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Infant KMT2A-rearranged acute lymphoblastic leukemia is associated with poor overall survival rates. Here, the authors use WGS and WES of 36 relapsed KMT2A-rearranged ALL and AML patients and find alterations in drug response genes in ALL, which may correspond with relapse time. Longitudinal analyses of >250 samples could track residual leukemia cells, clonal drug responses, and the upcoming relapse.

Correlation between vaccine induced serological response and protection against SARS-CoV-2 omicron infection is not well understood. Authors investigate breakthrough infections in triple-vaccinated healthcare workers, to characterise correlates of protection and viral characteristics.

The authors report the results of the phase II PEMDAC clinical study testing the combination of the HDAC inhibitor entinostat with the anti- PD-1 antibody pembrolizumab in uveal melanoma. Low tumor burden, a wildtype BAP1 gene in the tumor or iris melanoma correlates with response and longer survival.

Following first-line therapy, patients with relapsed or refractory acute myeloid leukaemia (AML) have limited therapeutic options. Here, the authors report a phase 1b/2a study investigating bemcentinib (AXL inhibitor) as monotherapy and in combination with low-dose cytarabine (LDAC) in patients with relapsed or refractory AML.

The genetics of uveal melanoma has mainly been studied in primary tumours. In this study, the authors perform whole genome sequencing as well as immune cell profiling of biopsy samples obtained from metastatic uveal melanoma patients, providing an updated genomic landscape of these advanced lesions.

Combining different types of immune therapies might benefit certain patients. Here, the authors develop an autologous immune-humanized melanoma mouse model that allows the preclinical assessment of cancer cell–T cell interactions from each individual patient and the benefits of immunotherapies combinations.

Analyses of genome and exome sequencing data identify rare coding and structural variants associated with atrial fibrillation and highlight genetic links between atrial fibrillation and cardiomyopathies.

Adenovirus type 37 (Ad37) causes epidemic keratoconjunctivitis, a highly contagious disease for which there is no specific antiviral therapy. The receptor for Ad37 infection was previously unidentified, but known to contain sialic acid. Nilsson et al. report here that Ad37 binds to the GD1a glycan motif of the GD1a ganglioside. This finding may facilitate the development of antiviral agents targeting Ad37-associated disease.

TopBP1 plays a critical role in mitigating replication stress in cancer cells by recruiting the nuclease scaffold SLX4 to underreplicated DNA during mitosis, thereby promoting MiDAS and genome stability.

Ribosomal DNA transcription is essential for cell growth and division. Here, the authors show that EMT is accompanied by Snail binding to rDNA operons and Rictor association with nucleoli to fuel an induction of ribosome biogenesis during G1/S cell cycle arrest and inhibition of ribosome biogenesis hampers EMT, differentiates primary tumors and reduces metastasis.

Genome-wide association analyses identify 93 risk loci for venous thromboembolism (VTE). A polygenic score derived from these results identifies individuals at increased VTE risk equivalent to monogenic forms of the disease.

Medin promotes the formation of vascular aggregates with amyloid-β in mouse models and in human patients with Alzheimer’s disease, and is associated with vascular defects and cognitive decline.

Fat distribution is associated with cardiometabolic disease, although it has been less well studied than overall obesity. In a multiancestry exome-sequencing study, the authors identified predicted loss-of-function mutations in INHBE associated with favorable fat distribution and protection from type 2 diabetes.

The authors investigated associations of brain-derived-tau (BD-tau) with Aβ pathology, changes in cognition and MRI signatures. Staging Aβ-pathology according to neurodegeneration, using BD-tau, identifies individuals at risk of near-term cognitive decline and atrophy.

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.

Glycan structure, attachment site and the glycoprotein from which it came can be identified with a method to enrich for glycoproteins from complex biological samples, digest them on a bead and release the glycopeptides for mass spectrometry analysis.

Endosomal escape and subsequent cytosolic delivery of siRNA therapeutics is inefficient, and quantification is difficult. Here the authors report a confocal microscopy-based method to quantify cytosolic delivery of fluorescently labelled siRNA during lipid-mediated delivery.

A multi-ancestry genome-wide association study of liver cirrhosis and its associated endophenotypes identifies and validates 14 risk variants. Integrative common and rare variant analyses provide insights into the genetic architecture of liver cirrhosis.

The oligodendrocyte lineage is known for its transcriptional heterogeneity, but the functional consequences of this are unclear. Here, the authors show that distinct populations of mature oligodendrocytes have spatial preferences in the brain and spinal cord and show different responses to spinal cord injury.

The app-based COVID Symptom Study was launched in Sweden in April 2020 to contribute to real-time COVID-19 surveillance using daily symptom reports from study participants. Here, the authors show how syndromic surveillance can be used to estimate regional COVID-19 prevalence and to predict later COVID-19 hospital admissions.

The tau protein is theorized to spread transneuronally in Alzheimers disease, though this theory remains unproven in humans. Our simulations of epidemic-like protein spreading across human brain networks support this theory, and suggest the spreading dynamics are modified by β-amyloid

Mass spectrometry imaging with fluoromethylpyridinium-based reactive matrices allows mapping of neurotransmitters at high resolution and at a low limit of detection. The approach is applied to rat, macaque and human brain tissue samples for probing Parkinson’s disease-related changes.

The dynamics of liquid water is rich due to its complex, highly disordered hydrogen-bond network, which hasn’t been fully understood. Perakis et al. measure water dynamics at sub-100 fs and show that it cannot be described by simple thermal motion due to the build-up of tetrahedral structures upon supercooling.

Common genetic variants in structural proteins contribute to risk of atrial fibrillation (AF). Here, using whole-exome sequencing, the authors identify rare truncating variants in TTN that associate with familial and early-onset AF and show defects in cardiac sarcomere assembly in ttn.2-mutant zebrafish.

In order to find a general treatment for cancer, this study found that MTH1 activity is essential for the survival of transformed cells, and isolated two small-molecule inhibitors of MTH1, TH287 and TH588 — in the presence of these inhibitors, damaged nucleotides are incorporated into DNA only in cancer cells, causing cytotoxicity and eliciting a beneficial response in patient-derived mouse xenograft models.

Resistance to ERK signaling inhibitors in BRAF^V600E-mutant melanomas and lung cancers is achieved by parallel convergent mechanisms, including amplification of the mutant allele in extrachromosomal elements, that allow tumors to adapt while maintaining their intratumor heterogeneity. Intermittent treatment with a combination of RAF, MEK and ERK inhibitors imposes a higher selective pressure than sequential therapy and produces the strongest antitumor effects while minimizing toxicity. These findings warrant evaluating the effectiveness of this combinatorial regimen in patients, to improve treatment responses and delay the emergence of drug resistance.

This analysis presents the results of a community-based evaluation of existing software for large-scale glycopeptide data analysis.

Neocortical resident microglia are long-lived cells. Füger et al. report that approximately half of these cells survive for the entire lifespan of a mouse. While microglial proliferation under homeostatic conditions is low, proliferation is increased in a mouse model of Alzheimer's disease.

Sountoulidis et al. provide a spatial gene expression atlas of human embryonic lung during the first trimester of gestation and identify 83 cell identities corresponding to stable cell types or transitional states.

Human chromosomes are captured along microtubule walls and then tethered to microtubule-ends through a multi-step end-on conversion process. Here the authors show that Aurora-B regulates end-on conversion in human cells and establish a late role for Astrin-SKAP complex in the end-on conversion process.

Establishing the relative transmissibility of emerging variants of SARS-CoV-2 is key for pandemic management. Here, the authors use full-population administrative data from Denmark linked to PCR test results and estimate that the Alpha variant was ~60% higher than other strains circulating in early 2021.

Transdifferentiation between group 1 and group 3 innate lymphoid cells (ILCs) has been observed in the gut. Spits and colleagues now show lung ILC2s are able to convert into ILC1s in an IL-12-dependent manner.