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Here Iliev et al. review the interactions between the microbiota and the mucosal immune system from infancy to adulthood, highlighting the impact on health and disease.

Liver x receptors (LXRs) regulate lipid metabolism in response to changing cholesterol levels. Here, the authors show that inactivation of LXR signaling leads to the rapid development of metabolic dysfunction-associated steatohepatitis (MASH).

Structural variants in more than 17,000 human genomes are mapped and characterized using whole-genome sequencing, showing how this type of variation contributes to rare deleterious coding and noncoding alleles.

The US COVID-19 Scenario Modeling Hub produced medium to long term projections based on different epidemic scenarios. In this study, the authors evaluate 14 rounds of projections by comparing them to the epidemic trajectories that occurred, and discuss lessons learned for future similar projects.

Phenotype of cells in the infusion product as well at specific post-infusion time points has been associated with clinical response to CD19 CAR T cells. Here the authors present a single-cell multi-omics analysis of pre- and post-infusion CAR+ and CAR- T cells from patients with relapsed or refractory B-ALL or LBCL who received CD19 CAR T therapy.

A genomic constraint map for the human genome constructed using data from 76,156 human genomes from the Genome Aggregation Database shows that non-coding constrained regions are enriched for regulatory elements and variants associated with complex diseases and traits.

A strategy for inferring phase for rare variant pairs is applied to exome sequencing data for 125,748 individuals from the Genome Aggregation Database (gnomAD). This resource will aid interpretation of rare co-occurring variants in the context of recessive disease.

Tumor-associated macrophages can restrict antitumor responses. Barreira da Silva and colleagues demonstrate that the intracellular enzyme QPCTL supports recruitment of immunomodulatory macrophages to the tumor microenvironment and its targeting can enhance tumor control.

Exome-wide sequencing studies of populations in Finland identified 26 deleterious alleles associated with 64 quantitative traits that are clinically relevant to cardiovascular and metabolic diseases.

Genome-wide association studies have identified regions which confer risk of high-grade serous epithelial ovarian cancer. Here the authors use expression quantitative train locus analysis to identify candidate genes and functionally characterise them, identifying a role for HOXD9 in ovarian cancer.

Most confirmed susceptibility variants for epithelial ovarian cancer lie in non-protein-coding sequences. Here Permuth-Wey and colleagues investigate variants in 3′ untranslated regions (UTRs) and uncover a new susceptibility locus.

Paul Pharoah, Joellen Schildkraut, Thomas Sellers and colleagues report a meta-analysis of genome-wide association studies for epithelial ovarian cancer and genotyping using the iCOGS array in 18,174 cases and 26,134 controls from 43 studies from the Ovarian Cancer Association Consortium. They identify three new ovarian cancer susceptibility loci, including one specific to the serous subtype, and their integrated molecular analysis of genes and regulatory regions at these loci suggests disease mechanisms.

HNF1B is overexpressed in the clear cell subtype and epigenetically silenced in the serous subtype of ovarian cancer. Pearce and colleagues now show that genetic variants in HNF1B are differentially associated with risks of developing these two cancer subtypes, possibly through an epigenetic mechanism.

Stig Bojesen, Georgia Chenevix-Trench, Alison Dunning and colleagues report common variants at the TERT-CLPTM1L locus associated with mean telomere length measured in whole blood. They also identify associations at this locus to breast or ovarian cancer susceptibility and report functional studies in breast and ovarian cancer tissue and cell lines.

Subpopulations of cytokine-producing and myofibroblastic hepatic stellate cells, identified by single-cell RNA sequencing, protect against or promote the development of hepatocellular carcinoma via high expression of hepatocyte growth factor or type I collagen, respectively..

Mycobiota-induced IgA antibodies regulate fungal commensalism and are affected in Crohn’s disease.

This paper demonstrates that Pif1 helicase works with polymerase d to promote DNA synthesis through a migrating D-loop, a mechanism used to copy tens of kilobases during repair of chromosome breaks by break-induced replication (BIR).

De Camilli and colleagues reveal that reducing cholesterol or sphingomyelin causes formation of tubular structures resembling early endocytic intermediates at the plasma membrane. These structures recruit sphingosine kinase 1 (SPHK1). Depleting SPHK1 inhibits endocytic recycling, revealing a link between sphingosine metabolism and endocytosis.

An international consortium reports the genomic sequence for ten Drosophila species, and compares them to two other previously published Drosophila species. These data are invaluable for drawing evolutionary conclusions across an entire phylogeny of species at once.

Results for the final phase of the 1000 Genomes Project are presented including whole-genome sequencing, targeted exome sequencing, and genotyping on high-density SNP arrays for 2,504 individuals across 26 populations, providing a global reference data set to support biomedical genetics.

de Vries, Conomos, Singh and Nicholson et al. identify two additional loci associated with coronary artery calcification (ARSE and MMP16) via a genome-wide association study in 22,400 participants from multiple ancestral groups and prove that ARSE is a mediator of vascular smooth muscle cell calcification and phenotype switching.

Simon Gayther and colleagues report 3 new risk variants for mucinous ovarian carcinoma (MOC) on the basis of an analysis of 1,644 MOC cases and 21,693 controls. They confirm an eQTL association between the HOXD9 promoter and risk SNPs at 2q31.1 using chromosome conformation capture analysis and show that HOXD9 overexpression associates with neoplastic transformation.

Georgia Chenevix-Trench and colleagues report meta-analyses of genome-wide association studies identifying six loci newly associated with epithelial ovarian cancer (EOC). They also test variants at the 12 known and 6 new EOC susceptibility loci for association in BRCA1 and BRCA2 mutation carriers.

The genome of the grey short-tailed opossum Monodelphis domestica has been sequenced and analyzed, giving a first peek at a marsupial's genetic code. Of particular interest are the genetics of the immune system, which has been studied as a model for humans, and of the X chromosome for historical reasons.

Current SARS-CoV-2 vaccine recipients differ in infection history and the magnitude of their elicited antibody response. A large human cohort distinguished by these parameters are queried for effector T cell subsets, memory B cells and ability to recognize epitopes from SARS-CoV-2 variants of concern.

The International AIDS Society Towards a Cure Working Group lays out its scientific strategy to achieve a cure for HIV.

In humans, TGFβ signalling is associated with lack of response to immunotherapy in immune-excluded tumours; in mouse models of this immune phenotype, robust tumour infiltration by T cells and tumour regression are observed only when checkpoint inhibition is combined with inhibition of TGFβ signalling.