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Cancer genetics has benefited from the advent of next generation sequencing, yet a comparison of sequencing and analysis techniques is lacking. Here, the authors sequence a normal-tumour pair and perform data analysis at multiple institutes and highlight some of the pitfalls associated with the different methods.

An analysis of 24,202 critical cases of COVID-19 identifies potentially druggable targets in inflammatory signalling (JAK1), monocyte–macrophage activation and endothelial permeability (PDE4A), immunometabolism (SLC2A5 and AK5), and host factors required for viral entry and replication (TMPRSS2 and RAB2A).

Both rare and common variants contribute to the aetiology of complex traits such as type 2 diabetes (T2D). Here, the authors examine the effect of coding variation on glycaemic traits and T2D, and identify low-frequency variation in GLP1Rsignificantly associated with these traits.

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.

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.

A pangenome analysis of 76 wild and domesticated barley accessions in combination with short-read sequence data of 1,315 barley genotypes indicates that allelic diversity at structurally complex loci may have helped crop plants to adapt to agricultural ecosystems.

The largest harmonized proteomic dataset of plasma, serum and cerebrospinal fluid samples across major neurodegenerative diseases reveals both disease-specific and transdiagnostic proteomic signatures, including a robust plasma profile associated with the APOEε4 genotype.

Individual SNPs have small effects on anthropometric traits, yet the impact of CNVs has remained largely unknown. Here, Kutalik and co-workers perform a large-scale genome-wide meta-analysis of structural variation and find rare CNVs associated with height, weight and BMI with large effect sizes.

Whole-genome sequencing, transcriptome-wide association and fine-mapping analyses in over 7,000 individuals with critical COVID-19 are used to identify 16 independent variants that are associated with severe illness in COVID-19.

We quantify mitochondrial DNA copy number and heteroplasmy levels and study their association with nuclear genetic loci in population-scale biobanks.

SAVANA is a tool to detect somatic structural variants and copy number aberrations using long-read sequencing data, offering high sensitivity, specificity and compatibility with or without germline controls.

The decades-old limit on how long human embryos can be grown in culture is under debate. A new road map outlines how to extend the length of culture responsibly.

On the basis of data from >329,000 migratory birds, this study presents multispecies migratory connectivity as a parameter representing exposure to global change and shows that connections between breeding regions in Canada and non-breeding regions in South America are at greatest risk from global change.

This genome-wide association study identifies four novel risk loci for testicular germ cell tumour, and provides functional correlation between a disease-associated variant and gene expression in patient samples for one of the identified loci.

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.

Duarte et al. report that common genetic variants linked to psychiatric disorders influence the regulation of ancient retroviruses integrated into the genome. This suggests ancient viruses acquired millions of years ago may have shaped modern human brain function.

MORC2, a chromatin remodeler involved in epigenetic silencing and DNA repair, is linked to cancer and neurological disorders when dysregulated. Here, the authors show that MORC2 binds DNA at multiple sites, clamps onto it, and induces compaction, a process regulated by its phosphorylation.

The heterogeneity of whole-exome sequencing (WES) data generation methods presents a challenge to joint analysis. Here, the authors present a bioinformatics strategy to generate high-quality data from processing diversely generated WES samples, as applied in the Alzheimer’s Disease Sequencing Project.

A trans-ancestry meta-analysis of GWAS of glycemic traits in up to 281,416 individuals identifies 99 novel loci, of which one quarter was found due to the multi-ancestry approach, which also improves fine-mapping of credible variant sets.

A genome-wide association meta-analysis study of blood lipid levels in roughly 1.6 million individuals demonstrates the gain of power attained when diverse ancestries are included to improve fine-mapping and polygenic score generation, with gains in locus discovery related to sample size.

When interfaced with a current-carrying heavy metal, spin orbit effects can generate a torque on the magnetization of a ferromagnet, understood as a bulk effect. Here, the authors show evidence of an interfacial contribution to such spin orbit torque in O-doped W/CoFeB thin film systems.

Here, Zerio et al. use cryo-electron microscopy to show how the helicase domain of DNA polymerase θ aligns broken DNA strands by matching short sequences, a process linked to cancer. These findings may guide future therapies targeting error-prone DNA repair.

A genome-wide association study of critically ill patients with COVID-19 identifies genetic signals that relate to important host antiviral defence mechanisms and mediators of inflammatory organ damage that may be targeted by repurposing drug treatments.

Chronic infection with SARS-CoV-2 leads to the emergence of viral variants that show reduced susceptibility to neutralizing antibodies in an immunosuppressed individual treated with convalescent plasma.

Safely opening university campuses has been a major challenge during the COVID-19 pandemic. Here, the authors describe a program of public health measures employed at a university in the United States which, combined with other non-pharmaceutical interventions, allowed the university to stay open in fall 2020 with limited evidence of transmission.

An exciting genome-wide association study in the British population for seven common diseases. This analysis confirms previously identified loci and provides strong evidence for many novel disease susceptibility loci.

Trans-ethnic analyses of exome array data identify new risk loci for type 2 diabetes. Fine-mapping analyses using genome-wide association data show that the index coding variants represent the likely causal variants at only a subset of these loci.

Timothy Spector, Mario Falchi and colleagues report a genome-wide association study for development of cutaneous nevi, the strongest known risk factor for cutaneous melanoma. They report two loci associated with nevus count, and show these loci are also associated with susceptibility to melanoma.

A novel antiviral targeting the SARS-CoV-2 PLpro protease shows strong efficacy in a mouse model, preventing lung pathology and reducing brain dysfunction. The study provides proof-of-principle that PLpro inhibition may be a viable strategy for preventing and treating long COVID.

Measuring acoustic oscillations in 27 stars within the M67 cluster presents evidence of a rapidly evolving convective zone as stars evolve from subgiants to red giants.

Bacteria can use different mechanisms to become resistant to the same antibiotic class. Here, the authors study bacterial strains that express genes conferring tetracycline resistance via different mechanisms, and find that each mechanism is preferentially selected for by specific tetracycline generations.

A general reinforcement-learning algorithm, called Dreamer, outperforms specialized expert algorithms across diverse tasks by learning a model of the environment and improving its behaviour by imagining future scenarios.

Knock-in mice conditionally or constitutively expressing Cas12 variants enable a wide range of ex vivo and in vivo applications requiring multiplexed genome engineering.

Malignant cells with mesenchymal features display increased chromatin accessibility, particularly in the pericentromeric and centromeric regions, in turn resulting in delayed mitosis and catastrophic cell division.

The North Atlantic region experiences climate variability on multidecadal timescales. An analysis of a tree-ring network shows this variability can be attributed to both internal and external forcing over the past 1,200 years.

Genotype and exome sequencing of 150,000 participants and whole-genome sequencing of 9,950 selected individuals recruited into the Mexico City Prospective Study constitute a valuable, publicly available resource of non-European sequencing data.

Whole-genome sequencing analysis of individuals with primary immunodeficiency identifies new candidate disease-associated genes and shows how the interplay between genetic variants can explain the variable penetrance and complexity of the disease.

Molecular diagnostics for tuberculosis have focused on predicting drug susceptibilities in a binary manner (i.e., strains are either susceptible or resistant). Here, CRyPTIC Consortium researchers use whole genome sequencing and a quantitative assay to identify associations between genomic mutations and minimum inhibitory concentrations in over 15,000 Mycobacterium tuberculosis clinical isolates.

Timothy Radstake and Maureen Mayes and colleagues report results of a genome-wide association study of systemic sclerosis. They identify a new susceptibility locus at CD247.

Endometrial cancer is the most common invasive gynaecological cancer in developed countries. Here a meta-analysis identifies an additional nine novel endometrial cancer risk loci and eQTL analysis reveals risk variants associate with reduced expression of negative regulators of oncogenic signal transduction proteins.

Oncogenic gene fusions are frequent in childhood cancers but remain poorly understood and untargeted. Here, the authors identify 272 oncogenic fusions in transcriptomics data from 5190 childhood cancer patients, revealing their possible etiologies, their links with tumor progression and evolution, and their potential as therapeutic targets.

Ruth Loos and colleagues report results of a large genome-wide association study for body mass index. They identify 18 new loci associated with this trait, some of which map near key hypothalamic regulators of energy balance.

Whole-genome sequencing of matched serial tumours from patients identifies two key mutagenic factors (APOBEC3 and chemotherapy) and extrachromosomal DNA-forming structural variants that drive treatment resistance in urothelial cancer.

A secure framework that harmonizes storage and querying of clinical and genetic data using blockchain technology was developed to support combined genotype–phenotype queries, improving transparency into how and when health information is used.

Analyses of in vivo models, cell lines and patient-derived samples show that apolipoprotein B mRNA-editing catalytic subunit 3B (APOBEC3B) not only restrains lung tumor initiation but also that its upregulation is associated with resistance to targeted therapies. This study highlights the complex and context-dependent role of APOBEC3B in lung cancer.

The genetic factors that predispose individuals to familial colorectal cancer are poorly understood. In this study, the authors use whole exome sequencing of 1,006 patients and 1,609 healthy controls and show it is unlikely that further major high-penetrance susceptibility genes exist.

The GEMINI consortium sequenced 1,000 cases of idiopathic male infertility and identified a plausible Mendelian cause in 20% of cases. The infertility genes can be grouped by expression pattern, facilitating their interpretation and follow-up.