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A single-cell multiomic immune cell atlas from 235 Japanese, including patients with COVID-19 and healthy individuals, linked with host genetics including germline and somatic mutation, plasma proteomics and metagenomics data reveals that immune cells are dynamically regulated in a cell state-dependent manner.

Natural scenes sparsely activate V1 neurons. Here, the authors show that a small number of active cells reliably represent visual contents of a natural image across trials regardless of response variability, due to the diverse and partially overlapping representations of individual cells.

Genetic mechanisms influencing COVID-19 susceptibility are not well understood. Here, the authors analyzed whole blood RNA-seq data of 465 Japanese individuals with COVID-19, highlighting thousands of fine-mapped variants affecting expression and splicing of genes, as well as the presence of COVID-19 severity-interaction eQTLs.

A genome-wide association study highlights a variant in DOCK2, which is common in East Asian populations but rare in Europeans, as a host genetic risk factor for severe COVID-19.

Analysis of the blood DNA virome in patients with COVID-19 and autoimmune disease associates endogenous HHV-6 (eHHV-6) and high anellovirus load with increased disease risk, most notably for systemic lupus erythematosus. eHHV-6 carriers show a distinct immune response.

Myelodysplastic syndromes are a broad group of haematopoietic malignancies that often progress to acute myeloid leukaemia. Here, the authors show that linear and branched evolution occurs within myelodysplastic syndrome and these patterns can be impacted by treatment.

High-efficiency fluorescent organic light-emitting diodes have been realized by employing custom-designed molecules that make it possible to convert non-radiative triplet states into radiative singlet states.

Genes in the rodent brain are knocked down by DNA/RNA heteroduplexes injected intravenously.

Seishi Ogawa and colleagues report the landscape of somatic mutations in Down syndrome–related myeloid disorders. They identify recurrent mutations in multiple cohesin components, CTCF and epigenetic regulators in Down syndrome–related acute megakaryoblastic leukemia.

Peripheral blood mononuclear cells from 73 Japanese patients with coronavirus disease 2019 (COVID-19) and 75 healthy controls were analyzed using single-cell transcriptomics. Combining these data with genotyping data highlights the interplay between host genetics and the immune response in modulating disease severity.

Persistent DNA lesions can occur throughout the human lifespan and can remain in the genome of affected cells for several years and generate a substantial proportion of the mutational burden.

Jaroslaw Maciejewski, Seishi Ogawa and colleagues examine the clonal dynamics of myelodysplastic syndromes (MDS) by analyzing whole-exome and targeted sequencing data from a large patient collection. They find that progression steps previously defined by pathologic criteria are accompanied by distinct molecular changes, and they show that driver genes can be classified into molecular subtypes differentially associated with low-risk MDS, high-risk MDS or secondary acute myeloid leukemia.

Seiji Kojima and colleagues report whole-exome sequencing of 13 juvenile myelomonocytic leukemias. They identify RAS pathway mutations in 82 of the 92 total cases analyzed and mutations in SETBP1 or JAK3 in 16 cases.

The molecular heterogeneity of KMT2A-rearranged infant acute lymphoblastic leukemia (ALL) remains poorly characterised. Here, the authors perform multi-omics analysis for 84 ALL patients and suggest 5 distinct subgroups for risk stratification and personalised treatment.’

In chronic myeloid leukaemia (CML), the drivers of blast crisis and resistance to tyrosine kinase inhibitors are not fully characterised. Here, the authors analyse a cohort of CML samples with genomic technologies and find that at least one driver alteration is associated with progression and worse prognosis.

By using phylogenetic analyses of multiple microdissected samples from both cancer and non-cancer lesions, unique evolutionary histories of breast cancers harbouring a common driver alteration are shown, providing new insight into how breast cancer evolves.

Genome sequencing of fractionated T-, B- and natural killer cells from patients with chronic active Epstein–Barr virus (EBV) infection sheds light on the nature of the EBV-infected progenitor and suggests a link between intragenic EBV deletions and EBV-associated neoplastic proliferations.

In patients with ulcerative colitis, chronic inflammation can lead to remodelling of the colorectal epithelium through positive selection of clones with mutations in genes related to IL-17 signalling, which, however, might be negatively selected during colitis-associated carcinogenesis.

Stepwise acquisition of mutations gives rise to myelodysplastic syndrome (MDS) in older adults. Here, the authors infer the clonal hierarchy of 1809 MDS patients, revealing insights into the evolution of dominant/secondary mutations and how these impact clinical phenotypes like leukemic progression and therapy response.

Authors develop and present RIBEA (Rapid and Integrated Bacterial Evolution Analysis), an approach that combines lab-based evolution experiments, genome sequencing and in vivo testing, to monitor long-term evolution or bacterial pathogenicity and antimicrobial resistance, in the context of Klebsiella pneumoniae.

Rhabdomyosarcoma is a common childhood soft-tissue cancer. Here Seki and Nishimura analyse the exome, transcriptome, copy number and DNA methylome of 60 sarcomas and identify distinct methylation subgroups associated with genetic and clinical features.

Myelofibrosis is a myeloproliferative neoplasm. Here, the authors show the clonal evolution of myelofibrosis during JAK inhibitor therapy, revealing how the treatment results in an increase in clonal complexity and a gain of RAS pathway mutations.

In physiologically normal epithelia, age-related expansion of clones that carry mutations in NOTCH1 and other driver genes is accelerated by risk factors for developing oesophageal squamous cell carcinoma, such as alcohol consumption or smoking.

Seishi Ogawa and colleagues report the results of a large-scale sequencing study of adult T cell leukemia/lymphoma. They find recurrent alterations enriched for T cell receptor/NF-κB signaling, T cell trafficking and other T cell pathways and highlight targets for the development of new therapeutics for this intractable cancer.

Kim and colleagues perform a phase 2 clinical trial (ELM-2) of odronextamab monotherapy in patients with relapsed/refractory diffuse large B cell lymphoma and report on the primary analyses of the efficacy and safety profile.

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.

Mutations to the splicing machinery may have an important role in myelodysplasia. Here, the authors describe splicing factor gene mutations in myelodysplasia and report tumor suppressor, epigenetic, iron metabolism and heme biosynthesis genes as their targets.

Seishi Ogawa, Atsushi Natsume and colleagues report analyses of large sets of sequence data of grade II and III gliomas. They find three distinct subtypes of grade II and III gliomas characterized by discrete mutation profiles and distinct clinical behaviors.

Seishi Ogawa and colleagues report an integrated genomics analysis of more than 100 clear-cell renal carcinoma samples. They analyze whole genomes or exomes, RNA sequences and DNA methylation in ∼100 paired specimens and perform SNP array-based copy number analysis for 240 specimens. They identify new recurrently mutated pathways and new associations between DNA methylation, mutations, gene expression and copy number profiles.

Shigeru Chiba and colleagues report exome sequencing of angioimmunoblastic T cell lymphoma (AITL) and other peripheral T cell lymphomas and identify a recurrent somatic RHOA mutation encoding a p.Gly17Val alteration in 68% of AITL samples.

Chronic myelomonocytic leukaemia is treated with agents that modify DNA methylation but whether they have direct cytotoxic effects is unclear. Here, the authors show that cells from treated patients show marked methylation changes without altered somatic mutation burden, suggesting that cytotoxicity is not a major factor in therapeutic efficacy.

Excitatory spiny stellate neurons in the somatosensory cortex are shaped by innervating thalamic inputs and unique expression of genes. Here, the authors show that these neurons play a crucial role in processing distinct whisker signals and forming specialized circuits for sensory perception.

Whole-genome sequencing of haematopoietic colonies from human fetuses reveals the somatic mutations acquired by individual progenitors, which are used as barcodes to construct a phylogenetic tree of blood development.

Cardiomyocytes (CMs) derived from human induced pluripotent stem cells (hiPSCs) suffer from limited maturation. Here the authors identify ERRγ agonist as a factor that enhances cardiac morphological, metabolic, contractile and electrical maturation of hiPSC-derived CMs with T-tubule formation.