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DNA probes used in next generation sequencing (NGS) have variable hybridisation kinetics, resulting in non-uniform coverage. Here, the authors develop a deep learning model to predict NGS depth using DNA probe sequences and apply to human and non-human sequencing panels.

This study analysed genetic data of soil-transmitted helminths from 27 countries, revealing diversity impacting molecular test accuracy and highlighting the need to adapt diagnostics for effective STH surveillance.

Mitochondria are essential cellular components that are found in animals, plants, fungi, and protists. This study reports what is believed to be the first example of complete mitochondrial loss in a free-living organism, providing insights into the evolutionary plasticity of eukaryotic cells.

The first genome sequence of an ancient human is reported. It comes from an approximately 4,000-year-old permafrost-preserved hair from a male from the first known culture to settle in Greenland. Functional single-nucleotide polymorphism (SNP) assessment is used to assign possible phenotypic characteristics and high-confidence SNPs are compared to those of contemporary populations to find those most closely related to the individual.

nELISA miniaturizes the sandwich immunoassay and transforms it into a massively scalable platform for quantitative proteomics.

Together with a companion paper, molecular details of immune responses in a pig-to-human xenotransplantation are identified through dense longitudinal multi-omics profiling of the xenograft and the host recipient, across the 61-day procedure.

Ganguli et al. show that CDKN2A loss in Barrett’s esophagus prevents esophageal adenocarcinoma initiation by counterselecting subsequent TP53 loss and report context-dependent effects of 9p21 gene co-deletions on disease progression.

Single-cell Proliferation Rate Inference in Non-homogeneous Tumors through Evolutionary Routes (SPRINTER) allows users to infer proliferation rates of individual clones within a tumor from single-cell DNA sequencing data. Applying SPRINTER to human tumor datasets highlighted a link between proliferation and metastatic potential.

Wastewater treatment plants are important reservoirs of antibiotic resistance genes (ARGs). Here, the authors analyze ARGs in a global collection of samples from wastewater treatment plants across six continents, providing insights into biotic and abiotic mechanisms that appear to control ARG diversity and distribution.

Primary prostate tumours are known to be genetically heterogeneous and clonal selection has the potential to drive metastasis. Here Hong et al. show that the acquisition of TP53 mutations is linked to clonal expansion and metastatic progression to lethality.

Spatial orientation of cells in an interconnected network is lost in high-throughput single-cell epigenomic assays. Here the authors present sciMAP-ATAC to produce spatially resolved single-cell ATAC-seq data.

This Article details the methods used for rigorous assessment of disease interventions in a multicenter preclinical trial. Using stroke models as proof of concept, it offers adaptable protocols for any field requiring robust preclinical validation.

Long-term imaging in the spinal cord is achieved by placing a fluoropolymer membrane on the spinal cord, which reduces fibrosis. This approach, combined with deep-learning-based motion correction, enables months-long imaging of the same neurons.

Mixed responses to targeted therapy within a patient are a clinical challenge. Here the authors show that TP53 loss-of-function cooperates with whole genome doubling which increases chromosomal instability. This leads to greater cellular diversity and multiple routes of resistance, which in turn promotes mixed responses to treatment.

Multielectron quantum dots offer a promising platform for high-performance spin qubits; however, previous demonstrations have been limited to single-qubit operation. Here, the authors report a universal gate set and two-qubit Bell state tomography in a high-occupancy double quantum dot in silicon.

The downscaling process of conventional static random-access memory (SRAM) cells has recently slowed down, posing challenges for future electronic devices. Here, the authors demonstrate ~40% reduction in cell area and improved interconnect length for 2-tier 3D-integrated SRAM cells based on 2D MoS₂ transistors.

Gut bacteria digest dietary fiber and release molecules as energy for the host. Here, Yu et al. find that the ability of certain gut bacteria to digest different fibers influences host consumption of food containing these fibers.

Symbiont-housing structures are well-studied in multicellular eukaryotes but rarely in unicellular protists. This study shows that low-oxygen-adapted Anaeramoebae have symbiosomes positioning sulfate-reducing bacteria near hydrogenosomes, with genomic analyses suggesting likely metabolic interactions.

A floating-gate memristive device fabricated in a commercial 180 nm CMOS process can be integrated into a selector-free memristive array and used to demonstrate basic neuromorphic applications.

Whole-genome sequencing data for 2,778 cancer samples from 2,658 unique donors across 38 cancer types is used to reconstruct the evolutionary history of cancer, revealing that driver mutations can precede diagnosis by several years to decades.

In single-cell RNA-seq analyses, it would be critical to measure the relationships between genes. Here, the authors develop a framework for single-cell dimensionality reduction that incorporates gene-specific relationships - GeneVector -, and use it for tasks such as annotating cell types and analysing pathway variation after treatment.

Fault tolerance is essential for reliable AI acceleration using novel memristive hardware. Yousuf et al. developed a training-free fault tolerance scheme and demonstrated on a 20,000-memristor prototyping platform that it outperforms other solutions.

Here, Siranosian et al. provide evidence for rare transmission of commensal and pathogenic bacteria between the microbiomes of hospitalized adults, with important factors being roommate overlap and exposure to broad-spectrum antibiotics.

In this work, Wilson et al., examined sharing of Salmonella between humans, animals and the environment using household samples from Malawi. They revealed an interconnected web of Salmonella circulation, underscoring the importance of the One Health concept.

One-dimensional molecular arrays on graphene field-effect transistors can be reversibly switched between different periodic charge states by tuning the graphene Fermi level via a back-gate electrode and by manipulating individual molecules, allowing them to function as a nanoscale shift register.

Gain-of-function mutations altering the PWWP domain of DNMT3A are identified as a new cause of microcephalic dwarfism. These mutations abrogate DNMT3A binding to H3K36me2 and H3K36me3 and lead to aberrant DNA methylation of Polycomb-marked regions.

The Somatic Mosaicism across Human Tissues Network aims to create a reference catalogue of somatic mosaicism across different tissues and cells within individuals.

The combination of computational design, laboratory-based screening and biophysical validation enables the de novo generation of variable heavy-chain antibody fragments and antibodies that precisely target chosen disease-related molecules.

Effects of reproductive systems on crop genomic variation and breeding remain unclear. Here, the authors report that reproductive types impact genomic landscapes and grapevine breeding based on comparative genomic and population genetic analyses of wild grapevine and a complex pedigree of Pinot Noir.

Human primary monocytes reversibly phase separate into regular, multicellular, multilayered domains on soft matrices with physiological stiffness due to local activation and global inhibition processes that occur during random cell migration.

Genomic and phenomic screens of 827 wheat landraces from the A. E. Watkins collection provide insight into the wheat population genetic background, unlocking many agronomic traits and revealing haplotypes that could potentially be used to improve modern wheat cultivars.

Around 1 in 136 pregnancies is lost due to a pathogenic small sequence variant genotype in the fetus.

We demonstrate an avalanche photodiode design using photon-trapping structures to enhance the quantum efficiency and minimizing the absorber thickness, yielding high quantum efficiency, suppressed dark current density and bandwidth of ~7 GHz.

Constructing genome graphs directly from genome assemblies overcomes single-reference bias.

In a mouse model of the rare disease citrin deficiency, the authors discovered that the accumulation of glycerol-3-phosphate leads to ChREBP activation and FGF21 induction. The study identifies glycerol-3-phosphate as a ChREBP-activating ligand, which could resolve paradoxes of FGF21 expression and clarify the logic of lipogenic transcription.

The GREGoR consortium provides foundational resources and substrates for the future of rare disease genomics.

A new approach for whole-genome sequencing of plasma circulating tumor DNA allows for dynamic monitoring of disease burden and ultra-sensitive detection of minimal residual disease.

Transcriptomic profiling of human skin serially sampled from wound margin during long surgeries reveals tissue damage and inflammation-related gene signatures relevant to human post-operative wound recovery and postoperative pain.

How transposable elements (TE) contribute to cell fate changes is unclear. Here, the authors generate a pipeline to quantify TE expression from single cell data. They show the dynamic expression of TEs from gastrulation to somatic cell reprogramming and human disease

Unconventional unidirectional magnetoresistance observed in the heterostructures of a topological semimetal (WTe₂) and a magnetic insulator (Cr₂Ge₂Te₆) enables the electrical read-out of the magnetic states of a perpendicularly polarized magnet through longitudinal resistance measurements.

Results of an early-phase breast cancer prevention trial demonstrate the potential for breast cancer prevention in premenopausal women with anti-progestin therapy by inducing epithelial–stromal remodelling and suppression of luminal progenitors.

Studies have shown that placental aneuploidy is correlated with adverse pregnancy outcomes, though few causative data are available. Here they show that chromosomal instability is an inherent feature of trophoblasts and normal human placentas, without functional compromise, and provide mechanisms for how this damage is tolerated.

Myeloid-specific mechanotransduction ablation downregulates pro-fibrotic fibroblast transcriptional profiles to reduce scar formation in human cells

The number of usable reads in single-cell DNA and chromatin assays is increased by adapter switching.

This study describes the integrative analysis of 111 reference human epigenomes, profiled for histone modification patterns, DNA accessibility, DNA methylation and RNA expression; the results annotate candidate regulatory elements in diverse tissues and cell types, their candidate regulators, and the set of human traits for which they show genetic variant enrichment, providing a resource for interpreting the molecular basis of human disease.

Neural mechanisms underlying flexible learning and decision-making are not fully understood. Using single-cell calcium imaging, authors here found that neurons in orbitofrontal and secondary motor cortex exhibit complementary roles in reward learning, with neurons in the former exerting a sustained role in conditions of uncertainty.

The epigenetic changes underlying the heterogeneity of RA disease presentation have been the subject of intense scrutiny. In this study, the authors use multiple single-cell sequencing datasets to define ‘chromatin superstates’ in patients with RA, which associate with distinct transcription factors and disease phenotypes.