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cfDNA fragmentomics is a potential clinically applicable method for identifying cancer. Here, the authors assess fragmentomics analysis methods and their application to commercial targeted sequencing panels.

The cortex fuels essential physiological processes with glucose-derived carbon, while gliomas fuel their aggressiveness by rerouting glucose carbon pathways and scavenging alternative carbon sources such as environmental amino acids, providing a potential therapeutic target.

In 1994, George Rose and Trevor Creamer proposed the ‘Paracelsus challenge’, offering $1,000 to the first person who could show a pair of proteins that have different topologies, yet no less than 50% sequence identity. The challenge has now been met by a group who have created the aptly named Janus protein. Janus shares 50% sequence identity with the B1 domain of the Streptococcal protein G - which is mainly beta-sheet - yet it folds into a helical structure that resembles the four-helix-bundle protein Rop.

Inorganic–organic hybrid dye-sensitized solar cells featuring a perovskite compound as a light harvester and a polymer as a hole transporter provide an open-circuit voltage of almost 1 V and a power conversion efficiency of 12% under standard illumination conditions.

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.

Stereotactic needle biopsies are currently performed for diagnosis only in glioblastoma; this study highlights the depth of information available through multi-omics analysis.

MultiSTAAR provides a general and flexible statistical framework for functionally informed multi-trait rare variant analysis of biobank-scale sequencing studies by jointly analyzing multiple traits and incorporating annotation information.

Although the triiodide/iodide redox couple works efficiently in dye-sensitized solar cells it restricts functionality by absorbing visible light. Now, a disulfide/thiolate redox couple that has negligible absorption in the visible spectral range is presented, which in conjunction with a sensitized heterojunction, displays an efficiency of 6.4% under standard illumination test conditions.

Analysis of whole-genome sequences of 25,465 individuals of European ancestry shows that rare variants contribute substantially to the heritability of height and body mass index.

Here, the authors leverage whole-genome sequencing from >88,000 diverse individuals to uncover 18 BMI-related genetic signals, including novel variants in participants of African genetic ancestry, highlighting the value of diversity in genetic discovery.

Genome-wide association analyses comprising 14,256 cases and 1,199,156 controls and incorporating correlated cardiac magnetic resonance imaging traits provide insights into the molecular etiology of dilated cardiomyopathy.

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.

AI decision support system non-homogenously influences clinical decisions in dynamic treatment regimen, as it depends on several factors including prior knowledge, preference, disease type, treatment modality, and AI’s learned behavior and inherent biases.

Neurostimulation has been proposed as a potential approach for treatment-resistant PTSD. Here in a pilot study the authors show that amygdala theta activity is heightened during aversive and symptomatic experiences in patients with treatment-resistant post-traumatic stress disorder, and reduced following significant clinical improvement associated with closed-loop stimulation.

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

Whole genome sequences enable discovery of rare variants which may help to explain the heritability of common diseases. Here the authors find that ultra-rare variants explain ~50% of coronary artery disease (CAD) heritability and highlight several functional processes including cell type-specific regulatory mechanisms as key drivers of CAD genetic risk.

The origin of hysteresis remains an open question in lead-halide perovskite solar cells. Here, Meloni et al. investigate the causes of hysteresis using an experimental and computational approach, finding that the observed hysteresis is due to halide ion-vacancy movement in the perovskite.

After two decades of research, the efficiency of dye-sensitized solar cells seems to have reached a plateau. Now, changing both electrolyte and dye opens up new opportunities that offer the hope that the efficiency ceiling can be broken.

The goals, resources and design of the NHLBI Trans-Omics for Precision Medicine (TOPMed) programme are described, and analyses of rare variants detected in the first 53,831 samples provide insights into mutational processes and recent human evolutionary history.

Although the common genetic variants contributing to blood lipid levels have been studied, the contribution of rare variants is less understood. Here, the authors perform a rare coding and noncoding variant association study of blood lipid levels using whole genome sequencing data.

STAARpipeline is a comprehensive framework for flexible and scalable rare-variant association analysis using whole-genome sequencing data and annotation information.

The influence of X chromosome genetic variation on blood lipids and coronary heart disease (CHD) is not well understood. Here, the authors analyse X chromosome sequencing data across 65,322 multi-ancestry individuals, identifying associations of the Xq23 locus with lipid changes and reduced risk of CHD and diabetes mellitus.

A study shows that clonal haematopoiesis of indeterminate potential is associated with an increased risk of chronic liver disease specifically through the promotion of liver inflammation and injury.

Most studies of the genetics of the metabolome have been done in individuals of European descent. Here, the authors integrate genomics and metabolomics in Black individuals, highlighting the value of whole genome sequencing in diverse populations and linking circulating metabolites to human disease.

Alterations in the tumour suppressor genes STK11 and/or KEAP1 can identify patients with advanced non-small-cell lung cancer who are likely to benefit from combinations of PD-(L)1 and CTLA4 immune checkpoint inhibitors added to chemotherapy.

Genome-wide association meta-analyses identify 26 risk loci for epilepsy, including 19 loci specific to genetic generalized epilepsy. Prioritized candidate genes implicate synaptic processes and overlap with targets of antiseizure medications.

Pooling participant-level genetic data into a single analysis can result in variance stratification, reducing statistical performance. Here, the authors develop variant-specific inflation factors to assess variance stratification and apply this to pooled individual-level data from whole genome sequencing.

Analysis of 97,691 high-coverage human blood DNA-derived whole-genome sequences enabled simultaneous identification of germline and somatic mutations that predispose individuals to clonal expansion of haematopoietic stem cells, indicating that both inherited and acquired mutations are linked to age-related cancers and coronary heart disease.

Platelet aggregation is associated with myocardial infarction and stroke. Here, the authors have conducted a whole genome sequencing association study on platelet aggregation, discovering a locus in RGS18, where enhancer assays suggest an effect on activity of haematopoeitic lineage transcription factors.

IL-35 is an immunomodulatory cytokine secreted by regulatory T cells. Vignali and colleagues demonstrate that IL-35 also mediates the induction of a unique regulatory population that may underpin infectious tolerance.

In this largest whole-exome sequencing study of epilepsies to date, the Epi25 Collaborative identified extremely rare variants that confer risk for diverse epilepsy subtypes, highlighting roles in synaptic transmission and neuronal excitability.

In this study, Massachusetts Consortium for Pathogen Readiness (MassCPR) investigators assess the relationship between SARS-CoV-2 viral load and COVID-19 disease severity and report that the levels of detectable viral RNA, especially in plasma, correlates with severity of respiratory disease, inflammatory markers and predicted risk of death.

This Article reports the emergence of SARS-CoV-2 escape mutations during bamlanivimab therapy in the setting of a phase II clinical trial.

Michael Cho and colleagues report a genome-wide association study for chronic obstructive pulmonary disease, identifying a susceptibility locus at chromosome 4q22.1 in FAM13A.

Miller et al. use fast thermal preservation and mass spectrometry imaging to reveal rapid neuron-layer metabolic responses to stimulation within a brain slice. Stimulation increases glucose use and converts spent ATP into metabolic fuel, via inosine.

Here, Li et al. perform a genome-wide CRISPR screen to identify host dependency factors for influenza A virus infection and show that the host mRNA cap methyltransferase CMTR1 is important for viral cap snatching and that it affects expression of antiviral genes.