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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).

Whole-genome sequencing of an ancient male Egyptian revealed a mixture of North African Neolithic and eastern Fertile Crescent ancestry, suggesting human migration between Egypt and Mesopotamia by the Old Kingdom period.

Iron has been shown to be necessary for the activation and differentiation of CD8⁺ T cells. Here the authors investigate changes in CD8⁺ T cell metabolism in iron limiting conditions and find that aspartate is increased yet downstream nucleotide synthesis is suppressed and addition of exogenous aspartate partially rescues T cell function.

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.

A trail-blazing astronomer, a climate revolutionary and a transplant pioneer are some of the people behind this year’s big stories.

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.

Genome-wide analyses identify 30 independent loci associated with obsessive–compulsive disorder, highlighting genetic overlap with other psychiatric disorders and implicating putative effector genes and cell types contributing to its etiology.

Some initial effects of long-term spaceflight ebbed in the months after astronaut Scott Kelly returned to Earth.

Loss-of-function mutations in tumour suppressor genes are associated with oesophageal adenocarcinoma (EAC), but the mechanisms underlying EAC development remain unclear. Here, the authors show that EACs present a high frequency of genomic catastrophes resulting in amplification of potent oncogenes.

NASA research on Mark and Scott Kelly may never get published.

The histone demethylase KDM6B is reported to be essential for neuroblastoma cell survival. Here the authors show that KDM6B regulates CDK4/6-pRB-E2F pathway through H3K27me3-dependent enhancer-promoter interactions in neuroblastoma.

Unusual study of NASA’s Scott and Mark Kelly finds gene-expression shifts during nearly a year in space.

Solid organ transplant recipients are at increased risk of infectious disease and have unique molecular pathophysiology. Here the authors use host-microbe profiling to assess SARS-CoV-2 infection and immunity in solid organ transplant recipients, showing enhanced viral abundance, impaired clearance, and increased expression of innate immunity genes.

Reducing reliance on Earth-supplied feedstocks is crucial for advancing in-space biomanufacturing. Here, the authors explored three alternative feedstocks – Martian and Lunar regolith, post-consumer polyethylene terephthalate, and fecal waste – to develop an alternative medium for cost-effective in-space lycopene biomanufacturing.

Combination of epidemiology, preclinical models and ultradeep DNA profiling of clinical cohorts unpicks the inflammatory mechanism by which air pollution promotes lung cancer

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.

The authors present results from the REACT-2 study, a series of cross-sectional community surveys during the SARS-CoV-2 pandemic in England. They measure antibodies by self-administered lateral flow tests and describe antibody positivity by time since vaccination, age, sex, co-morbidities, infection history, and vaccine type.

Multisystem inflammatory syndrome in children (MIS-C) onsets in COVID-19 patients with manifestations similar to Kawasaki disease (KD). Here the author probe the peripheral blood transcriptome of MIS-C patients to find signatures related to natural killer (NK) cell activation and CD8+ T cell exhaustion that are shared with KD patients.

Mixed responses to targeted therapy within a patient are a clinical challenge. Here the authors show that TP53 loss-of-function cooperates with whole genome doubling which increases chromosomal instability. This leads to greater cellular diversity and multiple routes of resistance, which in turn promotes mixed responses to treatment.

An investigation using various methods reports an association between adeno-associated virus 2 and paediatric hepatitis of unknown aetiology.

Diverse microbial polyphenol transformations in thawing permafrost refute the theory that these compounds stabilize soil carbon across Arctic landscapes.

Authors perform an analysis of the patient data and risk factors to evaluate unfavorable outcomes and adverse events in adults with pulmonary tuberculosis treated with a 4-month rifapentine based regimen. Low rifapentine exposure was the most clinically significant risk factor for treatment failure and tuberculosis relapse.

The advantage of living in cities compared with rural areas with respect to height and BMI in children and adolescents has generally become smaller globally from 1990 to 2020, except in sub-Saharan Africa.

Meta-analyses in up to 1.3 million individuals identify 87 rare-variant associations with blood pressure traits. On average, rare variants exhibit effects ~8 times larger than the mean effects of common variants and implicate candidate causal genes at associated regions.

Primary biliary cirrhosis is an autoimmune liver disease with poor therapeutic options. Here Cordell et al. a perform meta-analysis of European genome-wide association studies identifying six novel risk loci and a number of potential therapeutic pathways.

The role of IgG glycosylation in the immune response has been studied, but less is known about IgM glycosylation. Here the authors characterize glycosylation of SARS-CoV-2 spike specific IgM and show that it correlates with COVID-19 severity and affects complement deposition.

A conserved network of bacteria and fungi underpins cadaver decomposition despite selection effects of ___location, climate and season.

Triple-negative breast cancers (TNBCs) are a heterogeneous group of cancers with varying prognoses. Here, the authors carry out whole-genome methylation capture sequencing from TNBC samples and matched normal samples, and identify differentially methylated regions that define a potentially novel TNBC signature.

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.

Faced with a loss of crucial climate data, scientists are finding workarounds as relations with Russian partners break down.

Reference assemblies of great ape sex chromosomes show that Y chromosomes are more variable in size and sequence than X chromosomes and provide a resource for studies on human evolution and conservation genetics of non-human apes.

Openshaw and colleagues find myeloid inflammation and complement activation signatures in patients with long COVID who were previously hospitalized.

Here the authors identify 33 individuals with a dominant neurodevelopmental disorder due to heterozygous missense or loss-of-function variants in the gene encoding Densin-180, a scaffold protein present at postsynaptic sites in neurons of the central nervous system.

Post-acute sequelae of SARS-CoV-2 (PASC) is still not well understood. Here the authors provide patient reported outcomes from 590 hospitalized COVID-19 patients and show association of PASC with higher respiratory SARS-CoV-2 load and circulating antibody titers, and in some an elevation in circulating fibroblast growth factor 21.

 A transcriptomic cell-type atlas of the whole adult mouse brain with ~5,300 clusters built from single-cell and spatial transcriptomic datasets with more than eight million cells reveals remarkable cell type diversity across the brain and unique cell type characteristics of different brain regions. 

Mutations in glucocerebrosidase (GCase) cause the lysosomal storage disorder Gaucher’s disease and are the most common risk factor for Parkinson’s disease. Using a fusion protein comprising GCase and a transferrin receptor antibody fragment, the authors show that the transferrin receptor pathway can be therapeutically exploited to both pass the blood-brain barrier and efficiently target lysosomal GCase deficiency.

As phase 1 of the Earth Microbiome Project, analysis of 16S ribosomal RNA sequences from more than 27,000 environmental samples delivers a global picture of the basic structure and drivers of microbial distribution.

Bulky DNA adducts are important replication-blocking lesions. Here the authors reveal that homologous recombination at bulky adducts in mammalian cells involves post-replicative gap repair in a PrimPol dependent manner.

Correlation of microbiome features with host quality of life and depression identified specific taxa and microbial pathways in two independent, large population cohorts, identifying links between microbial neuroactive potential and depression.

Marginal zone lymphoma (MZL) is a common subtype of B-cell non-Hodgkin lymphoma. Here the authors carry out a two-stage genome-wide association study in over 8,000 Europeans and identify two new MZL risk loci at chromosome 6p, implicating the major histocompatibility complex in the disease for the first time.