https://www.seqanswers.com/ News about the latest advances and discoveries in sequencing and related technologies. en Wed, 01 Jul 2026 03:15:36 GMT vBulletin 60 https://www.seqanswers.com/images/misc/rss.png https://www.seqanswers.com/ https://www.seqanswers.com/forum/news/327402-new-ai-model-captures-long-range-genomic-signals-to-improve-rna-splice-site-prediction Tue, 30 Jun 2026 13:37:15 GMT A deep learning model developed at the University of Tokyo can analyze DNA sequences spanning up to 100,000 base pairs to predict RNA splice sites... A deep learning model developed at the University of Tokyo can analyze DNA sequences spanning up to 100,000 base pairs to predict RNA splice sites with single-nucleotide resolution—addressing a key limitation of existing computational tools that struggle to capture regulatory signals located far from the splice sites they influence. The study was published in Nucleic Acids Research.

Accurate RNA splicing is essential for gene expression and human health, yet predicting how DNA sequence variations affect splicing remains difficult. While recent AI models have improved splice site prediction, most cannot account for regulatory signals located thousands of base pairs away—limiting their ability to interpret disease-causing mutations in conditions ranging from genetic diseases to cancer.

To address this, Kenta Nakai and Yuna Miyachi developed SpliceSelectNet (SSNet), a hierarchical Transformer-based deep learning framework. A central challenge in modeling long-range genomic interactions is that computational cost increases rapidly with sequence length. SSNet addresses this by dividing long DNA sequences into smaller blocks, analyzing local patterns within each block, and then integrating information across the full sequence through a hierarchical attention process. This design preserves dense attention while remaining computationally efficient.

“The key achievement of this work is that we successfully modeled ultra-long-range genomic interactions while preserving high computational efficiency and single-nucleotide resolution,” said Professor Nakai. “We also demonstrated that the regions highlighted by the model closely correspond to biologically meaningful regulatory elements, helping to bridge predictive accuracy and biological interpretability.”

SSNet was trained and benchmarked against leading splice prediction systems across multiple large genomic datasets, achieving strong performance for both splice site prediction and aberrant splicing detection. In simulations using the DMD gene and evaluations of pathogenic variants from ClinVar, the model maintained sensitivity to regulatory signals located many thousands of base pairs from the affected splice site—beyond the effective range of conventional approaches.
“Many existing AI models for DNA analysis were adapted from natural language processing, but DNA has fundamentally different properties,” said Miyachi. “By redesigning the architecture to account for long-range genomic interactions and strict sequence resolution, we aimed to create a system better suited to biological reality.”

The researchers suggest the hierarchical Transformer architecture could support future work in promoter-enhancer interactions, three-dimensional genome organization, and broader DNA language models. In clinical settings, the approach could help screen variants in non-coding regions of uncertain significance, and in pharmaceutical research it could assist in designing oligonucleotide therapeutics that target abnormal splicing.
]]> News SEQadmin2 https://www.seqanswers.com/forum/news/327402-new-ai-model-captures-long-range-genomic-signals-to-improve-rna-splice-site-prediction https://www.seqanswers.com/forum/news/327396-large-scale-protein-screen-uncovers-hidden-regulators-of-alternative-polyadenylation Fri, 26 Jun 2026 19:10:46 GMT A team at the University of California San Diego has developed a large-scale screening approach that identifies proteins controlling alternative... A team at the University of California San Diego has developed a large-scale screening approach that identifies proteins controlling alternative polyadenylation (APA), a fundamental step in gene expression that occurs in more than 70% of human genes. The study was published in Molecular Cell.

APA determines where an RNA molecule is cut and finished before it is translated into protein, influencing the stability, localization, and function of thousands of genes. Abnormalities in APA have been implicated in cancer, neurological disorders, and other diseases, yet many of the proteins that regulate the process have remained unknown.

To address this gap, the research team screened 879 human RNA-binding proteins using a custom reporter system designed to measure how individual proteins influence APA. The screen identified 63 high-confidence activators of poly(A) site usage—the most important step of the APA process. Excluding known positive controls, only seven of these proteins had previously been associated with APA, meaning the vast majority represent newly identified regulators. Follow-up experiments confirmed that many of these proteins alter RNA processing in cells and affect distinct groups of genes involved in specific biological functions.

Among the most unexpected findings were new roles for two proteins, GRB2 and RNPS1, neither of which had previously been associated with APA. The study showed that both proteins can directly interact with components of the cellular machinery responsible for APA.

The researchers also trained a protein language model to predict APA regulators directly from protein sequences. The model successfully identified activators in an independent validation set and highlighted regions of proteins that appear critical for their function—an approach that could help accelerate the discovery of RNA regulatory proteins and provide insight into how they work.

Beyond cataloguing new regulators, the team developed a programmable RNA-targeting platform capable of recruiting specific proteins to particular poly(A) sites, creating a potential framework for manipulating RNA processing in a targeted manner. This could offer new possibilities for treating diseases linked to APA dysregulation.]]> News SEQadmin2 https://www.seqanswers.com/forum/news/327396-large-scale-protein-screen-uncovers-hidden-regulators-of-alternative-polyadenylation https://www.seqanswers.com/forum/news/327365-whole-genome-sequencing-traces-faroe-islands-ancestry-to-a-north-atlantic-founder-population Wed, 17 Jun 2026 14:09:33 GMT Whole-genome sequencing of 40 individuals from the Faroe Islands has shed new light on how this remote North Atlantic population descended from an... Whole-genome sequencing of 40 individuals from the Faroe Islands has shed new light on how this remote North Atlantic population descended from an ancient founder group and how evolutionary forces have shaped their genomes over time. The findings, published in eLife, offer insights into the genetic underpinnings of diseases that occur at elevated rates on the islands, including type 2 diabetes and multiple sclerosis.

The Faroe Islands sit between Iceland and Norway and are home to descendants of a founder population whose settlement history remains only partially understood. Records suggest a small number of founders arrived from Scandinavia and the British Isles around the 9th century CE, though archaeological evidence points to potentially earlier habitation. All sequencing for the study was conducted locally, in the FarGen laboratory on the Faroe Islands, as part of the Faroe Genome (FarGen) project.

"No population genomic studies of this scale have yet been carried out on whole-genome sequencing data from Faroese individuals to date. An in-depth analysis of individuals' genomic architecture may reveal how the islands' demographic history has contributed to present-day health and disease in the population and may shed light on why there's a high prevalence of certain diseases such as type 2 diabetes and multiple sclerosis," said Iman Hamid, co-first author of the study.

A key finding involved runs of homozygosity—continuous stretches of identical genotypes inherited from both parents. Faroese individuals carry a higher proportion of long runs of homozygosity than even Finnish individuals, a well-studied founder population, suggesting a more recent or stronger evolutionary bottleneck in Faroese history and a significant reduction in genetic diversity at some point in the past.

Sequencing data also identified genes that underwent positive selection in the Faroese population. Many overlapped with the British population, reflecting shared ancestry, but several were unique. These included the lactase persistence gene, potentially tied to the later introduction of dairy into the traditional diet, along with POLQ, involved in DNA repair and cancer, and SLC10A1, which plays a role in vitamin D absorption—relevant given the islands' northern latitude and limited UV exposure.
Ancestry analysis comparing Faroese genomes against European datasets spanning 3,000 years suggests the present-day population descended from already-admixed founders of both Northern and Western European ancestry.

"Our study highlights the impact of evolutionary processes, such as ancient admixture and positive selection, on the present-day genetic make-up of the Faroese population. Future studies should combine genomic data with physical traits to provide insights into the genetic mechanisms underlying those traits, especially those involved in autoimmune and metabolic disease on the Islands," said Noomi Gregersen, corresponding author of the study.

]]> News SEQadmin2 https://www.seqanswers.com/forum/news/327365-whole-genome-sequencing-traces-faroe-islands-ancestry-to-a-north-atlantic-founder-population https://www.seqanswers.com/forum/news/327363-sequencing-the-two-toed-sloth-genome-reveals-jumping-genes-tied-to-its-extreme-metabolism Tue, 09 Jun 2026 19:58:52 GMT Sloths are the slowest mammals on Earth, and their dense jungle habitat has made them notoriously difficult to study. Now, for the first time,... Sloths are the slowest mammals on Earth, and their dense jungle habitat has made them notoriously difficult to study. Now, for the first time, scientists have sequenced and analyzed the two-toed sloth genome, uncovering the genetics behind their exceptionally slow metabolism. The results were published in BMC Biology.

The work was led by researchers at the Wellcome Sanger Institute, the Leibniz Institute for Zoo and Wildlife Research (IZW), and Hospital Sírio Libanês, building on work initiated at IZW. Using DNA extracted from the tissues of a captive two-toed sloth—sequenced at the Max-Planck Institute for Molecular Cell Biology & Genetics—the team compared the sloth genome to those of related mammals, including anteaters and armadillos, through comparative genomics.

Sloths belong to Xenarthra, the only clade of placental mammals to have originated in South America, a group that has existed for 65.5 million years. Modern sloths spend most of their time hanging motionless in trees, feeding on leaves and fruit at a slow pace. Their metabolism is often less than half of what would be expected for their body size, and to conserve energy they can switch between regulating their own body temperature and allowing it to fluctuate with the environment.

The scientists found that the sloth genome contains several copies of active transposable elements—known as transposons or "jumping genes"—DNA sequences that can copy and paste themselves to new positions in the genome. In humans, transposons are typically inactive, old, and fragmented; active ones can cause chromosomal rearrangements linked to cancer. In sloths, these elements are still active and have been conserved since arising in the last common ancestor of all surviving sloth species approximately 30 million years ago.

Notably, many of these genes are connected to mitochondria and to metabolic pathways. The researchers believe these sloth-specific genes are related to the evolution of the animal's unusual metabolism.

“Evolution has already run billions of experiments,” said Marcela Uliano-Silva, co-lead author of the study. “By studying unusual animals like sloths, we sometimes uncover biological solutions that humans never evolved. Using genomics to look back through time, we found ‘jumping genes’ that sloths have conserved over millions of years. These sloth-specific genes are linked to mitochondria and metabolic pathways, suggesting they might be related to the evolution of their extremely slow metabolism.”

The team's next step is to study these genes in cell lines using lab experiments and single-cell sequencing to validate their function. Sloth cell lines, the researchers suggest, may offer a useful model for studying metabolism-associated and age-related conditions in mammals.

“Many human conditions—including diabetes, ageing-related disorders, neurodegeneration, and muscle wasting—involve problems with energy production and mitochondrial function,” said co-lead Pedro Galante. “In the long term, this could inform research into tissue preservation, critical care medicine, ageing, metabolic disease, and even long-duration space travel.”
]]> News SEQadmin2 https://www.seqanswers.com/forum/news/327363-sequencing-the-two-toed-sloth-genome-reveals-jumping-genes-tied-to-its-extreme-metabolism https://www.seqanswers.com/forum/news/327360-a-new-method-makes-hantavirus-genome-analysis-faster-and-more-accessible Fri, 05 Jun 2026 18:09:02 GMT Hantavirus infections are rare—roughly 30 people are infected in the United States each year—but they are deadly, killing 30 to 40 percent of those... Hantavirus infections are rare—roughly 30 people are infected in the United States each year—but they are deadly, killing 30 to 40 percent of those infected. Most U.S. cases are caused by Sin Nombre virus, carried by the deer mouse. When cases occur, public health officials need rapid, detailed genomic information to identify the strain, trace its origin, and prevent further exposure. A new method for whole-genome sequencing of hantaviruses, introduced at ASM Microbe 2026, offers a more effective and lower-cost approach to that challenge.

The method was developed by Janet Manson from the California Department of Public Health. Sequencing hantavirus genomes has historically been difficult due to the virus’s complex genome structure, high genetic diversity, and the low viral concentrations typically found in human specimens—factors that have left few whole genome sequences publicly available.

To overcome these obstacles, Manson and her colleagues designed a primer capable of recognizing and attaching to the hantavirus genome during conversion of viral RNA into DNA, then developed a method to sequence each genome segment in one long piece. For samples with low viral concentration, a second step was added to increase genome yield, making it possible to successfully sequence samples that would otherwise contain too little viral material to analyze.

In lab testing, the approach generated whole genome sequencing data from 35 rodent samples that had previously tested positive for Sin Nombre virus. It has also proven useful in real-world public health work. In one recent case, Manson was able to match the genome sequence from an infected person to that of a rodent caught near the person's home—the kind of information that helps confirm where exposures occur and directs public health interventions to where they are most needed.

"When there's an outbreak or even a case, we need to know where that person was exposed so we can stop other people from being exposed," Manson explained.

Beyond its scientific utility, the method is designed to be accessible. The sequencing device can be plugged into a laptop and costs approximately $3,000—comparatively cheap to set up relative to other common technologies. Manson hopes the tool will be adopted by other states, many of which lack resources to maintain whole genome sequencing capacity for rarer viruses.

The team is now expanding the method to other hantaviruses beyond Sin Nombre, recently sequencing the genome of a virus similar to Andes virus from a person who had traveled to Paraguay. "We really want to better understand the diversity of hantaviruses across the U.S., and we want to be able to look at markers of viral evolution, just to understand what's happening," Manson said.
]]> News SEQadmin2 https://www.seqanswers.com/forum/news/327360-a-new-method-makes-hantavirus-genome-analysis-faster-and-more-accessible https://www.seqanswers.com/forum/news/327357-a-new-single-cell-method-maps-dna-protein-interactions Thu, 04 Jun 2026 16:59:23 GMT Scientists at Weill Cornell Medicine and the New York Genome Center have developed a new method that maps, in single cells, the DNA binding sites of... Scientists at Weill Cornell Medicine and the New York Genome Center have developed a new method that maps, in single cells, the DNA binding sites of transcription factors and other regulatory proteins that control gene activity. The technique, called D&D-seq, addresses significant drawbacks of existing tools and is the first of its kind that can be readily incorporated into high-throughput, single-cell multi-omics workflows. The study was published in Cell.

Transcription factors and other DNA-binding proteins play a critical role in switching genes on and off, and a large proportion of disease-risk hotspots identified in genetics studies lie at transcription factor binding sites. Despite their importance, tools for mapping actual transcription factor binding events in cells have had notable limitations—including insensitivity to weak or transient binding events and incompatibility with standard multi-omics platforms, making it difficult to get a complete picture of how genes and gene networks are regulated.

D&D-seq— short for docking and deaminase sequencing—works by using antibodies to bring a DNA-editing enzyme close to a target protein. Even a brief interaction between the deaminase-linked protein and DNA leaves a detectable mark in sequencing data. "DNA is a marvelous molecule for recording and storing information, and we are exploiting this property to our advantage," said Ivan Raimondi, co-senior author on the study.

The team demonstrated D&D-seq by mapping binding sites of several transcription factors and chromatin remodeling proteins—proteins that influence gene activity by opening or closing the local structure of DNA. One demonstration mapped the binding sites of a key transcription factor in blood cells, comparing cells with and without a common leukemia mutation, revealing in detail how the mutation alters transcription factor binding.

Critically, D&D-seq is compatible with existing single-cell multi-omics platforms, allowing protein-DNA interaction data to be collected alongside gene activity patterns, genome sequences, and other omics layers in the same experiment. "D&D-seq is platform-agnostic—it's basically a plug-and-play feature that you can add to existing platforms to get more information from your experiments," Dr. Raimondi said.

"A lot of research has been held back because we didn't have the right tools for mapping DNA-protein interactions in single cells; and now that we have such a tool there is enormous excitement—it's really a foundational technological advance," said co-senior author Dan Landau.]]> News SEQadmin2 https://www.seqanswers.com/forum/news/327357-a-new-single-cell-method-maps-dna-protein-interactions https://www.seqanswers.com/forum/news/327353-long-read-rna-sequencing-uncovers-a-hidden-layer-of-immune-cell-regulation Tue, 02 Jun 2026 20:03:07 GMT Scientists at University Medical Center Utrecht have identified a previously underappreciated mechanism that helps immune cells respond rapidly to... Scientists at University Medical Center Utrecht have identified a previously underappreciated mechanism that helps immune cells respond rapidly to infection. Using long-read RNA sequencing, the team demonstrates that alternative RNA splicing plays a central role in shaping immune responses. The findings, published in Nature Communications, may open the door to more targeted therapies for immune-mediated diseases including rheumatoid arthritis and lupus.

The study focused on monocytes, innate immune cells that act as first responders to pathogens. While previous research has largely examined changes in overall gene expression, this study focused on RNA isoforms—the different transcript variants a single gene can produce. The team generated a comprehensive map of full-length RNA transcripts in human monocytes before and after activation with bacterial components, identifying more than 24,000 isoforms, the majority of which have never been described.

A key finding is that immune activation triggers widespread isoform switching. Rather than simply turning genes on or off, monocytes shift toward producing longer, fully functional RNA variants more likely to be translated into proteins. These isoforms contain complete coding sequences, fewer non-coding interruptions, and greater structural complexity—features associated with more effective protein production.

"In our study we also confirmed that these RNA changes have real functional consequences. By integrating data on protein synthesis and ribosome activity, we demonstrated that the observed isoform shifts are linked to increased production of immune effector proteins. This shows that alternative splicing directly enhances the cell's ability to respond to infection or inflammation," Jorg van Loosdregt Ph.D., principal investigator of the study.

The findings carry implications for immune-mediated diseases such as rheumatoid arthritis and lupus, conditions previously linked to genetic variation affecting RNA splicing. The study adds a new layer of insight, suggesting that disease mechanisms may depend not only on which genes are expressed, but on which isoforms are produced and how efficiently they are translated into proteins.

Van Loosdregt noted that traditional methods may overlook critical changes that only become visible with full-length RNA analysis, and that the adoption of long-read sequencing technologies could transform research into immune function and disease mechanisms.

Co-author Bas Vastert added: "For patients with an immune-mediated disease, the findings point toward new therapeutic opportunities. If harmful immune responses are driven by specific splicing patterns, these processes could potentially be targeted. Emerging approaches, such as antisense oligonucleotides or drugs that influence splicing factors, may enable more precise modulation of the immune system and the development of targeted treatments for immune-mediated diseases in the future."
]]> News SEQadmin2 https://www.seqanswers.com/forum/news/327353-long-read-rna-sequencing-uncovers-a-hidden-layer-of-immune-cell-regulation https://www.seqanswers.com/forum/news/327352-dna-methylation-study-reveals-how-epigenetic-changes-pass-between-generations Tue, 02 Jun 2026 19:40:10 GMT DNA methylation is one of the most studied epigenetic modifications, yet its ancestral function in animals and its capacity for transgenerational... DNA methylation is one of the most studied epigenetic modifications, yet its ancestral function in animals and its capacity for transgenerational inheritance remain incompletely understood. While mammals undergo extensive epigenetic reprogramming after fertilization—largely preventing the transmission of acquired methylation states across generations—this resetting mechanism appears to be absent in invertebrates, raising questions about how methylation patterns are maintained and what consequences arise when they are disrupted.

To explore what happens when epigenetic patterns are disrupted, scientists from Queen Mary University experimentally removed DNA methylation in the sea anemone Nematostella vectensis. The results were unexpected: animals developed normally despite losing most of their DNA methylation. Rather than causing major defects in gene regulation, the loss of methylation mainly unleashed hidden "jumping genes"—also called "selfish genes"—embedded within active genes. Left unchecked, these genetic parasites can insert themselves into important genes and regulatory regions, potentially disrupting normal development and threatening genome stability.

The study also revealed that because sea anemones lack the extensive epigenetic resetting that occurs after fertilization in mammals, some abnormal methylation states persisted in offspring. "These inherited epigenetic changes altered how genes are switched on in the next generation, demonstrating that experimentally induced epigenetic variation can be transmitted across generations in an animal," said Alex de Mendoza, senior author of the study published in Nature Ecology & Evolution.

The findings suggest that the ancestral role of DNA methylation in animals was not primarily to regulate gene expression, but to protect active genes from disruptive jumping genes. In mammals, this same molecular system has since taken on a broader range of functions, including regulating development and silencing one of the two X chromosomes in females.

The work also shows how incomplete epigenetic resetting can allow heritable variation to persist across generations without requiring any changes to the genetic code itself—potentially providing raw material for evolutionary change. In doing so, the study offers a window into the evolutionary origins of important regulatory systems, and demonstrates how more ancient mechanisms of gene regulation can transmit information through generations.
]]> News SEQadmin2 https://www.seqanswers.com/forum/news/327352-dna-methylation-study-reveals-how-epigenetic-changes-pass-between-generations