https://www.seqanswers.com/ News about the latest advances and discoveries in sequencing and related technologies. en Sat, 24 Oct 2026 01:26:19 GMT vBulletin 60 https://www.seqanswers.com/images/misc/rss.png https://www.seqanswers.com/ https://www.seqanswers.com/forum/news/327719-exeter-led-study-maps-what-an-average-human-genome-looks-like Thu, 22 Oct 2026 19:13:38 GMT A new study from the University of Exeter has characterized what counts as an “average” human genome, offering a reference point for normal genetic... A new study from the University of Exeter has characterized what counts as an “average” human genome, offering a reference point for normal genetic variation and genetic disease risk. Published in Genome Medicine, the research drew on nearly one million whole genome sequences from two major population biobanks, UK Biobank and the U.S.-based All of Us program, funded by the Medical Research Council, Wellcome and the NIHR Biomedical Research Centre: Exeter.

The analysis points to an uncomfortable conclusion: based on genetics alone, virtually anyone, whatever their current health, could be flagged as at risk for multiple conditions. Each genome, the team found, contains roughly five million variants, about 10,000 of which alter gene sequences—ranging from traits like lactose intolerance to drug response, though most such changes are biologically neutral. Everyone also carries one to three rare variants previously linked to serious genetic disease, plus around 50 more of uncertain clinical significance.

The team also calculated polygenic risk scores—which combine many genetic factors into an overall disease-risk estimate—across 28 common conditions, including diabetes, cardiovascular disease and schizophrenia, and found most participants fell into the high genetic risk category for about three of them. Since the researchers didn’t assess participants’ actual health status, many of those flagged this way may have no disease at all, underscoring that such results can reflect ordinary genetic variation rather than a looming diagnosis, with other factors playing a major role in whether disease ever develops.

Senior author Professor Caroline Wright said the findings fill a gap in how genomic results get interpreted: “Whole genome sequencing has become such an important tool in diagnosing genetic disease, and we’re increasingly moving toward genetic screening for predicting disease. Yet most people are unaware of just how much genetic variation is present in every genome. Actually, variation is the norm.”

Both biobanks skew toward participants of Western European ancestry, and the researchers note a continued need for more diverse population data. Among participants recruited alongside their parents, the team also found around 63 new, or “de novo,” variants in each genome that weren’t present in either parent, arising mostly from mutations in fathers’ sperm and, to a lesser extent, mothers’ eggs. The number of these new variants rose with paternal age, by about 1.2 additional mutations per year —a finding the researchers say carries implications for reproductive decision-making.

Wright added that context remains essential when acting on genetic test results: “Importantly, we found that everyone carries a small number of genetic variants linked to disease, although many of these will not actually cause disease in that individual. It is therefore crucial to consider context when interpreting findings from genetic testing, including symptoms or family history of disease as well as other clinical and environmental risk factors. Our findings also provide important context for professionals who are interpreting genetic testing results or commissioning genetic screening programs.”
]]> News SEQadmin2 https://www.seqanswers.com/forum/news/327719-exeter-led-study-maps-what-an-average-human-genome-looks-like https://www.seqanswers.com/forum/news/327718-long-read-sequencing-uncovers-cancer-mutations-conventional-testing-missed Thu, 22 Oct 2026 18:48:44 GMT The University of Michigan’s Oncology Sequencing Program, known as MiOncoSeq, analyzes DNA and RNA from patients’ tumors and healthy tissue to find... The University of Michigan’s Oncology Sequencing Program, known as MiOncoSeq, analyzes DNA and RNA from patients’ tumors and healthy tissue to find genetic alterations that can inform treatment. Two new studies from the team, one published in Cancer Discovery and another in the New England Journal of Medicine, show how adding long-read nanopore sequencing to that process can surface genetic changes that conventional sequencing methods overlook entirely.

Long-read sequencing makes it possible to see how complex genetic changes are arranged relative to each other, something conventional methods often can’t resolve. As Arul Chinnaiyan, senior author on both papers, put it: “Having a list of mutations doesn’t always explain a tumor. We need to understand how these mutations are arranged, which conventional sequencing often cannot resolve.” Since most genes exist in two copies, one from each parent, this arrangement matters: nanopore sequencing can reveal whether one or both copies of a cancer-protective gene have been disabled through complex rearrangements or chemical changes, or whether several mutations have stacked up on a single copy of a cancer-promoting gene in ways that boost its activity or fuel drug resistance.

In one part of the Cancer Discovery study, the team screened 768 patients with prostate, breast or ovarian cancer and found 46 tumors showing signs of genomic instability that conventional sequencing couldn’t explain; long-read sequencing resolved 32 of those by uncovering hidden alterations or chemical modifications in protective genes. A broader screen of 4,496 tumor samples from 3,688 MiOncoSeq patients used nanopore sequencing in select cases to map how mutations were arranged in genes including NOTCH1, PDGFRB, KIT and PIK3CA, work the team says can clarify why some patients develop drug resistance and inform treatment decisions. The approach also caught an inherited risk a commercial multigene panel had missed: a woman with a strong family history of breast and ovarian cancer, who had tested negative on that panel, was found through nanopore sequencing of a blood sample to carry a disease-causing insertion in BRCA2, a DNA-repair gene—a finding the researchers hope could help guide genetic counseling for relatives in similar unexplained cases.

The second study traced a rare tumor that appeared beside the spine of a 3-year-old boy 26 months after he received gene therapy for Krabbe disease, an inherited disorder affecting the protective coating of nerve cells. The therapy, delivered after a stem cell transplant, used a modified virus to supply a working copy of the gene missing in Krabbe disease. Nanopore sequencing showed that a fragment of that viral DNA had inserted into the GLI1 gene, carrying genetic switches that drove abnormally high GLI1 activity capable of promoting tumor growth. At the time of the report, the child had no tumor-related symptoms and was being monitored with repeat imaging. “Gene therapy holds great promise, and understanding complications like this can help guide safer design,” Chinnaiyan said. “It is also important to monitor patients over the long term after they receive treatment.”]]> News SEQadmin2 https://www.seqanswers.com/forum/news/327718-long-read-sequencing-uncovers-cancer-mutations-conventional-testing-missed https://www.seqanswers.com/forum/news/327716-mayo-clinic-led-study-detects-dna-mutations-across-noncancerous-tissues Thu, 15 Oct 2026 18:52:55 GMT A Mayo Clinic-led study has shown how to detect a broad range of DNA mutations in noncancerous human tissues and across the genome. The analysis,... A Mayo Clinic-led study has shown how to detect a broad range of DNA mutations in noncancerous human tissues and across the genome. The analysis, drawing on more than 90 trillion DNA letters of sequencing data, could help scientists study when these changes arise, from early development through aging, and how they contribute to cancer and other diseases.

Published in Cell, the study is the flagship paper in a package of roughly a dozen publications from the NIH Common Fund’s Somatic Mosaicism across Human Tissues, or SMaHT, Network. Researchers evaluated approaches for detecting somatic mutations ranging from single-letter DNA changes to large deletions, insertions and rearrangements.

“We often think of the human genome as a single, fixed sequence, but every person is a mosaic of cells that acquire genetic changes over time,” explained Alexej Abyzov, corresponding author of the Cell study. “As we have increasingly recognized in recent years, these mutations are relevant not only to cancer but also to a broad range of age-related diseases.”

Unlike inherited genetic changes, somatic mutations arise after conception and accumulate over a lifetime. As cells divide, they can pass those changes to new cells, creating genetic differences within the same person known as somatic mosaicism. Some somatic mutations can alter how cells behave and contribute to cancer, aging, and neurodevelopmental, cardiovascular and autoimmune diseases.

These mutations can be difficult to detect when they are rare or occur in complex, repetitive regions of the genome, so the SMaHT Network compared short- and long-read whole-genome sequencing, duplex sequencing, single-cell sequencing, and computational approaches. Long-read sequencing produced one of the clearest findings, detecting about twice as many large DNA changes as short-read sequencing and finding insertions that shorter reads often missed. A more complete genome reference also raised precision in one benchmark from 79% to 89%, and single-cell sequencing of 102 lung and colon cells revealed cell-to-cell differences that helped trace their history back to early development.

Dr. Abyzov also co-led a companion SMaHT paper published in The American Journal of Human Genetics, in which deep whole-genome sequencing accurately detected rare, single-letter DNA changes present at levels below 1% in a tissue sample. Analyzing DNA from different organs helped detect mutations that arose early in development and spread to multiple tissues; combining lung and colon data uncovered 13 additional shared mutations, improving detection by 145% for these very rare mutations compared with analyzing either tissue alone.

SMaHT aims to catalog somatic mutations across 10 to 15 tissue types from 150 donors while improving the tools used to detect them. NIH is planning a second stage focused on understanding how these mutations influence biological processes and disease. Dr. Abyzov says the research could eventually help identify people at higher cancer risk and track precancerous changes in tissues before they develop symptoms.]]> News SEQadmin2 https://www.seqanswers.com/forum/news/327716-mayo-clinic-led-study-detects-dna-mutations-across-noncancerous-tissues https://www.seqanswers.com/forum/news/327713-study-finds-chromatin-motion-holds-steady-until-cells-face-stress Wed, 14 Oct 2026 13:39:42 GMT Living human cells appear to hold the local movement of their DNA at a remarkably steady level through most of the cell cycle, only dialing it up... Living human cells appear to hold the local movement of their DNA at a remarkably steady level through most of the cell cycle, only dialing it up when something goes wrong, according to a new study from a team led by Kazuhiro Maeshima at Japan’s National Institute of Genetics.

Genomic DNA is wrapped around core histone proteins to form nucleosomes, the basic units of chromatin, and this dynamic chromatin behavior, tied to chromatin accessibility, plays a critical role in genome functions such as transcription and DNA replication and repair. During interphase, the period between cell divisions, DNA is replicated and the nucleus expands, all while cells continue these essential functions. How DNA’s physical behavior holds up through these large-scale changes had remained unclear. In an earlier study using synchronized human cells, Professor Maeshima’s team found that local chromatin motion stayed nearly constant across the G1, S, and G2 phases. The new study asked whether the same holds true under more natural conditions, in cells growing asynchronously without drug-induced synchronization.

To find out, the researchers combined single-nucleosome imaging with Fucci probes, fluorescent markers that change color as a cell progresses through the cycle, letting them identify each living cell’s cycle stage without chemical synchronization. Using HeLa and HCT116 cells expressing H2B-HaloTag to mark bulk DNA, they tracked individual nucleosomes and matched that movement to each cell’s Fucci signal. Across asynchronously growing cells, average local nucleosome motion remained nearly constant from G1 through S and into G2, even as the genome doubled in content and the nucleus grew substantially in volume.

The team also examined nucleosomes carrying H3.3, a histone variant enriched in active chromatin, or euchromatin. These nucleosomes moved more than bulk H2B-marked nucleosomes overall, but that elevated level of motion likewise stayed constant across interphase, suggesting different chromatin environments each maintain their own characteristic baseline of movement as the cycle progresses.

“Our results show that local DNA motion is maintained at a surprisingly similar level even while DNA is being duplicated and the nucleus is growing,” said Yu Nagata, first author of the study published in Journal of Cell Science. “This near-constant motion may provide similar physical conditions for housekeeping genome functions throughout interphase.”

That stability wasn’t absolute, though. When the researchers inhibited transcription, nucleosome motion increased throughout interphase. Replication stress induced with hydroxyurea and DNA damage induced with cisplatin produced the same effect, each raising average nucleosome motion above its steady baseline.

“Cells seem to maintain local DNA motion near a steady level for routine housekeeping tasks, but they can change this motion when necessary,” Professor Maeshima added. “For example, increased DNA motion after DNA damage may help cells perform ad hoc tasks such as recruiting DNA repair factors.”
]]> News SEQadmin2 https://www.seqanswers.com/forum/news/327713-study-finds-chromatin-motion-holds-steady-until-cells-face-stress https://www.seqanswers.com/forum/news/327712-larger-datasets-reveal-additional-switches-that-control-gene-expression Tue, 13 Oct 2026 17:56:14 GMT Most GWAS loci fall in regions that control gene expression rather than in the genes themselves, and linking those variants to eQTL and sQTL signals... Most GWAS loci fall in regions that control gene expression rather than in the genes themselves, and linking those variants to eQTL and sQTL signals has typically hit a discovery limit after a few thousand samples. A new study published in Science suggests that limit was really a limit of dataset size.

The team analyzed 14,324 RNA sequencing samples, including 6,454 whole blood and 1,291 lung samples, from the NHLBI-sponsored Trans-Omics for Precision Medicine (TOPMed) program. After e/sQTL analysis, they mapped tens of thousands of signals at high resolution. Because TOPMed cohorts are more genetically diverse than most prior studies, roughly one in six signals found in whole blood came from variants that are rare or absent in people of European ancestry, and just 1.3% of those appear in the four large eQTL resources built mostly from European samples.

“The more samples you add, the more e/sQTL signals that you detect,” said co-study leader Steve Parker from the University of Michigan. “I think NHLBI has invested very smartly in TOPMed. Although you saturate discovery of main effects after a few thousand samples… the number of independent e/sQTL signals just keeps on growing and growing, which is really cool to see.”

Fine-mapping GWAS signals from the UK Biobank showed that more eQTL signals also meant more overlap with GWAS findings, and the extra signals weren’t redundant: most genes have several independent regulatory switches, and the second, third, and fourth are harder for smaller studies to detect. Of the 10,611 GWAS signals the team connected to a specific gene, roughly two-thirds involved one of these secondary switches.

“Genetic regulation of the expression levels of one part of a biological unit’s machinery, such as a regulator of a cellular stress response, can affect the expression levels of other parts of the same biological machinery,” explained co-author Laura Scott. Parker added that “genetic evidence of drug targets is a huge predictor of clinical success for therapeutics,” more than doubling the rate of success, making the link between genetic variation and target gene expression especially valuable.

Co-author Francois Aguet noted that “another powerful aspect of larger-scale studies is the ability to identify QTL for rarer variants, which tend to have larger effects. As further such studies are conducted across more tissues and cell types, we will likely find a lot more of these effects.”

The findings also point to the value of expanding beyond whole blood and improving ancestral diversity. “In TOPMed, we still have many more distinct signals to discover at most genes, even in whole blood, which will almost certainly provide still more links between GWAS loci and their likely mechanisms,” noted co-author Laura Raffield. “Also, many non-European ancestry populations are still underrepresented in our current dataset… important ancestry-differentiated signals may be missed, even in blood, and certainly in other tissues. These issues will continue to be addressed in future work from TOPMed.”

“Science moves forward with bigger and better data, always,” Parker said. “It’s the equivalent of getting a fancy new microscope except we’re not seeing things in higher resolution in a microscopy image, we’re seeing things in much higher resolution from a genetic association with gene expression perspective.”
]]> News SEQadmin2 https://www.seqanswers.com/forum/news/327712-larger-datasets-reveal-additional-switches-that-control-gene-expression https://www.seqanswers.com/forum/news/327710-computational-tool-captures-how-chromatin-folds-at-scale Fri, 09 Oct 2026 19:14:25 GMT Studying how chromatin changes requires capturing molecular movements and interactions that are difficult to resolve experimentally. Now, an... Studying how chromatin changes requires capturing molecular movements and interactions that are difficult to resolve experimentally. Now, an international research team led by IRB Barcelona, the University of Cambridge, UT Southwestern Medical Center and the Howard Hughes Medical Institute has developed OpenCGChromatin, a tool that functions as a computational microscope, using simulations to explore how chromatin folds, how its components interact, and what forces hold its structures together.

“The challenge is to connect interactions between individual molecules with the behavior of much larger stretches of chromatin. This tool allows us to study both within the same framework and understand how small molecular changes can alter DNA packaging,” says Modesto Orozco, corresponding author on the study published in Nature Communications.

The tool combines a detailed representation of DNA and proteins with greater computational efficiency, allowing researchers to study chromatin systems more than ten times larger than those accessible to previous models with comparable resolution, including assemblies containing hundreds of nucleosomes. Its simulations reproduce observations from microscopy and biochemical experiments while also revealing movements of flexible histone regions that are difficult to resolve experimentally.

“What Kieran Russell, first author of this study, has achieved is remarkable. He has pushed the state of the art in chromatin modeling, allowing us to simulate systems at a scale and level of molecular detail that were previously out of reach. We can now connect the chemical makeup of chromatin to its organization across scales—from molecular interactions to gene-sized structures and biomolecular condensates—while remaining closely grounded in experiment. I am very excited because OpenCGChromatin opens up a completely new range of questions that we can now address computationally,” says Rosana Collepardo-Guevara e, who also co-led the study.

“The simulations help us understand why changing the spacing between nucleosomes, or adding chemical modifications to histones, can make chromatin behave differently,” adds David Farré-Gil, also an author of the paper.

OpenCGChromatin is available as open-source software, allowing other researchers to use it to investigate the physical principles underlying genome organization.
]]> News SEQadmin2 https://www.seqanswers.com/forum/news/327710-computational-tool-captures-how-chromatin-folds-at-scale https://www.seqanswers.com/forum/news/327703-spatial-transcriptomics-and-metabolite-mapping-combined-on-a-single-tissue-slide Tue, 29 Sep 2026 17:51:30 GMT Spatial transcriptomics (ST) shows which genes are active and where within a tissue, while spatial metabolomics (SM) maps the location of... Spatial transcriptomics (ST) shows which genes are active and where within a tissue, while spatial metabolomics (SM) maps the location of metabolites, the small molecules cells produce and use. A new open, low-cost imaging-based ST platform can now integrate SM on the same slide, addressing two problems that have limited the field: high cost and incompatibility between the two methods.

The platform, called OpenFISH, was described in a study led by Duan Lihui at the Institute of Genetics and Developmental Biology of the Chinese Academy of Sciences, published in Neuron. A biological system can be thought of as a multistory building, with information flowing from genome to transcripts to proteins to metabolites and finally to phenotype, and every layer interacting with the others. Measuring only one layer can miss the full picture and the connections between them. Existing ST technologies can detect molecular features within tissue at single-cell resolution, but they remain expensive and hard for many labs to use, and pairing imaging-based ST with the untargeted SM method MALDI-MSI on the same tissue section adds a further challenge.

To bring costs down, the researchers used a modular probe design along with a simple gene-coding system that removes the need for a microfluidic system, and they streamlined the experimental procedure so wet-lab time runs no more than 13 hours. A standard 20x widefield fluorescence microscope is enough to capture clear signals in situ. Together, these changes cut OpenFISH's total cost by about 95 percent compared with leading commercial platforms.

The team tested OpenFISH in two neuroscience applications: tracking cell-type-associated transposable element (TE) elevation during inflammation, and examining neuronal cell lamination distortion after knocking out the Reln gene. Reproducible TE upregulation pointed to TEs as active drivers or modulators of neuroinflammatory pathways, and beyond the known anatomical effects of Reln knockout, the researchers also found a decrease in D1-type inhibitory striatal neurons.

Because ST and SM are usually run on separate, adjacent tissue sections, differences between those sections can complicate interpretation. To combine both methods on one section, the researchers modified conductive glass slides for MALDI-MSI, using polyacrylamide gel embedding, protein digestion, and lipid removal so that OpenFISH signals remained detectable even after the harsh laser processing MALDI-MSI requires. Ion feature signals and transcript detection were barely affected by this integration, and the combined pipeline revealed cell-type-associated metabolites in mouse brain cells, with the merged modalities improving anatomical depiction.

Applied to 5xFAD mice, a model for Alzheimer's disease, the pipeline showed that microglia had the strongest changes, with multiple cell-type-associated metabolites elevated compared with healthy controls. The researchers describe the work as introducing a cost-effective ST tool that pairs with SM platforms to help untangle complex molecular interactions in biological systems.
]]> News SEQadmin2 https://www.seqanswers.com/forum/news/327703-spatial-transcriptomics-and-metabolite-mapping-combined-on-a-single-tissue-slide https://www.seqanswers.com/forum/news/327691-bat1k-consortium-combines-genomes-and-fossils-to-trace-bat-origins Fri, 25 Sep 2026 17:06:42 GMT An international consortium has sequenced and compared 103 bat genomes spanning all 21 recognized bat families, then combined that genomic dataset... An international consortium has sequenced and compared 103 bat genomes spanning all 21 recognized bat families, then combined that genomic dataset with information from 44 bat fossils to reconstruct how bats evolved their extraordinary biology. The study, led by researchers at the University of St Andrews as part of the Bat1K consortium, was published in Nature.

Bats make up roughly one in five mammal species and are the only mammals capable of powered flight, but their evolutionary history has been difficult to pin down using fossils or genetics alone. By sequencing genomes from across the full breadth of living bat diversity and integrating that data with the fossil record, the consortium built a more complete picture of bat evolution than either approach could produce on its own.

The genomic sequencing effort allowed the team to computationally reconstruct the ancestral bat genome, tracing the genetic changes that gave rise to traits such as echolocation and flight across the bat family tree. Comparing genomes across all 21 families also let researchers identify the genes and genetic changes associated with these specialized adaptations, linking specific sequence differences to the biological features that distinguish bat lineages from one another.

Combining this genomic resource with the fossil dataset gave the researchers a new way to date bat origins. According to Prof. Liliana M Dávalos, “The approach we used to model the evolution of fossil and living species together can do what other methods cannot: identify the oldest group of fossil bats while taking the genomic data into account, and uncover when and where bats originated.”

The scale of the genomic resource itself reflects years of coordinated sequencing work across the consortium. Prof. Sonja Vernes, who leads the Bat1K initiative, said, “Bats constantly surprise us. They are one of evolution’s greatest experiments. This extraordinary genomic resource, the culmination of years of international cooperation of Bat1K, is finally allowing us to understand how their remarkable biology evolved.”

By pairing whole-genome sequencing across the entire bat order with fossil-informed modeling, the study offers a genomic framework other researchers can use to investigate the molecular basis of bat-specific traits, and demonstrates how integrating large-scale comparative genomics with paleontological data can resolve evolutionary questions that neither dataset could answer alone.
]]> News SEQadmin2 https://www.seqanswers.com/forum/news/327691-bat1k-consortium-combines-genomes-and-fossils-to-trace-bat-origins