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Here, the authors apply genome-scale metabolic network reconstructions to metagenomic data obtained from human vaginal swabs to identify bacterial vaginosis-associated bacterial metabolic interactions, and validate in vitro microbial metabolites implicated in host estrogen receptor binding.

A pangenome of the Cannabis genus including 193 genomes demonstrates high variability in most of the genome but low diversity in cannabinoid synthesis genes and provides a resource for future genetic studies and crop optimization.

A pan-cancer analysis of genomic data from matched primary and metastatic tumors from 3,732 patients shows that increased genomic complexity and alterations that facilitate immune evasion are associated with disease progression.

A systematic gene deletion screen targeting all predicted transmembrane transporters of the protozoan parasite Leishmania identified forty mutants that had a significant loss of fitness in macrophage and mouse infections. Loss of the V-type H⁺ ATPase was particularly deleterious in vivo.

Integrated single-cell transcriptomic and genetic characterization of 121 adult glioblastomas identifies heterogeneity at cell type, cell state and baseline expression program levels associated with specific mutations that form three stereotypical ecosystems.

Comparison of paired primary and recurrent glioblastomas at the single-cell transcriptomic level describes molecular and cellular trajectories associated with tumor recurrence, highlighting extensive heterogeneity and microenvironmental co-evolution.

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).

Dzando et al. identify locally relevant frailty thresholds for older people in Sub-Saharan Africa through Receiver Operating Characteristic analysis and random-effects meta-analysis. Findings demonstrate variability in population level thresholds with a pooled threshold of 0.29 demonstrating good sensitivity and specificity across the populations.

The authors present a characterization of complex X-linked lncRNA loci with sex- and allele-specific epigenetic signatures that serve as a platform for the largest chromatin structures in mammals, thereby elucidating diverse phenotypes and combinatorial effects on autosomes.

Tumour-informed ctDNA is a sensitive potential biomarker for treatment response in breast cancer. Here, the authors use longitudinal sampling to predict disease recurrence during neoadjuvant and adjuvant treatment.

Nursing homes are high-risk settings for transmission of infections, but risks associated with specific activities are not well understood. Here, the authors investigate transmission dynamics of multi-resistant organisms in nursing homes in the United States with a focus on out-of-room, interactive visits.

Centromere fragility can drive tumourigenesis, so protective mechanisms are important. Here, the authors suggest that the PBAF chromatin remodelling complex, which is frequently misregulated in cancer, helps to maintain the integrity of centromeres.

In this phase 1 trial, patients with locally advanced or metastatic solid tumors were treated with the individualized mRNA neoantigen-specific immunotherapy (iNeST) autogene cevumeran alone or in combination with the anti-PD-L1 agent atezolizumab, showing long-lasting neoantigen-specific immune responses and preliminary clinical activity, supporting further development of this therapeutic approach.

The ability to vaccinate against multiple related pathogens is a significant advantage. Here, the authors report on quartets of linked receptor-binding domains attached to designed nanocages using SpyTag/SpyCatcher links, demonstrating effective vaccination against similar viruses as well as the variant of concern.

The opening mechanism of the SARS-CoV-2 spike protein has been studied by integrating computational and experimental data. Combining weighted ensemble molecular dynamics simulations, biolayer interferometry and ManifoldEM analysis of cryo-EM data revealed that the glycan at N343 plays a gating role in the opening mechanism of the SARS-CoV-2 spike protein.

In cancer, the impact on cellular fitness of copy-number gains affecting collaterally-amplified genes remains poorly understood compared to oncogenes. Here, the authors integrate genomic data from tumours and cell lines and identify a class of ‘Amplification-Related Gain Of Sensitivity’ (ARGOS) genes, with potential therapeutic applications.

CRISPR-CasRx effectively reduces ALS- and FTD-causing C9orf72 sense and antisense repeat derived RNAs and proteins in cell lines, patient iPSC-neurons and two independent mouse models of C9orf72 repeat expansion.

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.

Increased IL-13 drives increased bacterial dissemination and mortality following Acinetobacter baumannii lung infection of zinc-deficient mice and can be countered by anti-IL-13 antibody therapy.

Lillian Musila highlights a paper by Quick et al., which reported the use of portable nanopore sequencing for on-site, real-time genomic surveillance during the 2014–2016 Ebola virus epidemic.

Although circulating tumour DNA (ctDNA) can predict immune checkpoint blockade (ICB) responses, its association with tumour biomarkers remains unknown. Here, the authors use ctDNA to inform exome and transcriptome profiling of >100 patients with 30 cancer types on a single clinical ICB trial and identify tumour microenvironment features associated with response.

Researchers developed an accurate model to analyse bivalent antibody binding. By analysing many SARS-CoV-2-specific antibodies, they found that their molecular reach can predict their neutralisation potency.

Analysis of human tumor datasets shows that all features that appear significantly associated with immunotherapy response and survival may be collapsed into five latent factors: tumor mutation burden, T cell effective infiltration, TGF-β activity in the microenvironment, prior treatment and tumor proliferative potential.

Haplotype reconstruction of distant genetic variants is problematic in short-read sequencing. Here, the authors describe HapTree-X, a probabilistic framework that uses differential allele-specific expression to better reconstruct paternal haplotypes from diploid and polyploid genomes.

Siu and colleagues use a bespoke ctDNA assay and show predictive utility of longitudinal ctDNA analysis in a phase II clinical trial of patients receiving pembrolizumab that included multiple solid tumor types.

Functional materials that act as bio-sensing media when interfaced with complex bio-matter are attractive for health sciences and bio-engineering. Here, the authors report room temperature enzyme-mediated spontaneous hydrogen transfer between a perovskite quantum material and glucose reactions.

Quantifying intact proviruses is key to understanding decreases in HIV reservoirs but results can differ depending on the method. To balance sensitivity and specificity of two assays, the authors use mathematical models and measurements of intact and defective proviruses to assess how misclassification can impact estimates of natural and therapeutic reservoir reduction.

Loading of antigenic peptides onto MHC-I is essential for adaptive immunity and requires the protein Tapasin. Here, the authors demonstrate that Tapasin levels are controlled by the RNF185/MBRL ERAD complex and that this process regulates MHC-I surface expression.

A strategic dialogue on ‘gender justice in the HIV response’ held at the 25th International AIDS Conference highlighted how bias and discrimination against women and girls in all their diversities disadvantages them in the HIV response. Ending AIDS requires increased participation and leadership by diverse women at all levels of the HIV response.

Adenosine-to-inosine editing is a form of RNA modification observed in the human brain transcriptome. Here the authors question the accuracy of utilizing postmortem samples to reflect the RNA biology of living brains. This is due to significant differences in adenosine-to-inosine editing between living and postmortem brain tissues, with most sites exhibiting higher editing levels postmortem.