UVA develops tools to advance genomics, cancer research

University of Virginia School of Medicine scientists have developed resources to advance genomics and cancer research. 

UVA’s Chongzhi Zang and his colleagues and students have developed a computational method to map the folding patterns of our chromosomes in three dimensions from experimental data. 

Using their new approaches, Zang and his colleagues and students have discovered useful data, and they are making their techniques and findings available to their fellow scientists. To advance cancer research, they built an interactive website that brings together their findings with data from other resources. 

The website is bartcancer.org. 

 “The folding pattern of the genome is highly dynamic; it changes frequently and differs from cell to cell. Our new method aims to link this dynamic pattern to the control of gene activities,” Zang, a computational biologist with UVA’s Center for Public Health Genomics and UVA Cancer Center, said in a statement. “A better understanding of this link can help unravel the genetic cause of cancer and other diseases and can guide future drug development for precision medicine.”

Zang’s new approach to mapping the folding of our genome is called BART3D. Essentially, it compares available three-dimensional configuration data about one region of a chromosome with many of its neighbors. 

It can then extrapolate from this comparison to fill in blanks in the blueprints of genetic material using “Binding Analysis for Regulation of Transcription”, or BART, a novel algorithm they recently developed. The result is a map that offers unprecedented insights into how our genes interact with the “transcriptional regulators” that control their activity. Identifying these regulators helps scientists understand what turns particular genes on and off.

The researchers have built a web server, BARTweb, to offer the BART tool to their fellow scientists. It’s available, for free, at http://bartweb.org. The source code is available at https://github.com/zanglab/bart2. 

Test runs demonstrated that the server outperformed several existing tools for identifying the transcriptional regulators that control particular sets of genes, the researchers report.

The UVA team also built the BART Cancer database to advance research into 15 different types of cancer, including breast, lung, colorectal and prostate cancer. Scientists can search the interactive database to see which regulators are more active and which are less active in each cancer.

“While a cancer researcher can browse our database to screen potential drug targets, any biomedical scientist can use our web server to analyze their own genetic data,” Zang said. “We hope that the tools and resources we develop can benefit the whole biomedical research community by accelerating scientific discoveries and future therapeutic development.”

The researchers have published their findings in a trio of new scientific papers: They describe BART3D in Bioinformatics in an article by Zhenjia Wang, Yifan Zhang and Chongzhi Zang; they describe BARTweb in NAR Genomics and Bioinformatics in an article by Wenjing Ma, Zhenjia Wang, Yifan Zhang, Neal E. Magee, Yayi Feng, Ruoyao Shi, Yang Chen and Chongzhi Zang; and they describe BART Cancer in NAR Cancer in a paper by Zachary V. Thomas, Zhenjia Wang and Chongzhi Zang.

Chongzhi Zang is a member of the School of Medicine’s Department of Public Health Sciences and Department of Biochemistry and Molecular Genetics. He is also part of UVA’s Department of Biomedical Engineering, a collaboration of the School of Medicine and the School of Engineering.