Journal News

Improvements in human genome databases offer a promising future for cancer research

Scientists expand the use of ribosome profiling, also known as Ribo-seq, to understand protein production in cells
Patricia DeLacey Tessa Roy
By Patricia DeLacey and Tessa Roy
Oct. 1, 2023

A gene sequencing method called ribosome profiling has expanded our understanding of the human genome by identifying previously unknown protein coding regions. Also known as Ribo-seq, this method allows researchers to get a high-resolution snapshot of protein production in cells.

Ribo-seq has the potential to advance cancer research, but many of the discoveries enabled by Ribo-seq provide an untraditional view of where and how protein production might happen. As such, scientists must first verify these regions code for proteins.

A tool for cancer research

“Ribo-seq has garnered major interest for use in studying protein production in cancer cells to identify a specific abnormal proteins as targets for immunotherapy or other treatment approaches,” said John Prensner, a physician-researcher and assistant professor in the University of Michigan Medical School Departments of Pediatrics and Biological Chemistry.

Immunotherapy treatment activates the patient’s own immune system to destroy cancer cells. It lacks the toxic side effects of chemotherapy like nausea, vomiting and hair loss, making it a highly desirable treatment for patients that qualify.

Currently, immunotherapy is only available for certain cancers. Tumors that produce a large number of proteins with easily identifiable mutations are compatible with immunotherapy. Drugs have been developed to target those proteins to unleash the immune system against cancerous cells.

Scientists hope to use Ribo-seq as a tool to understand the proteins cancer cells produce to expand immunotherapy’s success to a larger number of cancer patients.

Investigating protein machines

Producing a protein requires two steps — transcription and translation. Ribo-seq zeroes in on the second step of translation.

During transcription, the cell takes the DNA master blueprint and makes a copy of the genetic instructions known as messenger RNA or mRNA. The messenger RNA is then shuttled over to a ribosome, a tiny protein factory within the cell, to start the process of translation. The ribosome translates the instructions to link amino acids together to form a protein.

In the past, researchers have used RNA sequencing or RNA-seq to identify genes that are activated to make proteins in a given tissue sample, Prensner said. For example, RNA-seq could be used to identify which genes a cancer cell is using to make proteins and identify any mutations in those proteins.

RNA-seq is a proxy for the process of translation, but there are multiple factors that can alter results. Ribo-seq analyzes the translation process, giving a clearer picture of the rate and location of translation.

Collaboration to improve databases

When scientists first get back the results of any genetic sequencing, to make any sense of the long list of letters, they must align the genetic sequence to a reference genome. Reference genomes are a digital database of an accepted representation of an organism’s gene sequence.

If a scientist is studying cancer biology in the human genome, they would use a human genome reference sequence as a standard comparison to the gene sequence generated in their study to learn more about function. Currently, human genome reference databases are not well equipped to recognize Ribo-seq results. The lack of standardization inhibits Ribo-seq’s use for the global research community.

To remedy this, Prensner, whose lab focuses on the molecular basis of pediatric brain cancers, teamed up with an international group of researchers to begin a project to improve human genome reference databases for Ribo-Seq use.

During Phase I of the project, this team of research organizations  produced a standardized catalog of 7,264 Ribo-seq open reading frames — spans of DNA fragments that code for proteins — which is made freely available to scientists worldwide. Although a good start, this catalog requires additional scrutiny to answer a critical question for the research community: How many of these open reading frames truly produce a protein product?

Cross-checking results

Prensner led a research effort to integrate Ribo-Seq and proteomics techniques, laboratory methods to confirm the presence of a protein within a cell, to increase researchers’ confidence in whether these Ribo-Seq open reading frames produce proteins. The results are published in Molecular & Cellular Proteomics. The research team proposes a framework to standardize levels of evidence for these newly identified protein-coding regions.

Classifications vary from “protein candidate” with the strongest required supporting evidence to “detected” with the least required supporting evidence.

“We believe this common terminology and shared database resources will reduce confusion and improve the precision of research on these open reading frames identified by Ribo-Seq,” Prensner said.

Improved databases will support more accurate gene sequencing interpretations and foster insights in cancer as well as across all aspects of human biology for years to come.

This article was first published by Health Lab, Michigan Medicine’s daily online publication. Read the original.

Enjoy reading ASBMB Today?

Become a member to receive the print edition monthly and the digital edition weekly.

Learn more
Patricia DeLacey
Patricia DeLacey

Patricia DeLacey is a contributing writer for Health Lab, Michigan Medicine’s daily online publication. She is passionate about sharing cutting-edge research with the public. Her doctoral work conducted at the University of Michigan focused on chest color in wild male gelada monkeys, a sexually selected trait used in male competition. She leverages her research experience to communicate science and health stories to a general audience.

Tessa Roy
Tessa Roy

Tessa Roy handles communications for several departments across Michigan Medicine, including Kellogg Eye Center, nephrology, Survival Flight/emergency medicine, diabetes/endocrinology, allergy/dermatology, and women’s and children’s. She was previously a journalist and a state government staffer in Rhode Island and Michigan.

Related articles

Seeking leukemia’s Achilles heel
Marissa Locke Rottinghaus
From the journals: March 2019
John Arnst, Courtney Chandler, Isha Dey & Catherine Goodman
Finding a way to combat long COVID
Marissa Locke Rottinghaus

Get the latest from ASBMB Today

Enter your email address, and we’ll send you a weekly email with recent articles, interviews and more.

Latest in Science

Science highlights or most popular articles

Weedy rice gets competitive boost from its wild neighbors
News

Weedy rice gets competitive boost from its wild neighbors

May 18, 2024

Rice feeds the world. But researchers have found that a look-alike weed has many ways of getting ahead.

From the journals: JLR
Journal News

From the journals: JLR

May 17, 2024

A “T” makes a difference in blood clotting. High cholesterol: two screens are better than one. Biomarkers for cardiovascular risk. Statin-induced changes to the HDL lipidome. Read about recent papers on these topics.

Decoding microglial language
Journal News

Decoding microglial language

May 14, 2024

Emory University scientists characterize extracellular vesicles that facilitate intercellular communication.

What is metabolism?
News

What is metabolism?

May 12, 2024

A biochemist explains how different people convert energy differently – and why that matters for your health.

What’s next in the Ozempic era?
News

What’s next in the Ozempic era?

May 11, 2024

Diabetes, weight loss and now heart health: A new family of drugs is changing the way scientists are thinking about obesity — and more uses are on the horizon.

How a gene spurs tooth development
Journal News

How a gene spurs tooth development

May 7, 2024

University of Iowa researchers find a clue in a rare genetic disorder’s missing chromosome.