wet labs or clinics who don’t use computers in their daily work will at some point need assistance in analyzing complex data sets,” he said.

Rand compared the current moment to the molecular biology revolution that’s been changing science since the 1970s, when DNA cloning and sequencing became standard tools used by researchers across diverse fields. Computational analysis is bringing groups together today in a similar way, he said. For example, people working in engineering, computer science, basic biology and medicine will face situations where they need to convert data sets into information that can help them find solutions and answer questions. While their research projects are highly distinct, he said, the data analysis work shares common themes.

“In addition to helping researchers with individual projects, we view the Center for Computational Biology of Human Disease as a vehicle for raising the level of computational ability for researchers in the community overall,” Rand said.

To provide that service to COBRE project leaders and researchers across Brown, the center is home to a Computational Biology Core — a group of four scientists, data analysts and software engineers who support data-intensive research. With the renewal grant, center leaders will work to build sustainable support for the group through continued funding to its scientists and support to ensure that four members are at the Ph.D.-level (past budget included support for two Ph.D.s and two master’s-level scientists).

“Everyone has large data sets and needs to convert these into useful information, and we aim to help people achieve that goal,” Rand said. “The center brings together researchers in the lab and clinic with exceptionally skilled and creative data scientists to turn data into information.”

Funds from the grant will also support the research of junior faculty investigators and help position them to earn additional, longer-term funding for their work — enabling them, Rand said, to build upon discoveries and continue their research while freeing up center funds to seed innovative new projects. With the initial $11.5 million from the NIH in the center’s first phase, faculty projects at the Center for Computational Biology of Human Disease generated an additional $17.9 million in grants in areas of research such as human genomics, immunology and infectious disease, microbiome and machine learning approaches to complex genetics.

“That’s the equivalent of a ‘return on investment’ of 150%, and we’re really proud of their success,” Rand said. “What’s also been really gratifying is the fact that some of these researchers had relatively little bioinformatics experience prior to coming to Brown, and they have since added that capacity to their set of lab research tools.”

As examples, Rand cited faculty members Shipra Vaishnava and Amanda Jamieson in molecular microbiology and immunology, both of whom were project leaders on the Phase 1 COBRE grant studying immune function in relation to the microbiome and infectious disease. Working with students in their respective labs and the Computational Biology Core, they developed enhanced computational and bioinformatics analyses for their research, which in turn helped them obtain health-related research grants from the NIH.

Another key success of the center’s five years has been the establishment of a mentoring system that matches investigators with a clinical or laboratory advisor as well as a computational and statistical advisor, an approach that Rand notes will expand in Phase 2. He said that not only encourages multi-disciplinary collaboration but has enabled the center to create a talent pipeline in which project leaders advance toward receiving independent funding for their projects.

In one example, Sohini Ramachandran, a professor of ecology and evolutionary biology at Brown who develops new computational methodologies to identify risk genes for leukemia that differ in incidence across ethnic groups and genders, started as a project leader in 2016. She is now Director of Brown’s Data Science Initiative and a co-leader of the Computational Biology Core, and is mentoring the next generation of scientists in this COBRE program.

The new grant will also fund four new faculty-led projects:

  • Lalit Beura, an assistant professor of microbiology and immunology, will study antiviral T cells in the female reproductive tract to learn more about the mechanisms promoting the function of this newly recognized T cell population, which has potent antipathogenic properties — with the long-term goal of improving vaccine design against pathogens that target this area. His mentors are Laurent Brossay, a professor of molecular microbiology and immunology, and Zhijin Wu, a professor of biostatistics and co-leader of the Computational Biology Core.
  • Ian Wong, an assistant professor of engineering, pathology and laboratory medicine, will model the process of how circulating tumor cells shed from primary tumors metastasize to distant tissues at different rates. He will work with Jonathan Reichner, a professor in the Department of Surgery at the Warren Alpert Medical School and Rhode Island Hospital, and Paul Bertone, an associate professor of medicine (research) and a director in the cancer biology group at Rhode Island Hospital.
  • George Lisi, an assistant professor of molecular biology, cellular biology and biochemistry, will integrate biochemical assays and structural/computational analyses and apply them to questions about the CRISPR-Cas9 protein, a promising tool for precision medicine and bioengineering. His mentors are Arthur Salomon, a professor of biology, and Gerwald Jogl, an associate professor of biology.
  • Ritambhara Singh, an assistant professor of computer science, will focus on using novel machine learning approaches to understand aberrant gene expression in disease states. She is working with Erica Nicole Larschan, an associate professor of molecular biology, cellular biology and biochemistry, and Ramachandran.

To increase diversity and inclusion in the Computational Biology Core and the center more broadly, the grant will also enable a summer internship program for graduate and undergraduate students from groups historically underrepresented in STEM fields.

Brown and its affiliated hospitals have earned prior COBRE grants for research in areas ranging from human behavior to stem cells to skeletal health. Following the initial five-year award, COBRE grants can be renewed for an additional two five-year periods. This Phase 2 award marks the first renewal of Brown’s COBRE Center for Computational Biology of Human Disease. (Award No. 2P20GM109035).

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