Weill Cornell Medicine and New York Genome Center researchers, in collaboration with Oxford Nanopore Technologies, have developed a new method to assess on a large scale the three-dimensional structure of the human genome, or how the genome folds. The genome is the complete set of genetic instructions, DNA or RNA, enabling an organism to function. | |
Using this method, the researchers demonstrated that cell function, including gene expression, may be affected by groups of simultaneously interacting regulatory elements in the genome rather than pairs of these components. Their findings, published in Nature Biotechnology (“Team architecture in 3D genomic interactions revealed through nanopore sequencing”), may help shed light on the relationship between genome structure and cellular identity. | |
“Knowing the three-dimensional genome structure will help researchers better understand how the genome functions, and particularly how it encodes different cell identities,” said senior author Dr. Marcin Imieliński, associate professor of pathology and laboratory medicine and computational genomics in computational biomedicine at Weill Cornell Medicine and a core member of the New York Genome Center. “The ways that we’ve had to study genome structure have given us amazing insights, but there have also been key limitations,” he said. | |
For example, previous technology to assess the genome’s three-dimensional structure has allowed researchers to study how frequently two loci, or physical locations on the genome, interact with one another. Traditionally, pairs of loci called enhancers and promoters – components in the genome that interact with one another to influence gene expression – have been observed. | |
Information about these pairings offers incomplete insight into genome structure and function. For instance, linking a folding pattern to how the genome encodes for a specific cell identity – like a liver, lung or epithelial cell – has been difficult, said Imieliński, who is also a member of the Englander Institute for Precision Medicine and the Sandra and Edward Meyer Cancer Center at Weill Cornell Medicine. Scientists have theorized that this folding influences gene expression. “But how cell types are encoded, particularly in the structure of DNA, has been a mystery,” he said. | |
Imieliński and his research team, including first author Aditya Deshpande, a recent graduate of the Tri-Institutional Ph.D. Program in Computational Biology & Medicine working in Imieliński’s lab, developed a new genome-wide assay and algorithm that allows them to study groups of loci, not just pairs. | |
They adapted a traditional technology, Hi-C (chromatin conformation capture), which assesses a mixture of DNA and protein to analyze three-dimensional genome structure, to nanopore sequencing, or the high-throughput sequencing of long, continuous strands of DNA molecules. The resulting assay, which the researchers called Pore-C, enabled them to observe tens of millions of three-dimensional locus groupings. | |
They also developed statistical methods to determine which locus groupings were important, based on whether they interacted cooperatively to affect gene expression. “Many three-dimensional interactions of the genome are not important,” Imieliński said. “Our analytic methods help us prioritize the group interactions that are likely to matter for genome function.” As a key finding of the study, the researchers found that the most significant cooperative groupings of DNA elements occurred around genes associated with cell identity. | |
Future experiments will explore which specific groupings of genomic components are essential for various aspects of cell identity. The new technology may also help researchers to understand how stem cells, the immature, master cells of the body, differentiate into different cell types. | |
In addition, researchers may be better able understand abnormalities in cancer cells. “In the future, this technology may be really helpful in understanding how cancer cell genomes are rearranged, and how those rearrangements drive the altered cell identities that enable cancers to grow and spread” Imieliński said. |

News
A potential milestone in cancer therapy
Researchers from the University of Bern, Inselspital, University Hospital Bern, and the University of Connecticut have made a significant breakthrough in the fight against cancer. They identified a previously unknown weak point of prostate [...]
Cardiovascular Crystal Ball: New Tool Predicts Future Heart Disease Risk
Faculty members at the UM School of Medicine have created a cutting-edge tool that enables the early identification and assessment of risks in vulnerable patients. Heart disease, being the leading cause of death globally, [...]
Scientists analyze a single atom with X-rays for the first time
In the most powerful X-ray facilities in the world, scientists can analyze samples so small they contain only 10,000 atoms. Smaller sizes have proved exceedingly difficult to achieve, but a multi-institutional team has scaled [...]
AI Demonstrates Superior Performance in Predicting Breast Cancer
AI algorithms outperformed traditional clinical risk models in a large-scale study, predicting five-year breast cancer risk more accurately. These models use mammograms as the single data source, offering potential advantages in individualizing patient care [...]
Stanford Medicine Reveals: Tiny DNA Circles Defying Genetic Laws Drive Cancer Formation
Tiny circles of DNA harbor cancer-associated oncogenes and immunomodulatory genes promoting cancer development. They arise during the transformation from pre-cancer to cancer, say Stanford Medicine-led team. Tiny circles of DNA that defy the accepted laws of [...]
Death to Blood Cancer Cells: New Drug Combination Could Revive the Power of Leading Treatment
Future clinical trials will be conducted to investigate whether the combination of chloroquine and venetoclax can prevent disease recurrence. Although new drugs have been developed to induce cancer cell death in individuals with acute [...]
Illuminating Science: X-Rays Visualize How One of Nature’s Strongest Bonds Breaks
Scientists have deciphered how an activated catalyst breaks down the strong carbon-hydrogen bonds in potent greenhouse gas methane, according to a study published in Science. Using advanced X-ray technology and quantum-chemical calculations, they tracked the [...]
Using magnetic nanoparticles as a rapid test for sepsis
Qun Ren, an Empa researcher, and her team are currently developing a diagnostic procedure that can rapidly detect life-threatening blood poisoning caused by staphylococcus bacteria. Staphylococcal sepsis is fatal in up to 40% of [...]
Team develops nanoparticles to deliver brain cancer treatment
University of Queensland researchers have developed a nanoparticle to take a chemotherapy drug into fast growing, aggressive brain tumors. Research team lead Dr. Taskeen Janjua from UQ's School of Pharmacy said the new silica [...]
Tumor Avatars – A New Approach to Personalized Cancer Treatment
A team from the University of Geneva (UNIGE) has devised a novel method for customizing treatments by testing them on artificial tumors. Determining the optimal treatment for colon cancer can be challenging as each [...]
STING Like a Bee: MIT’s Revolutionary Approach to Cancer Immunotherapy
A cancer vaccine combining checkpoint blockade therapy and a STING-activating drug eliminates tumors and prevents recurrence in mice. MIT researchers have engineered a therapeutic cancer vaccine that targets the STING pathway, vital for immune response [...]
AI Battles Superbugs: Helps Find New Antibiotic Drug To Combat Drug-Resistant Infections
The machine-learning algorithm identified a compound that kills Acinetobacter baumannii, a bacterium that lurks in many hospital settings. Using an artificial intelligence algorithm, researchers at MIT and McMaster University have identified a new antibiotic that can kill a [...]
Cancer and AI – Can ChatGPT Be Trusted?
A study published in the Journal of The National Cancer Institute Cancer Spectrum delved into the increasing use of chatbots and artificial intelligence (AI) in providing cancer-related information. The researchers discovered that these digital resources accurately [...]
Breathing New Life: Oxygen Therapy Improves Heart Function in Long COVID Patients
A small trial has found that hyperbaric oxygen therapy (HBOT) may help restore proper heart function in patients with post-COVID syndrome, with participants in the HBOT group experiencing a significant increase in global longitudinal [...]
Wireless Brain-Spine Interface: A Leap Towards Reversing Paralysis
Summary: In a pioneering study, researchers designed a wireless brain-spine interface enabling a paralyzed man to walk naturally again. The ‘digital bridge’ comprises two electronic implants — one on the brain and another on the [...]
New study reveals a gel that promises to wipe out brain cancer for good
An anti-cancer gel promises to wipe out glioblastoma permanently, a feat that's never been accomplished by any drug or surgery. So what makes this gel so special? Scientists at Johns Hopkins University (JHU) have [...]