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Artifact mutations from FFPE are a major barrier blocking WGS adoption in clinical oncology. FFPErase, a machine learning framework, eliminates these with high accuracy in multiinstitutional datasets, delivering clinical-grade variant reports.

Defective DNA interstrand crosslink repair in Fanconi anaemia drives extensive genomic rearrangements, thereby substantially increasing the risk of cancer development.

Whole-genome sequencing data from more than 2,500 cancers of 38 tumour types reveal 16 signatures that can be used to classify somatic structural variants, highlighting the diversity of genomic rearrangements in cancer.

A pan-cancer genomic analysis reports the effects of structural variations on chromatin domains (TADs). Most TAD disruptions do not result in appreciable changes in expression of nearby genes.

Ionizing radiation may induce irreparable DNA damage leading to cancer. Here, the authors identify a specific signature of mutations arising in patients exposed to ionizing radiation and suggest that radiation-induced tumorigenesis is associated with higher rates of genome-wide deletions and balanced inversions.

This study characterizes the three-dimensional (3D) genome architecture of 15 primary human cancer types from The Cancer Genome Atlas. The analyses identify different archetypes of enhancer usage and enhancer rewiring events due to different classes of mutations and structural variants.

Defects in homologous recombination (HR) are found in some triple negative breast cancers, suggesting they may be sensitive to PARP inhibitors. In this phase II clinical trial of the PARP inhibitor rucaparib, changes in Ki67 levels did not correlate with markers of HR deficiency but HR deficiency was detected in 69% of tumours, indicating that PARP inhibitors may be a useful treatment.

The efficacy of immune checkpoint inhibitors (ICI) in osteosarcoma has been limited. Here, the authors investigate the immunogenomic landscape of osteosarcoma, and integrated analyses highlight features related to a suppressed immune microenvironment.

Using SCN2A haploinsufficiency as a proof-of-concept, upregulation of the existing functional gene copy through CRISPR activation was able to rescue neurological-associated phenotypes in Scn2a haploinsufficient mice and human neurons.

The anisotropy of acoustic velocity changes is investigated and modelled during damage and recovery sequences in sandstone. The results highlight the role of sliding and aging of oblique grain-to-grain contacts in temporal changes of elastic properties, a phenomenon known as slow dynamics.

Whole-genome sequencing of tumours from 560 breast cancer cases provides a comprehensive genome-wide view of recurrent somatic mutations and mutation frequencies across both protein coding and non-coding regions; several mutational signatures in these cancer genomes are associated with BRCA1 or BRCA2 function and defective homologous-recombination-based DNA repair.

Chordoma is a rare often incurable malignant bone tumour. Here, the authors investigate driver mutations of sporadic chordoma in 104 cases, revealing duplications in notochordal transcription factor brachyury (T), PI3K signalling mutations, and mutations in LYST, a potential novel cancer gene in chordoma.

Genomic and transcriptomic analysis of 470 mostly high-risk neuroblastomas collected from 283 patients delineates subtype-specific evolutionary patterns and progression-related convergent evolution and describes the clonal dynamics of metastases.

Efficient, large-scale genomic analysis is facilitated on the cloud by a computational tool with error-diagnosing and self-healing capabilities.

Colin Cooper and colleagues report genome-wide sequences of multiple samples of multifocal cancer and morphologically normal tissue from the prostates of three men. They found high levels of mutations in morphologically normal tissue distant from the cancer, consistent with field effects.

Previous work has shown the detection of quantum turbulence with mechanical resonators but with limited spatial and temporal resolution. Here, the authors demonstrate real-time detection of single quantum vortices in superfluid ⁴He with millisecond and micron resolution at temperatures of 10 millikelvin.

Brain morphology is complex, heterogenous and miniaturized—and notoriously difficult to visualize. Dembitskaya et al. show how fluorescence ‘shadow imaging’ gives detailed and comprehensive access to the cellular architecture of the mouse brain in vivo.

Joint analysis of new and previously published sequencing data for primary and metastatic prostate cancers identifies new candidate driver mutations and provides insights into disease progression and potential drug targets.

Mutations in human pluripotent stem cells (PSC) and whether any form during culture prior to use in a human clinical context are a concern. Here, the authors use hPSCs derived to cGMP standards and show they have low mutation rates after culture, noting this decreases on culturing in low (5%) oxygen conditions.

Andrew Futreal and colleagues identify the major cartilage collagen gene COL2A1 as a frequent target of somatic mutation in chondrosarcoma. The mutation patterns are consistent with selection for variants likely to impair normal collagen biosynthesis.

Scars are a significant problem caused by excess collagen in the skin. Here the authors develop a topical drug that reduces collagen stability and leads to improved scar appearance and stiffness in preclinical models.

Circadian clocks are critical timing regulators of physiology and behaviour that are ubiquitous in eukaryotes. Most mechanistic models of the this clock are based on transcription cycles, but some evidence for post-translational regulation has recently surfaced in plants and cyanobacteria. This is one of two groups demonstrating a role for the oxidation of peroxiredoxin proteins in maintaining an entrainable oscillation in human red blood cells and a unicellular alga. These data indicate a role for non-transcriptional mechanisms in clock models and open the door to future work exploring the connections between the transcriptional and non transcriptional circadian machinery.

Nik-Zainal and colleagues leverage CRISPR–Cas9 and whole-genome sequencing to examine mutational patterns following knockout of 42 human DNA repair genes. They further develop and validate a clinically relevant tool to detect mismatch repair-deficient tumors.

An on-chip nano-bolometer integrated with a Josephson junction quantitatively measures the Josephson radiation up to about 100 GHz frequency. This wide-band, thermal detection scheme of microwave photons provides a sensitive detector of Josephson dynamics beyond the standard conductance measurements.

Stimuli-responsive elastic metamaterials enable a high degree of tunability of resonance-based features. Here, a magnetically programmable metamaterial based on magnetorheological elastomers is designed and fabricated, demonstrating robust local resonance bandgap control.

Determining the nanostructure within complex composites may lead to greater understanding of their properties. Here, the authors demonstrate the application of X-ray atomic pair distribution function computed tomography to resolve the physicochemical properties of palladium nanoparticles on an alumina catalyst.

The FANCM helicase functions in limiting crossovers (COs) by unwinding inter-homolog repair intermediates. Here, the authors generate null mutants of fancm in tetraploid and hexaploid wheat and show that FANCM promotes class I interfering COs and suppresses class II noninterfering COs in wheat meiosis.

Unlocking the ultimate potential of superconducting nanowire single photon detectors requires engineering their thermal properties. Here, the authors improve our understanding of heat flow in these devices and suggest routes to improved performance.

Toxin B (TcdB) is a major exotoxin responsible for diseases associated with C. difficile infection. Here, Tian et al. show that several TcdB subtypes do not recognize the established FZD receptors, and identify a different host protein (TFPI) as a receptor for subtypes TcdB4 and TcdB10.

Whole-genome sequencing of normal bronchial epithelium from 16 individuals shows that tobacco smoking increases genomic heterogeneity, mutational burden and driver mutations, whereas stopping smoking promotes replenishment of the epithelium with near-normal cells.

Somatic mutations obtained from laser microdissected biopsies of human tissues are used to reconstruct the developmental phylogenies of these tissues back to the zygote.

The chemotherapeutic agent CX-5461 is shown to be a potent mutagen in hTERT-RPE1, HAP1 and human induced pluripotent stem cells. The compound generates distinct mutational patterns of single- and double-base substitutions, as well as of small insertions and deletions, that were detectable following a single exposure.

Osteosarcoma is a primary malignancy of bone that affects children and adults. Here, the authors sequence childhood and adult osteosarcomas, identifying mutations in insulin-like growth factor signalling genes and distinct genomic rearrangement profiles characterized by chromothripsis-amplification.

Determining active species in non-precious metal catalysts for the oxygen reduction reaction remains a challenge due to catalyst heterogeneity. Here the authors perform gas-phase treatments on an iron-based catalyst to allow the identification of carbon-encapsulated iron nanoparticles as the active species.

A study describes a wood-based, three-tailed, biodegradable seed carrier that self-drills into the ground in response to moisture fluctuations with a success rate higher than that of natural self-drilling seeds.

When strain is applied to strontium ruthenate, superconductivity emerges at a different temperature to the breaking of time-reversal symmetry. This indicates that the superconductivity could have a chiral d-wave order parameter.

Healthy tissues from individuals with germline mutations in POLE or POLD1 show increased mutational burden, suggesting that normal cells are capable of tolerating high mutation rates.

Here, Hiatt et al. report the knock-out of over 400 genes in primary CD4+ T cells to assess their functional role in HIV replication, finding 86 initial candidates of which 47 are validated as HIV host factors, including 23 with restrictive activity.

A high-bandwidth neuromotor interface offers performant out-of-the-box generalization across people.

Adrienne Flanagan and colleagues identify distinct driver mutations in H3F3A and H3F3B in chondroblastoma and giant cell tumor of bone. The mutations occur in over 90% of tumors and exhibit a high degree of tumor type specificity.