Brown professor Vivian Cheung is one of the founding members of the consortium.

The Human Genome Project was a 13-year effort to generate the first ever complete sequence of all human DNA, widely regarded as one of science’s greatest feats in recent history. Now, Brown researchers are leading the charge on making its complement: a complete sequence of all human RNA.

This summer, the Human RNome Project Consortium, led by Vivian Cheung, professor of molecular biology, cell biology and biochemistry, focused on unveiling the first ever complete draft of the human RNA genome.

The consortium began with a meeting at Brown around two and a half years ago. According to Cheung, there were “only 11 people in the room.” Since then, the consortium has grown to include researchers from 30 countries, all working together to sequence the body’s RNA.

Researchers such as Cheung have been working on The Human RNome Project Consortium as part of a “global effort to reveal the complete landscape of human RNA biology,” according to their website.

“The Human RNome Project began because we believed it was essential to measure this layer and create a reference for complete RNA molecules, including their sequences, isoforms, processing states and chemical modifications,” Charles Lee, associate dean of translational genomics and a professor of genetics and genome science at the University of Connecticut School of Medicine, wrote in an email to the Herald. Lee is also another founding member of the consortium.

The human body contains both DNA and RNA, and while every cell in one body has the same DNA, RNA mediates the differentiation of cells, according to Cheung.

“Our brain cells, our immune cells have the same DNA sequence, but clearly my brain cells are different from my immune cells,” said Cheung. “That’s mediated by the RNA, and yet we cannot read it.”

RNA is a key component of the flow of genetic information called the central dogma of molecular biology, acting as the bridge between DNA and protein. RNA is also involved in many other vital functions, such as gene regulation. The human RNome contains all of these RNA molecules.

The RNome also includes specific chemical modifications for more specific biological processes. According to Lee, “scientists have identified at least 50 different modifications in humans.”

At the early stages of this project, Cheung took a crowdsourcing approach; after making a huge batch of human RNA, the team sent samples to “anyone who had any kind of expertise in sequencing.”

“Whoever are the experts, if they come and ask us, we will send them a sample of RNA,” she said. “To our surprise, a lot of people asked, and we got back 180 (sequenced) samples from 15 countries.”

Then, using supercomputer technology from the U.S. Department of Energy, researchers uploaded the data to make the first RNA data hub, according to Cheung.

According to Lee, the RNome is much more “dynamic” compared to the genome. Because not one RNA sequencing technique captures the complete picture of the RNome, researchers engaged in various different methods to “produce reliable RNA maps that contain information on the modifications,” he wrote.

Peter Dedon, professor of biological engineering at the Massachusetts Institute of Technology and another founding member, emphasized that a big question during the data collection phase was how to standardize and store data collected from different methods.

“The tools for that don’t exist yet,” he added. “Part of this big project is to develop those tools.”

Cheung added that the next goal is for the data to be accepted for publication and made available to the public.

According to Robert Reenan, professor emeritus of molecular biology, cell biology and biochemistry who is not affiliated with the study, said that this RNA reference library would be “the dream” because it will allow researchers to get a more detailed picture of different types of RNA expression in different parts of the body.

“Maybe someone’s interested in bone development, brain development or lung disease. They can say, ‘Oh, well, these genes I know are expressed in the lung, and they go up in lung disease,’” Reenan explained.

Looking forward, Cheung hopes that Brown can become a hub for RNA biologists to look at the sequences of RNA and understand them.

“The Human RNome Project Consortium is not something that’s going to have a finite endpoint. It’s never going to end,” Dedon said.

Source – The Brown Daily Herald