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How age affect the immune response to malaria is not fully understood. Here, the authors characterise the transcriptome and serum inflammatory cytokines in children and adults in response to malaria, showing that there is an increase of inflammatory chemokine and cellular responses in adults compared to children.

A small-molecule iron mobilizer, FeM-1269, minimally higher-order aggregates in aqueous media and effectively mobilizes iron across a range of concentrations. FeM-1269-promoted iron mobilization restores physiology in animals at well-tolerated doses.

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.

To investigate genomic diversity within tumours, a new type of whole-genome and exome single cell sequencing has been developed using G2/M nuclei; the technique was used to sequence single nuclei from an oestrogen-positive breast cancer and a triple-negative ductal carcinoma—aneuploidy rearrangements emerged as early events in tumour formation and then point mutations evolved gradually over time.

Paul Boutros, Robert Bristow and colleagues report a molecular analysis of the spatial heterogeneity of clinically localized, multifocal prostate cancer. They find that multifocal tumors are highly heterogeneous, and they identify a novel recurrent amplification of MYCL1.

Here the authors conduct a multi-ancestry meta-analysis of telomere length, used diverse approaches to identify genes underlying association signals, and experimentally validated POP5 and KBTBD6 as regulators of telomere length in human cells.

Here, the authors identify mechanistic differences in the dependence on co-transcription factors between orthologous TFs from two related yeast species, S. cerevisiae and C. glabrata. The investigation into intrinsically disordered regions sheds light on the role of autoinhibition in the reliance on co-TFs.

This single nucleus-targeted sequencing approach incorporates multiplexing and targeted capture for efficient high-throughput detection of genome variants. The protocol will be particularly useful for studying rare cells and complex cell populations.

Genomic analyses of localized, non-indolent prostate cancer identify recurrent aberrations that can predict relapse, and also highlight differences between early prostate cancer and metastatic, castration-resistant disease.

Although rare, antibodies against the receptor-binding domain of SARS-CoV-2 that showed potent antiviral activity were obtained from all tested convalescent individuals, suggesting that a vaccine designed to elicit such antibodies could be broadly effective.

Primaquine treatment for breastfeeding mothers is currently not recommended. Here, the authors develop a pharmacokinetic model to predict drug exposure of infants and show that ingesting breastmilk from mothers treated with primaquine results in <1% of maternal drug exposure. This suggests that primaquine should not be restricted in post-neonatal breastfeeding women as standard doses are unlikely to cause adverse events in infants.

It is essential to understand heterogeneity and evolution at different omics levels in oesophageal squamous cell carcinoma (ESCC). Here, the authors use multi-omics to analyse heterogeneity and evolution in ESCC patient samples, and characterise the levels of immune infiltration as well as selective pressure from the tumour microenvironment.

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.

A database of known drug-gene interactions, with information derived from many public sources, allows the identification of genes that are currently targeted by a drug and the membership of genes in a category, such as kinase genes, that have a high potential for drug development.

The One Thousand Plant Transcriptomes Initiative provides a robust phylogenomic framework for examining green plant evolution that comprises the transcriptomes and genomes of diverse species of green plants.

A new phylogenomic tree for butterflies is constructed using 391 genes from 2,300 species, representing 92% of genera. It suggests that butterflies originated around 100 million years ago in what is now the Americas and originally fed on Fabaceae.

Nicholas Navin and colleagues use highly multiplexed single-nucleus sequencing to investigate DNA copy number evolution in patients with triple-negative breast cancer. Their data suggest that most copy number alterations are acquired at the earliest stages of tumor evolution in short punctuated bursts, followed by stable clonal expansions that form the tumor mass.

Reconstructing full-length transcripts from high-throughput RNA sequencing data is difficult without a reference genome sequence. Grabherr et al. describe Trinity, an algorithm for assembling full-length transcripts from short reads without first mapping the reads to a genome sequence.

Potencies of HIV broadly neutralizing antibodies are usually defined by theirin vitro IC₅₀ and IC₈₀ values, but much higher levels will be required for successful immunotherapies. Here, Webb et al. predict antibody potency at therapeutic levels by analyzing dose–response curve slopes, which correlate with epitope class.

Transplantation of mouse-induced pluripotent stem cells (iPSCs), but not of iPSC-derived terminally differentiated cells, triggers a T-cell-dependent immune response. Here the authors show that iPSC-derived endothelial cells are accepted by self-tolerance mechanisms similar to autologous endothelial cells.

Single cell RNA sequencing is a powerful tool for understanding cellular diversity but is limited by cost, throughput and sample preparation. Here the authors use nanogrid technology with integrated imaging to sequence thousands of cancer nuclei in parallel from fresh or frozen tissue.

Monovar efficiently detects single-nucleotide variants in single-cell DNA sequence data with high sensitivity and specificity.

The relative importance of the mechanisms underlying species radiation remains unclear. Here, the authors combine reference genome assembly and population genetics analyses to show that neutral forces have contributed to the radiation of the most species-rich tree genus Syzygium.

A survey of T cell repertoire evolution in the tumors, healthy tissue and blood of patients with early-stage untreated lung cancer offers an opportunity to monitor and identify neoantigen-specific T cells for personalized immunotherapy.

The ESCRT pathway is crucial for membrane remodelling in eukaryotes. Here, Hatano et al. explore the phylogeny, structure, and biochemistry of homologues of the ESCRT machinery and the associated ubiquitylation system in Asgard archaea, the closest living relatives of eukaryotes.

A microbiome genome-wide association study using three large European cohorts identified several significant study-wide and genome-wide correlations between human genetic variants and microbial traits, and used Mendelian randomization to estimate causal relationships between microbial traits and disease.

The PNUTS-PP1 complex directly binds to RNA, and interacts with polymerase II and RNA processing factors to control transcriptional elongation rates and slow polymerase II after polyadenylation sites to promote termination. Using a genome-wide CRISPR screen, Devlin et al. identify this complex as a critical suppressor of herpesvirus KSHV gene expression. They further provide evidence that PNUTS-PP1 controls elongation both downstream and upstream of polyadenylation sites on specific viral genes.

Iron overload can be either hereditary or acquired via transfusions, and current treatments include the use of iron chelators that have adverse effects in some patients. Here the authors modify siderocalin to enhance iron excretion in urine, and demonstrate therapeutic efficacy in iron overload mouse models.

Genome-wide CRISPR screens in mouse cancer cell lines are used to identify a core, conserved set of genes and pathways that govern how cancer cells evade killing by cytotoxic T lymphocytes.

There is evidence that a proportion of the polymorphisms identified by genome-wide association studies lie in enchancer regions. Here the authors use Capture Hi-C to investigate the interaction with targets in autoimmune disease, showing interactions can be long range and cell-type specific.

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.

Small cell lung cancer (SCLC) patients frequently relapse and become resistant to chemotherapy. Here, the authors analyse the genomic and transcriptomic landscape of primary and relapsed SCLC patients as well as in vitro models, and discover that activation of WNT signalling can drive chemotherapy resistance.

Fragments of the atypical cadherin Fat1 accumulate in the mitochondria of vascular smooth muscle cells where they reduce respiration, leading to a regulated proliferative response to arterial injury.

Roquin is an RNA-binding protein that promotes the degradation of specific mRNAs and is crucial for the maintenance of peripheral immune tolerance. Here the authors show that, in addition to its target mRNAs, Roquin can bind miR-146a and the RISC component Ago2 to control homeostasis of both RNA species.

SeqControl uses 15 quality metrics of high-throughput sequencing experiments to predict how much sequencing is needed to reach a desired depth of coverage.

Patterns of amino acid conservation have been used to guide the interpretation of the disease-causing potential of genetic variants in patients; now, an appreciable fraction of pathogenic alleles are shown to be fixed in the genomes of other species, suggesting that the genomic context has an important role in allele pathogenicity.

Rapid, multiplex identification of pathogens and disease-associated mutations is possible with a new semiconductor biochip.

Thyroid dysfunction is involved in many diseases. Here, the authors provide insights into the genetics and biological pathways influencing important thyroid function parameters, showing potential causal effects on many clinical outcomes.

Salmonella mutants with reduced ability to colonize the mouse gut and cause disease are selected for by vaccine-induced intestinal antibody responses in mice.

Seasonal malaria chemoprevention provides substantial benefit for young children, but resistance to used drugs will likely develop. Here, Chotsiri et al. evaluate the use of dihydroartemisinin-piperaquine as a regimen in 179 children, and population-based simulations suggest that small children would benefit from a higher and extended dosage.

Malaria parasites must produce gametocytes for transmission to the mosquito vector, although the molecular mechanisms underlying commitment to gametocyte production remain unclear; here this process is found to be controlled by PbAP2-G, a member of the ApiAP2 family of DNA-binding proteins, in the rodent-infecting Plasmodium berghei parasite.

The Red Queen hypothesis predicts that coevolution should increase the rate of evolution at the molecular level. Here, genome sequencing in an experimental phage–bacteria system is used to show that this is true, but the effect is concentrated on specific loci, and also that coevolution drives greater diversification of phage populations.

Repetitive sequences and chromatin accessibility can confound scoring of chromatin immunoprecipitation data generated by high–throughput sequencing. Using data sets they produce for human RNA polymerase II and the transcription factor STAT1, Rozowsky et al. compensate for these biases by correcting for 'mappability' and normalizing the data against an input–DNA control.

Micro Capture-C is a chromatin conformation capture method for visualizing reproducible three-dimensional contacts of regulatory regions in the genome at base-pair resolution.

Alex Kentsis and colleagues identify somatic genomic rearrangements in primary human rhabdoid tumors characterized by deletions and inversions involving PGBD5-specific signal sequences at their breakpoints. They further show that ectopic expression of PGBD5 in primary immortalized human cells is sufficient to promote cell transformation in vitro and in immunodeficient mice in vivo, thus defining PGBD5 as an oncogenic mutator and providing a plausible mechanism for site-specific DNA rearrangements in solid tumors.

IFNγ signalling has been described as a potential driver of resistance to immune checkpoint blockade (ICB) therapy. Here the authors report that PARP14 is upregulated in chronic IFNγ-treated cancer cell models and that its inhibition restores response to anti-PD-1 therapy in preclinical cancer models.

Douglas Winton and colleagues report the results of a large insertional mutagenesis screen to identify drivers of intestinal tumorigenesis in mice. The study identifies a large number of potential cancer drivers, including new modifiers of canonical Wnt signaling and components of the FGF pathway.

Recovery from cholera is characterized by a pattern of accumulation of bacterial taxa that shows similarities to the pattern of maturation of the gut microbiota in healthy children, raising the possibility that some of these taxa may be useful for ‘repair’ of the gut microbiota in individuals whose gut communities have been ‘wounded’ through a variety of insults.

Mitochondrial double-stranded RNA can induce an interferon response if released into the cytoplasm, but self-recognition is prevented by SUV3 helicase and PNPase exoribonuclease.