HSE Researchers Create Genome-Wide Map of Quadruplexes
An international team, including researchers from HSE University, has created the first comprehensive map of quadruplexes—unstable DNA structures involved in gene regulation. For the first time, scientists have shown that these structures function in pairs: one is located in a DNA region that initiates gene transcription, while the other lies in a nearby region that enhances this process. In healthy tissues, quadruplexes regulate tissue-specific genes, whereas in cancerous tissues they influence genes responsible for cell growth and division. These findings may contribute to the development of new anticancer drugs that target quadruplexes. The study has been published in Nucleic Acids Research.
The word 'DNA' usually brings to mind a double helix, but this molecule can adopt other forms as well. In some regions, the DNA strand can unwind, bend, and form a small knot. If such a fragment is rich in guanine (denoted by the letter G in the DNA sequence), it can fold into a quadruplex—a three-dimensional structure in which several layers of guanine are stacked on top of one another. For proteins that regulate gene activity, these structures serve as prominent landmarks, helping them locate the correct regions of DNA.
Quadruplexes are short-lived structures: they form rapidly, perform their function, and then disappear, meaning that experiments can capture only a fraction of them. Moreover, different experimental methods detect different types of quadruplexes. As a result, it has not been possible to create a genome-wide map that includes all DNA regions where quadruplexes can form.
To address this problem, the team of HSE researchers further trained the genomic language model DNABERT on quadruplex data and used its predictions to reconstruct where these structures arise across the genome.
Maria Poptsova
'In our study, we trained DNABERT on EndoQuad, the world’s largest database of experimentally validated quadruplexes, resulting in the GQ-DNABERT model. This model evaluates DNA sequences to predict where a quadruplex is likely to form,' comments Maria Poptsova, Director of the Centre for Biomedical Research and Technology at the HSE Faculty of Computer Science.
Unlike simple algorithms that search only for sequences capable of forming a quadruplex, GQ-DNABERT also considers the surrounding DNA context, which determines whether a region actually folds into a quadruplex. As a result, the model was able to predict about 360,000 quadruplexes—far more than have been identified by individual experimental methods.
The model confirmed the well-known fact that quadruplexes frequently occur in promoters—DNA regions upstream of genes where transcription is initiated. Unexpectedly, many quadruplexes were also found in nearby enhancers, genomic elements that boost gene transcription and influence how much protein is produced. The researchers discovered that quadruplexes often form simultaneously in both the promoter and the enhancer, creating pairs that jointly regulate gene activity.
To investigate the role of these pairs in cells, the researchers used single-cell sequencing data from experiments. In such datasets, the DNA regions that are statistically associated with the activity of specific genes are pre-identified. By overlaying the GQ-DNABERT map for six tissue types onto these data, the scientists found that promoter–enhancer pairs are more often associated with genes responsible for tissue-specific functions: in the brain, for neuronal development and function; in the blood, for immune cell activity; and in the intestine, for epithelial functions. The researchers then examined these pairs in tumour tissues and compared them with those in healthy tissues. While the number of promoter–enhancer pairs containing quadruplexes was similar, the functions of the associated genes differed dramatically.
'In normal cells, these pairs are associated with tissue-specific programmes, whereas in cancer cells they are linked to universal processes of cell division and growth that drive tumour proliferation regardless of the tissue of origin,' explains Poptsova. 'In other words, in healthy cells, these pairs support tissue specialisation, while in cancer they become part of general programmes for rapid cell division.'
The resulting map of quadruplexes provides a clearer understanding of how these structures regulate gene activity in both normal and tumour cells. In the future, this information could be used to develop new anticancer drugs that selectively target quadruplexes.
The study was supported by a grant from the HSE AI Research Centre.
See also:
Immersion in Second Language Environment Influences Bilinguals’ Perception of Emotions
Researchers at the Cognitive Health and Intelligence Centre at the HSE Institute for Cognitive Neuroscience have discovered how bilingual individuals process emotional words in their native (first) and non-native (second) languages. It was found that the link between word meaning and bodily sensations is weaker in a second language than in a first language. However, the more a person is immersed in a language environment, the smaller this difference becomes. The article has been published in Language, Cognition and Neuroscience.
HSE Students Among Winners of Yandex High-Tech Startup Accelerator
Yandex has announced the results of its Yandex AI Startup Lab accelerator, whose final round featured 12 IT projects. Over the course of three months, their creators—students and young entrepreneurs—worked alongside the company’s experts to develop their products. Four startups in digital marketing, medicine, and robotics were named the best, with their teams receiving cash prizes and cloud resource grants. Among them was Gradius, a startup founded by students from HSE University.
Researchers Find More Effective Approach to Revealing Majorana Zero Modes in Superconductors
An international team of researchers, including physicists from HSE MIEM, has demonstrated that nonmagnetic impurities can help more accurately reveal Majorana zero modes—quantum states considered promising building blocks for quantum computing. The researchers found that these impurities shift the energy levels that typically obscure the Majorana signal, while leaving the mode itself largely unaffected, thereby making its spectral peak more distinct. The study has been published in Research.
New Development by HSE Scientists Helps Design Reliable Electronics Faster at a Lower Cost
Scientists from HSE MIEM have developed a new approach to modelling electrothermal processes in high-power electronic circuits on printed circuit boards (PCB). The method allows engineers to quickly and accurately predict how electronic components heat up during operation, helping prevent overheating and potential failures. The results have been published in Russian Microelectronics.
The Future of Cardiogenetics Lies in Artificial Intelligence
Researchers from the AI and Digital Science Institute at the HSE Faculty of Computer Science have developed a program capable of analysing regions of the human genome that were previously inaccessible for accurate interpretation in genetic testing. The program adapts large generative AI (GenAI) models for cardiogenetics to predict how specific mutations affect the function of individual genes.
HSE Researchers: Young Russians Have Sufficient Knowledge About Money but Lack Money Management Skills
Adolescents and young adults in Russia today are well versed in financial terminology: they know what bank cards, loans, interest rates, and online payments are. However, as researchers at HSE University have found, real money-management skills remain poorly developed among most young people. The study ‘Financial Literacy, Financial Culture, and Financial Autonomy of Youth’ has been published in Monitoring of Public Opinion: Economic and Social Changes.
Why Weaker Competitors Give Up—and How to Keep Them in the Game
Anastasia Antsygina, Assistant Professor at HSE University’s Faculty of Economic Sciences, has developed a prize distribution model that maximises competitor engagement. She proposed revising the traditional ‘winner-takes-all’ approach and, in certain cases, offering a small reward even to those who have lost. According to her, this could increase participant motivation and make the competition more intense. The findings of her research were published in the Economic Theory journal.
HSE Researchers Compile Scientific Database for Studying Children’s Eating Habits
The database created at HSE University can serve as a foundation for studying children’s eating habits. This is outlined in the study ‘The Influence of Age, Gender, and Social-Role Factors on Children’s Compliance with Age-Based Nutritional Norms: An Experimental Study Using the Dish-I-Wish Web Application.’ The work has been carried out as part of the HSE Basic Research Programme and was presented at the XXVI April International Academic Conference named after Evgeny Yasin.
New Foresight Centre Study Identifies the Most Destructive Global Trends for Humankind
A team of researchers from the HSE International Research and Educational Foresight Centre has examined how global trends affect the quality of human life—from life expectancy to professional fulfilment. The findings of the study titled ‘Human Capital Transformation under the Influence of Global Trends’ were published in Foresight.
Scientists Develop Algorithm for Accurate Financial Time Series Forecasting
Researchers at the HSE Faculty of Computer Science benchmarked more than 200,000 model configurations for predicting financial asset prices and realised volatility, showing that performance can be improved by filtering out noise at specific frequencies in advance. This technique increased accuracy in 65% of cases. The authors also developed their own algorithm, which achieves accuracy comparable to that of the best models while requiring less computational power. The study has been published in Applied Soft Computing.