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Despite improving therapeutic options, the prognosis for patients with metastatic castration-resistance prostate cancer (mCRPC) remains poor. Here, the authors identify MCL1 copy number alterations as a prognostic and predictive biomarker, demonstrating its therapeutic potential as a drug target, either alone or in combination, in patients with mCRPC.

Chronic care manages long-term, progressive conditions, while acute care handles short-term ones. Here, authors show chronic conditions account for most of the global health burden, with 68% of DALYs and 93% of YLDs attributed to chronic care needs.

Polygenic risk scores can help identify individuals at higher risk of type 2 diabetes. Here, the authors characterise a multi-ancestry score across nearly 900,000 people, showing that its predictive value depends on demographic and clinical context and extends to related traits and complications.

The recent developments in artificial intelligence (AI) have created both intrigue and apprehension in the world of research. In this Viewpoint, we asked 12 experts in the field of metabolism to share their — differing — opinions on the use of AI in pre-clinical and clinical metabolic research.

Here the authors perform a trans expression quantitative trait locus meta-analysis study of over 3,700 people and link a USP18 variant to expression of 50 inflammation genes and lupus risk, highlighting how genetic regulation of immune responses drives autoimmune disease and informs new therapies.

Genotype-phenotype data from over 450,000 individuals was analyzed to discover 205 genomic loci where an allele associated with increase adiposity was associated with a lower cardiometabolic disease risk to an individual.

Polygenic scores for body mass index and obesity constructed using data from 5 million people with different ancestries were associated with distinct weight gain trajectories from early childhood to adulthood.

This study uses whole-brain connectome analysis via functional MRI to investigate memory retrieval in individuals with post-traumatic stress disorder and its dissociative subtype, revealing distinct connectivity patterns and disruptions in subcortical–cortical integration during traumatic versus neutral memory processing.

Birds have an excellent ability to learn to discriminate harmless insects from those that they mimic on the basis of subtle differences in appearance.

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.

Malaria control and elimination require environmentally safe strategies. Here, the authors propose L-DOPA, a naturally occurring tyrosine derivative, as a mosquito dietary intervention that can shorten lifespan and reduce malaria parasite burden of female Anopheles gambiae mosquitoes.

Cellular niches are highly heterogenous in triple negative breast cancer. Here, the authors utilise imaging mass cytometry and spatial transcriptomics to characterise the microenvironment in Black American and White American patients.

Progression of chronic kidney disease may lead to kidney failure and cardiovascular, metabolic and bone disease complications. Here, the authors conduct a large-scale proteomic study in patients with chronic kidney disease, identify numerous proteins that predict kidney failure, some of which are likely causal mediators and hence potential therapeutic targets.

The authors found, after analyzing 10,960 individuals from 9 multiancestry biobanks across 6 countries, that genetic factors previously associated with BMI have limited impact on GLP-1 receptor agonist-induced weight loss.

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.

Excised signal circles are circular DNA by-products of V(D)J recombination that form a complex with the V(D)J recombinase, and when increased in abundance, result in increased mutagenesis, causing adverse outcomes in cancer.

In this phase 1 trial, treatment of patients with solid tumors using the focal adhesion kinase (FAK) inhibitor defactinib the RAF–MEK clamp avutometinib was safe and showed encouraging clinical responses, especially in patients with low-grade serous ovarian cancer.

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).

Alzheimer’s disease has been associated with increased structural brain aging. Here the authors describe a model that predicts brain aging from resting state functional connectivity data, and demonstrate this is accelerated in individuals with pre-clinical familial Alzheimer’s disease.

The identification of two cryptic species of the fungal pathogen that causes white-nose disease in bats highlights the need to integrate studies of genetic variability in pathogens into disease surveillance, management and prevention strategies.

By forming a network of experienced peers, says Ruth Gotian, you can gain crucial career guidance and inspiration.

Genome-wide association analysis of gout and urate identifies 148 new loci, implicating biological pathways and prioritizing candidate genes involved in inflammatory processes.

Haematopoietic stem cell numbers are restricted at both systemic and local levels.

Tumour evolution and heterogeneity in high grade serous ovarian cancer (HGSOC) remains poorly characterised. Here, the authors investigate the genomic landscape of HGSOC and reveal two distinct evolutionary trajectories associated with clinical outcomes.

A new study from the eMERGE consortium provides insights on the development of a pipeline for the generation and reporting of polygenic risk scores for ten diseases to diverse populations in a clinical setting.

Using data from a single time point, passenger-approximated clonal expansion rate (PACER) estimates the fitness of common driver mutations that lead to clonal haematopoiesis and identifies TCL1A activation as a mediator of clonal expansion.

Non-pharmaceutical interventions for COVID-19 control impacted transmission of other pathogens including respiratory syncytial virus (RSV). Here, the authors perform phylodynamic analyses of RSV genomes from New Zealand to explore dynamics before, during, and after the COVID-19 pandemic.

The PSA (KLK3) genetic variant rs17632542 is associated with reduced prostate cancer risk and lower serum PSA levels, although the underlying reasons are unclear. Here, the authors show that this PSA variant reduced proteolytic activity and leads to smaller tumours, but also increases invasion and bone metastasis, indicating its dual risk association depending on tumour context; the variant is associated with both lower risk and poor clinical outcomes.

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.

People’s early experiences and dispositions influence their ability to show and feel empathy. Here, using a sample of children exposed to war-related trauma, the authors examine how parenting, temperament, anxiety, and adversity affect the maturation of neural responses associated with empathy.

Substitution of food produce from declining wild fisheries with farmed species may exacerbate prevalent micronutrient deficiencies in regions such as the urban Peruvian Amazon, as well as negatively impact agricultural land use and greenhouse gas emissions.

Wireless bioresorbable stimulators are promising therapeutic implants that naturally dissolve after use. Here, the authors developed a device that operates for months and enables simultaneous multi-site stimulation, preventing early muscle atrophy and accelerating reinnervation in nerve injury models.

Mucociliary clearance is crucial for airway defense but its structure-function relationships in humans are not fully understood. Here, the authors show how airway epithelial structure impacts clearance by mapping cilia distribution, comparing human and rat airways, and developing quantitative models to assess function.

A large genome-wide association study of more than 5 million individuals reveals that 12,111 single-nucleotide polymorphisms account for nearly all the heritability of height attributable to common genetic variants.

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

Ruth Loos and colleagues report results of a large genome-wide association study for body mass index. They identify 18 new loci associated with this trait, some of which map near key hypothalamic regulators of energy balance.