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When Harriet Wallberg-Henriksson began her medical career, she never expected to be a trailblazer for either women or young scientists. But now she is the first female president of the Karolinska Institute in Stockholm, Sweden, she finds that she is working hard on behalf of both groups. She hopes to raise the proportion of women professors at the institute from 15% to 40%, and has set up a junior faculty programme to help young scientists jumpstart their career, which includes a mentoring component just for women scientists. But there is still more to be done. Wallberg-Henriksson discusses progress and things to come with Naturejobs editor Paul Smaglik. Comments have been edited for accuracy, conciseness and clarity.

This work introduces a pedigree-derived benchmark for single-nucleotide variants, indels, structural variants and tandem repeats, offering a variant map to validate sequencing workflows or to support the development and evaluation of new variant callers.

Using data from the CoVPN 3008 study, the authors show that the neutralizing antibody correlate of risk holds in people living with HIV. However, the nAb correlate was weaker and shorter-lived in a vaccine-immunity versus hybrid-immunity population.

Analysis of more than 95% of each diploid human genome of a four-generation, twenty-eight-member family using five complementary short-read and long-read sequencing technologies provides a truth set to understand the most fundamental processes underlying human genetic variation.

Feuerer and colleagues use multiomic analyses to identify DNA methylation, chromatin accessibility and gene expression programs that govern the tissue adaptation of human skin T_reg cells.

This study analysed genetic data of soil-transmitted helminths from 27 countries, revealing diversity impacting molecular test accuracy and highlighting the need to adapt diagnostics for effective STH surveillance.

A set of tools maps tandem repeats across complete genomes.

Circulating tumour DNA profiling in early-stage non-small-cell lung cancer can be used to track single-nucleotide variants in plasma to predict lung cancer relapse and identify tumour subclones involved in the metastatic process.

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).

Meta-omic analyses are commonly used for large-scale studies of microbial eukaryotes. Here, Krinos et al. explore the potential pitfalls of common approaches to taxonomic annotation of protistan meta-omic datasets, highlighting the importance of database completeness and curation and proposing that precise taxonomic annotation of meta-omic data is a clustering problem rather than a feasible alignment problem.

Using an autonomous underwater vehicle, this study presents an integrated biogeochemical and multiomic analysis of microbial eukaryotes from the North Atlantic Ocean. The work highlights diverse communities that shift through depth zones, with signatures of nutrient biomarkers changing across a coastal-offshore spatial gradient.

Some antiseizure medications including valporate are associated with neurodevelopmental conditions in children exposed in utero but evidence is less clear for other drugs. Here the authors investigate associations between antiseizure medication use in pregnancy and neurodevelopmental conditions using electronic health record data from the UK and Sweden.

A global network of researchers was formed to investigate the role of human genetics in SARS-CoV-2 infection and COVID-19 severity; this paper reports 13 genome-wide significant loci and potentially actionable mechanisms in response to infection.

The emRiboSeq sequencing method is used to track polymerase activity genome-wide in vivo; despite Okazaki fragment processing, DNA synthesized by error-prone polymerase-α (Pol-α) is retained in vivo and comprises ∼1.5% of the genome, establishing Pol-α as an important source of genomic variability and providing a mechanism for site-specific variation in nucleotide substitution rates.

Africa-specific genetic variation on chromosome 1 near CHD1L is associated with HIV replication in vivo.

A fusion of RNA-binding proteins (RBPs) to a poly(U) polymerase allows the tagging of endogenous RNAs bound by the RBPs with a U-tail that can be used to identify the bound RNA by sequencing. RNA tagging is suited to discover RNA-protein networks in vivo.

Tumor-antigen-specific CD8⁺ T cells are generally thought to help fight against cancer, but here the authors identify a subpopulation of CD8⁺ T cells that are associated with a poor clinical outcome in melanoma. Although these cells can recognize tumor antigens, they suppress cancer immunity.

Seshadri, Davis and colleagues show that individuals who do not develop an infection with Mycobacterium tuberculosis (Mtb), despite exposure to the bacteria and expansion of CD4⁺ T cell clones specific to Mtb antigens, show enrichment of T_H17 cell and T regulatory functional programs.

This Review describes tools and approaches for characterizing short tandem repeats in the human genome from whole-genome sequencing data. Furthermore, the authors discuss how these recent developments have helped to better understand the effect of short tandem repeats on human health and disease.

Whole-genome sequencing and phenotype data sharing are introduced in a national health system to streamline diagnosis and to discover coding and non-coding variants that cause rare diseases.

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.

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.

Although immune checkpoint blockade is a standard treatment for patients with malignant mesothelioma, only a minority of patients exhibit radiological response. In a phase II clinical trial (MIST4) investigating the efficacy, safety and molecular correlates of response following treatment with atezolizumab and bevacizumab, the authors demonstrate that the gut microbiota may modulate responsiveness to treatment.

There are more than 20 known melanoma susceptibility genes. Here, using a massively parallel reporter assay, the authors identify risk-associated variants that alter gene transcription, and demonstrate that expression of one such gene, MX2, leads to the promotion of melanoma in a zebrafish model.

Emerging findings identify important roles for brain lipoprotein receptors in the control of whole-body energy homoeostasis. Here Lee et al. reveal that IDOL-mediated regulation of VLDLR abundance in neurons, but not in peripheral metabolic tissues, regulates food intake and energy expenditure.

Ruth Halaban, Michael Krauthammer and colleagues report exome sequencing of 213 melanomas and identify a distinct co-mutation pattern of NF1 with known RASopathy genes. They identify novel melanoma mutations in several RASopathy genes and suggest that mutations in these genes may enhance the pathogenicity of NF1 mutation.

Viruses are partners in ecosystem ecology, yet their study has been primarily limited to laboratory models virus-host or derived from metagenomics. Here, Moniruzzamanet al. use metatranscriptomics to resolve interactions between giant viruses and single-celled eukaryotic hosts.

Recent developments in sequencing technologies have provided the opportunity to investigate the biodiversity of ecosystems. Such a metagenomic approach, combined with taxon clustering, is used here to demonstrate that the species richness of a marine community in Scotland is much greater than anticipated.

The whipworm Trichuris trichiura is a soil-transmitted helminth that causes the neglected tropical disease trichuriasis in humans. Here, the authors produce whole genome sequences of modern and ancient samples from humans and non-human primates to characterise the genomic diversity and evolution of this pathogen.

RNA sequencing data and tumour pathology observations of non-small-cell lung cancers indicate that the immune cell microenvironment exerts strong evolutionary selection pressures that shape the immune-evasion capacity of tumours.

OpenSAFELY, a new health analytics platform that includes data from over 17 million adult NHS patients in England, is used to examine factors associated with COVID-19-related death.

A comprehensive analysis of models of brain metastasis and multiple cohorts of patient samples identifies a targetable molecular mechanism underlying the resistance to whole-brain radiotherapy that can inform patient selection for personalized radiotherapy.

Haniffa and colleagues provide diagnostic aids, potential biomarkers for disease staging and therapeutic strategies for cutaneous T cell lymphoma.

Mexican Tetra cavefish have long been of interest in understanding adaptation to severe environmental change. Here the authors present a chromosome-level genome for the proxy-ancestral surface fish, and use CRISPR gene-editing to show the role of the rx3 gene in eye size.

Genome sequencing and analyses of common buckwheat, Fagopyrum esculentum, reveal the genetic architecture of heterostyly, show that southeast Tibet played a key role in the domestication and provide new genetic materials for buckwheat breeding.

Many genetic variants have been associated with human traits, but the mechanism is often unknown. Here, the authors integrate local and distal genetic associations with multi-omics datasets to provide a roadmap to understand the underlying mechanisms of GWAS variants on complex traits.

Numerous genetic variants, including those located in the non-coding regions of the genome, are known to be associated with blood cells traits. Here, Frontini and colleagues investigate their potential regulatory functions using epigenomic data and promoter long-range interactions.

Cooling electrons into the microkelvin temperature range is of interest both for practical purposes and fundamental studies, but current demonstrations are limited to small, specific devices. Here, the authors achieve sub-millikelvin temperatures in a large-area, two-dimensional electron gas.

Ruth Halaban and colleagues report exome sequences of 147 melanoma tumors. They identified a recurrent somatic activating alteration in the Rho GTPase RAC1 in sun-exposed melanomas.

Sera from vaccinated individuals and some monoclonal antibodies show a modest reduction in neutralizing activity against the B.1.1.7 variant of SARS-CoV-2; but the E484K substitution leads to a considerable loss of neutralizing activity.

G-quadruplex stabilizers, including CX-5461, exhibit synthetic lethality with loss of BRCA1/2 in preclinical models. Here the authors report the results of a phase I study of CX-5461 in patients with solid tumors enriched for DNA-repair deficiencies.

Loss of NECTIN1 is a frequent event in human melanoma and is associated with metastasis. NECTIN1 depletion modulates a switch from cell–cell adhesion to cell–matrix adhesion in response to low levels of IGF1 signaling from the microenvironment.

How biodiversity is linked to multiple ecosystem functions is not fully understood. Here, the authors show that a new mechanism, which they term the 'jack-of-all-trades' effect, best explains patterns of tree diversity and ecosystem multifunctionality in European forests.