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Lars Bullinger, Jinghui Zhang, Jeffery Klco, James Downing and colleagues report a detailed genomic analysis of pediatric and adult core-binding factor acute myeloid leukemias (CBF-AMLs). They identify recurrent mutations in CCND2, MGA, DHX15 and ZBTB7A and highlight dramatic differences in the landscape of cooperating mutations between different CBF-AML subtypes.

A large-scale genomics study shows that the cell of origin and founding mutations determine disease subtype and lead to the expression of multiple haematopoietic lineage-defining antigens in mixed phenotype acute leukaemia.

Proteins involved in epigenetic regulation are frequently mutated in several paediatric cancers. Here, Huether et al.characterize the somatic mutation frequency across 21 paediatric cancer subtypes by sequencing 633 epigenetic genes in over 1,000 tumours; generating a rich data set for investigating epigenetic dysregulation.

Vaccination is effective in protecting from COVID-19. Here the authors report immune responses and breakthrough infections in twice-vaccinated patients receiving anti-TNF treatments for inflammatory bowel disease, and find dampened vaccine responses that implicate the need of adapted vaccination schedules for these patients.

The retinoblastoma genome is shown to be stable, but multiple cancer pathways are identified that are epigenetically deregulated, providing potential new therapeutic targets.

A study of the evolution of the SARS-CoV-2 virus in England between September 2020 and June 2021 finds that interventions capable of containing previous variants were insufficient to stop the more transmissible Alpha and Delta variants.

Analysing human B-cell acute lymphoblastic leukaemias, this study maps the genetic heterogeneity of cells within a given tumour sample and the evolutionary path by which different subclones have emerged. Leukaemia-initiating cells that transplant the disease mirror the genetic variegation of the bulk tumours, providing insights into the heterogeneity of these functional subpopulations at the genetic level. This has implications for therapeutic approaches targeting the tumours and specifically leukaemia-initiating cells.

Clinical oncology is rapidly adopting next-generation sequencing technology for nucleotide variant and indel detection. Here the authors present a three-platform approach (whole-genome, whole-exome, and whole-transcriptome) in pediatric patients for the detection of diverse types of germline and somatic variants.

Typhoid fever is caused by the bacterium Salmonella Typhi. Here, Park et al. analyse the genomes of 249 S. Typhi isolates from 11 sub-Saharan African countries, identifying genes and plasmids associated with antibiotic resistance and showing that multi-drug resistance is highly pervasive in sub-Saharan Africa.

The genes underlying stripe rust host specificity between wheat and barley remain unknown. Here, the authors report that Rps6, Rps7 and Rps8 determine host species specificity in barley at different stages of the pathogen lifecycle and the barley powdery mildew immune receptor Mla8 and Rps7 are the same gene.

Genomic analysis of neuroblastoma has revealed important disease etiology. In this study, the authors assembled whole genome, exome and transcriptome data from over 700 neuroblastomas and identified molecular signatures correlated with age, and rare, potentially targetable variants overlooked in smaller cohorts.

This algorithm uses the soft-clipped, unaligned parts of a sequence read to map structural variation in cancer genomes with high predictive accuracy.

Two doses of the coronavirus disease 2019 vaccine ChAdOx1 nCoV-19 boost antibody responses and functions in phase 1/2 trial participants.

Genetic heterogeneity and clonal evolution contribute to cancer progression. Here Ma et al.use deep whole-exome sequencing to identify recurrently mutated pathways and clonal architecture in pediatric acute lymphoblastic leukaemia, shedding light on the evolutionary trajectory from diagnosis to relapse

The second plague pandemic, caused by Yersinia pestis, started in the 14th century and recurred in Europe until the 18th century. Here, the authors reconstruct ancient Y. pestis genomes from human remains spanning this period, shedding light into the phylogeography and population structure of the European strains.

At least two-thirds of supratentorial ependymomas contain oncogenic fusions between RELA, the principal effector of nuclear factor-κB (NF-κB) signalling, and uncharacterized gene C11orf95; C11orf95–RELA fusion proteins translocate spontaneously to the nucleus to activate NF-κB target genes, and rapidly transform neural stem cells to form tumours in mice

Randomised controlled experiments are the gold standard for scientific inference, but environmental and social scientists often rely on different study designs. Here the authors analyse the use of six common study designs in the fields of biodiversity conservation and social intervention, and quantify the biases in their estimates.

Sequencing of the genome of the butterfly Heliconius melpomene shows that closely related Heliconius species exchange protective colour-pattern genes promiscuously.

Using high-coverage targeted next-generation sequencing, this report provides a catalog of genetic alterations in colorectal and lung cancers, identifying previously unknown alterations, such as JAK2 mutations and KIF5B-RET fusions, that may represent druggable targets.

Whole-genome sequencing of medulloblastoma samples reveals several recurrent mutations in genes not previously implicated in the disease, many of which affect components of the epigenetic machinery in different disease subgroups.

Reducing agricultural emissions during times of increasing food demand is a challenge. Research, using the UK as an example, now shows the technical mitigation potential of increasing agricultural yields, reducing farmed area and restoring habitats.

Current approaches for volumetric super-resolution microscopy can yield large and complex PSF spatial footprints. Here, the authors show a super-resolution microscopy approach using a hexagonal microlens array, which offers speed improvements in volumetric imaging compared to other single-molecule methods.

In most cancers, mutations that lead to oncogene activation and tumor suppressor inactivation synergize to promote tumorigenesis. However, in neuroblastomas, MYCN amplification and ATRX mutations are mutually exclusive and incompatible.

In this study, the authors show that topoisomerase-1–DNA cleavage complex (Top1cc) accumulation may be involved in the onset of ataxia telangiectasia and spinocerebellar ataxia with axonal neuropathy 1. In addition, they find that ATM regulates Top1cc levels in a kinase activity– and double-stranded break repair–independent manner.

Charles Mullighan, Jinghui Zhang and colleagues characterize a subtype of B-progenitor acute lymphoblastic leukemia with deregulated DUX4 and ERG. They find that aberrant DUX4 activation results in loss of ERG function, either through deletion or by the induction a novel transforming ERG isoform, ERGalt, that inhibits wild-type ERG activity.

Chromothripsis and chromoanasynthesis lead to locally clustered rearrangements affecting one or a few chromosomes, but their impact on cancer development and progression is unclear. Here the authors analyse the role of DNA repair factors in brain tumors by whole-genome sequencing of tumors from mouse models of medulloblastoma or high grade gliomas.

Pediatric adrenocortical carcinoma is a rare malignancy with poor prognosis. Here the authors analyse the genomes, exomes and transcriptomes of 37 such tumours and identify genetic alterations whose nature, timing and potential interactions are key events with prognostic significance in pediatric adrenocortical tumorigenesis.

Olivine crystals with prominent intracrystalline distortions have previously been used to quantify deformational processes within the mantle. Here, the authors show that similar techniques can be applied to deformed volcanic olivine crystals, providing quantitative constraints on the geometry of melt-rich mush piles within magmatic plumbing systems.

ABCC4 is a chemotherapeutic drug exporter highly expressed in acute myeloid leukemia. Here, the authors demonstrate that MPP1 anchors ABCC4 to the outer cell membrane mediating drug resistance in leukemic cells and identify antimycin A as a chemical probe that disrupts such interaction and restores sensitivity.

Romer’s Gap describes the period with few known fossils when early tetrapods were becoming increasingly terrestrial. Here, five new species, three stem tetrapods and two stem amphibians, are described from a location in Scotland shedding light on the phylogeny and environment of this period.

The C. elegans PIWI protein PRG-1 resides in the membraneless organelle P granule. Here, the authors identify the constitutive P granule protein DEPS-1 as an interactor of PRG-1 and show its function in piRNA-dependent silencing. DEPS-1 and PRG-1 form elongated condensates in vivo.

The MiDAC complex recruits class I histone deacetylases to chromatin but little is known about its precise structure and function. Here, the authors explore the role of MiDAC in the cell cycle and during mouse embryogenesis, and present cryoEM structures that provide insight into MiDAC’s mode of assembly.

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.

Variably methylated intracisternal A particle (VM-IAP) retrotransposons are stable across the murine lifespan. VM-IAP retrotransposons are unaffected by maternal exposure to the endocrine disruptor bisphenol A, an obesogenic diet or methyl donor supplementation.