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Using blood-based genome sequence data, non-genetic and genetic factors associated with control of Epstein–Barr virus during persistent infection are reported.

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.

During plant cultivation, denitrification process can release greenhouse gas nitrous oxide (N₂O) to atmosphere. Here, the authors develop a soybean–bradyrhizobial symbiosis system with enhanced capacity to reduce N₂O emissions using the incompatibility between two soybean R genes and their effector present in bradyrhizobia.

This study reveals that lysosomal dysfunction in senescent cells impairs lipid peroxidation and ferroptosis under cystine deprivation, uncovering a new mechanism of ferroptosis resistance linked to cellular senescence and providing a therapeutic strategy for age-related diseases.

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.

Hidewaki Nakagawa and colleagues report a comprehensive genome-wide mutational landscape of 300 liver cancers from Japanese individuals. They identify candidate driver mutations, including ones in noncoding regions, and structural mutations affecting the expression of nearby genes.

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.

The IKK complex activates the NF-κB pathway and can culminate in inflammation, which needs to be tightly controlled. NEMO is part of the IKK complex and, in this study, is shown to associate with the golgi-reassembly protein p47, resulting in the lysosomal degradation of NEMO and inhibition of NF-κB activation.

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.

A new method to quantify three masting components from individual tree-years has revealed that globally, masting is uncommon in tree species that depend on mutualist dispersers, with its distribution further mediated by climate and nutrient availability.

Hidewaki Nakagawa and colleagues report the whole-genome sequencing of 27 hepatocellular carcinomas. They find that chromatin regulators were mutated in approximately 50% of tumors.

There’s an emerging body of evidence to show how biological sex impacts cancer incidence, treatment and underlying biology. Here, using a large pan-cancer dataset, the authors further highlight how sex differences shape the cancer genome.

Some cancer patients first present with metastases where the location of the primary is unidentified; these are difficult to treat. In this study, using machine learning, the authors develop a method to determine the tissue of origin of a cancer based on whole sequencing data.

The characterization of 4,645 whole-genome and 19,184 exome sequences, covering most types of cancer, identifies 81 single-base substitution, doublet-base substitution and small-insertion-and-deletion mutational signatures, providing a systematic overview of the mutational processes that contribute to cancer development.

Intrahepatic cholangiocarcinoma and combined hepatocellular cholangiocarcinoma displaying biliary phenotypes are aggressive cancers. Fujimoto et al. characterize the mutational profile of chronic hepatitis and identify mutations in KRAS and IDHassociated with poor survival.

Understanding deregulation of biological pathways in cancer can provide insight into disease etiology and potential therapies. Here, as part of the PanCancer Analysis of Whole Genomes (PCAWG) consortium, the authors present pathway and network analysis of 2583 whole cancer genomes from 27 tumour types.

Analyses of 2,658 whole genomes across 38 types of cancer identify the contribution of non-coding point mutations and structural variants to driving cancer.

In somatic cells the mechanisms maintaining the chromosome ends are normally inactivated; however, cancer cells can re-activate these pathways to support continuous growth. Here, the authors characterize the telomeric landscapes across tumour types and identify genomic alterations associated with different telomere maintenance mechanisms.

With the generation of large pan-cancer whole-exome and whole-genome sequencing projects, a question remains about how comparable these datasets are. Here, using The Cancer Genome Atlas samples analysed as part of the Pan-Cancer Analysis of Whole Genomes project, the authors explore the concordance of mutations called by whole exome sequencing and whole genome sequencing techniques.

The flagship paper of the ICGC/TCGA Pan-Cancer Analysis of Whole Genomes Consortium describes the generation of the integrative analyses of 2,658 cancer whole genomes and their matching normal tissues across 38 tumour types, the structures for international data sharing and standardized analyses, and the main scientific findings from across the consortium studies.

Integrative analyses of transcriptome and whole-genome sequencing data for 1,188 tumours across 27 types of cancer are used to provide a comprehensive catalogue of RNA-level alterations in cancer.

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.

Viral pathogen load in cancer genomes is estimated through analysis of sequencing data from 2,656 tumors across 35 cancer types using multiple pathogen-detection pipelines, identifying viruses in 382 genomic and 68 transcriptome datasets.

Analysis of cancer genome sequencing data has enabled the discovery of driver mutations. Here, as part of the ICGC/TCGA Pan-Cancer Analysis of Whole Genomes (PCAWG) Consortium the authors present DriverPower, a software package that identifies coding and non-coding driver mutations within cancer whole genomes via consideration of mutational burden and functional impact evidence.

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.

An analysis of 2,954 genomes from 38 cancer subtypes identified 19,166 retrotransposition events in 35% of samples. Aberrant LINE-1 retrotranspositions can lead to the deletion of tumor-suppressor genes as well as the amplification of oncogenes.

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.

The authors present SVclone, a computational method for inferring the cancer cell fraction of structural variants from whole-genome sequencing data.

Many tumours exhibit hypoxia (low oxygen) and hypoxic tumours often respond poorly to therapy. Here, the authors quantify hypoxia in 1188 tumours from 27 cancer types, showing elevated hypoxia links to increased mutational load, directing evolutionary trajectories.

Multi-omics datasets pose major challenges to data interpretation and hypothesis generation owing to their high-dimensional molecular profiles. Here, the authors develop ActivePathways method, which uses data fusion techniques for integrative pathway analysis of multi-omics data and candidate gene discovery.

In this study the authors consider the structural variants (SVs) present within cancer cases of the ICGC/TCGA Pan-Cancer Analysis of Whole Genomes (PCAWG) Consortium. They report hundreds of genes, including known cancer-associated genes for which the nearby presence of a SV breakpoint is associated with altered expression.

Cancers evolve as they progress under differing selective pressures. Here, as part of the ICGC/TCGA Pan-Cancer Analysis of Whole Genomes (PCAWG) Consortium, the authors present the method TrackSig the estimates evolutionary trajectories of somatic mutational processes from single bulk tumour data.

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.

The authors developed an engineered FcRnimmobilized column. Analysis using the column revealed structural insights into IgG–FcRn interactions. Based on the results, a model of the IgG–FcRn complex on the membrane surface was proposed.

Live imaging and single-cell transcriptomics of mouse hair follicles reveal their development from 2D concentric zones in the placode to 3D longitudinal compartments, one of which is a stem cell compartment.

A material based on a three-dimensional –Fe–N≡C–Mo– anionic framework that hosts a Cs⁺ cation in every other pore has been shown to exhibit superionic conductivity, despite its polar crystal structure. It also exhibits second harmonic generation (SHG)—usually observed in insulators—and its ionic conductivity was reversibly altered under light irradiation.

Mediator subunit MED26 was shown to help recruit Super Elongation Complex (SEC) or Little Elongation Complex (LEC) to control the expression of certain genes. Here, the authors provide evidence that MED26 recruits LEC to regulate transcription termination of non-polyadenylated genes, including snRNA and replication-dependent histone (RDH) genes at Cajal bodies.

Antiviral immune responses involve clustering of plasmacytoid dendritic cells (pDC) in response to endosomal TLR7-mediated sensing of viral RNA. Here the authors show the GTPase Arl8b controls translocation of TLR7⁺ endosomes to the periphery of the cell via microtubule interactions, thus enabling pDC clustering and type I interferon production.

Structural variations disrupting the 3′ region of PD-L1 are shown to aid immune evasion in a number of human cancers, including adult T-cell leukaemia/lymphoma, and in a mouse tumour model, CRISPR/Cas9-mediated deletion of the 3'-UTR of Pd-l1 is also shown to result in immune escape, suggesting that PD-L1 3′-UTR disruption could provide a diagnostic marker to identify patients who will benefit from anti-PD-1/PD-L1 therapy.

A total of 1074 patients with a history of ischemic stroke enrolled in The Recurrent Stroke Prevention Clinical Outcome (RESPECT) Study were assigned to intensive blood pressure (BP) control group (blood pressure < 120/80 mmHg) or standard blood pressure control group (blood pressure < 140/90 mmHg) and were followed up for a mean of 3.9 years. Seventy-eight first recurrent strokes occurred, including 70 ischemic stroke and 8 intracerebral hemorrhage. Intensive treatment did not change annual risk of ischemic stroke (1.74% vs. 1.75%, P = 0.999), but markedly reduced risk of hemorrhagic stroke (0.00% vs. 0.39%, P = 0.005). Beneficial effect of intensive BP control were observed for risk of hemorrhagic stroke in the patients with a history of ischemic stroke.

Analysis of whole-genome sequencing data across 2,658 tumors spanning 38 cancer types shows that chromothripsis is pervasive, with a frequency of more than 50% in several cancer types, contributing to oncogene amplification, gene inactivation and cancer genome evolution.

Analysis of mitochondrial genomes (mtDNA) by using whole-genome sequencing data from 2,658 cancer samples across 38 cancer types identifies hypermutated mtDNA cases, frequent somatic nuclear transfer of mtDNA and high variability of mtDNA copy number in many cancers.

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