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Humanity’s Last Exam, a multi-modal benchmark at the frontier of human knowledge, is designed to be an expert-level closed-ended academic benchmark with broad subject coverage.

The authors present DNA-Diffusion, a generative AI framework that designs synthetic regulatory elements with tunable cell-type specificity. Experimental validation demonstrates their ability to reactivate AXIN2 expression, a leukemia-protective gene, in its native genomic context.

A consensus cell type atlas for the fly brain provides both an intellectual framework and open-source toolchains for brain-scale comparative connectomics.

REM-sleep behavior disorder often precedes Parkinson’s disease or dementia. Here, the authors perform a genome-wide association study for REM-sleep behavior disorder, and discover how it potentially affects gene expression in the brain.

Meta-analysis of genome-wide association studies on Alzheimer’s disease and related dementias identifies new loci and enables generation of a new genetic risk score associated with the risk of future Alzheimer’s disease and dementia.

A genome-wide association study performed in 1,126,563 individuals identifies seven new loci associated with Alzheimer’s disease and implicates microglia and immune cells in late-onset disease.

This study uses epi-retro-seq to link single-cell epigenomes and cell types to long-distance projections for neurons dissected from different regions projecting to different targets across the whole mouse brain.

Visual signals that help individuals recognize their own species are predicted to be distinct from those of closely related sympatric species, but evidence for this pattern is scarce. Here, Allen et al.show guenon faces are distinctive, specifically from those of other guenon species they encounter.

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.

Aardvark Weather, an end-to-end machine learning model, replaces the entire numerical weather prediction pipeline with a machine learning model, by producing accurate global and local forecasts without relying on numerical solvers, revolutionizing weather prediction with improved speed, accuracy and customization capabilities.

FlyWire presents a neuronal wiring diagram of the whole fly brain with annotations for cell types, classes, nerves, hemilineages and predicted neurotransmitters, with data products and an open ecosystem to facilitate exploration and browsing.

An ambitious project to map the mouse brain at the Allen Institute for Brain Science is a huge undertaking that may unify neuroscience, argue Christof Koch and R. Clay Reid.

Surface two-photon imaging of the brain cannot access somatic calcium signals of neurons from deep layers of the macaque cortex. Here, the authors present an implant and imaging system for chronic motion-stabilized two-photon imaging of dendritic calcium signals to drive an optical brain-computer interface in macaques.

Sera from vaccinated individuals and some monoclonal antibodies show a modest reduction in neutralizing activity against the B.1.1.7 variant of SARS-CoV-2; but the E484K substitution leads to a considerable loss of neutralizing activity.

Large genome-wide meta-analysis of clinically diagnosed late-onset Alzheimer’s disease (LOAD) from 94,437 individuals identifies new LOAD risk loci and implicates Aβ formation, tau protein binding, immune response and lipid metabolism.

Microbial plant-soil feedbacks (PSF) are fundamentally important for plant diversity. The authors present a spatially explicit dynamic model that separates the effects of microbial mutualists and pathogens, thereby presenting a testable mechanistic framework to reconcile previously puzzling observations of the strength and direction of PSF with diversity maintenance.

A study of the evolution of the SARS-CoV-2 virus in England between September 2020 and June 2021 finds that interventions capable of containing previous variants were insufficient to stop the more transmissible Alpha and Delta variants.

Chronic infection with SARS-CoV-2 leads to the emergence of viral variants that show reduced susceptibility to neutralizing antibodies in an immunosuppressed individual treated with convalescent plasma.

COVID-19 can be associated with neurological complications. Here the authors show that markers of brain injury, but not immune markers, are elevated in the blood of patients with COVID-19 both early and months after SARS-CoV-2 infection, particularly in those with brain dysfunction or neurological diagnoses.

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

The genome of the grey short-tailed opossum Monodelphis domestica has been sequenced and analyzed, giving a first peek at a marsupial's genetic code. Of particular interest are the genetics of the immune system, which has been studied as a model for humans, and of the X chromosome for historical reasons.

An international consortium reports the genomic sequence for ten Drosophila species, and compares them to two other previously published Drosophila species. These data are invaluable for drawing evolutionary conclusions across an entire phylogeny of species at once.

Facemap is a data analysis framework for tracking keypoints on mouse faces and relating them to large-scale neural activity. Both of these steps use state-of-the-art convolutional neural networks to achieve high precision and fast processing speeds.

The results of a series of genetic experiments indicate that Foxo1 has a pivotal, Foxp3-independent role controlling regulatory T-cell function.

Assessing the accuracy of evapotranspiration (ET) data is crucial for managing the water used by crops and natural vegetation. This study presents a comprehensive evaluation of the accuracy of a remotely sensed ET model ensemble from the OpenET system using in situ ET measurements collected across the contiguous United States.

Two manifestos call for climate action on different scales — national and global. By Maria Ivanova.

This Perspective discusses how high-energy-density physics could tap the potential of AI-inspired algorithms for extracting relevant information and how data-driven automatic control routines may be used for optimizing high-repetition-rate experiments.

Natasha Bertelsen et al. develop a computational model to categorize patients with autism spectrum disorder (ASD) into distinct subgroups, based on social-communicative or restricted repetitive behaviors. By integrating publicly available neuroimaging and genetic data, they report neural and molecular signatures in two of these subgroups, altogether highlighting subtle differences in neural circuitry and genomic networks that could underlie phenotypic differences among ASD patients.

Tim Lu's synthetic-biology research at Massachusetts Institute of Technology in Cambridge combines biological engineering with electronics and computer science to create bacteria that make structural proteins containing tiny semi-conductors called quantum dots. He explains how genome-editing techniques are furthering his research and their role in treating disease.

A community computational challenge generates algorithms to predict activity of drug combinations.

Preserving spatial information in gene expression analyses is key for interpreting the single-cell tissue context (and even subcellular environments) of RNAs to achieve a more complete understanding of the underlying physiology. This Innovation article describes the emerging technologies of and biological insights from spatially resolved transcriptomics technologies, and how they set the stage for comprehensive investigations using complementary omic approaches.

Here, the authors discuss issues relating to the co-development of targeted cancer therapies and companion diagnostics that were not covered in depth in the draft guidance released by the US Food and Drug Administration in 2011. They propose potential strategies that will be useful to mitigate challenges and to help guide the future co-development of drugs and diagnostics.

CT-SLEB, a powerful and scalable method, improves the performance of multiancestry polygenic prediction by generating polygenic risk scores based on GWAS summary statistics in diverse populations.

A community of researchers report the lessons learned from applying 44 algorithms to predict drug sensitivity in cancer cell lines using genomic, epigenetic and proteomic datasets

Biomarkers predicting response to chemotherapy in patients with muscle-invasive bladder cancer (MIBC) have the potential to better select patients for treatment and to improve outcomes of this aggressive disease. Results from a new study bring us a step closer to individualizing treatment through use of a three-gene signature to predict response to neoadjuvant chemotherapy.

The ideal vascular access for hemodialysis would have a long functional life, facilitate blood flow sufficient to achieve dialysis prescription, and have a low rate of associated complications. This Review assesses the success with which available forms of access fulfill these criteria. The discussion is set in the context of the 2000 K/DOQI dialysis access guidelines and data published in the past 5 years.

Antibiotic resistance seriously threatens our ability to treat infectious diseases. The genes conferring resistance can easily move between organisms, resulting in nearly untreatable diseases. Jo Handelsman and colleagues describe how resistance is spread, the origin of the genes conferring this resistance and the roles they may have in their natural environments.

Two centuries on from the Luddite insurrection, David Edgerton celebrates today's most important opponents to new ideas, inventions and innovations: scientists.

An increasing number of genes have been identified that control the specification and development of projection neuron subtypes in the neocortex. Macklis and colleagues review recent progress in understanding their function and discuss the implications for progenitor plasticity.

Hepatocellular carcinoma (HCC) is the fifth most commonly occurring cancer and the third most common cause of cancer-related deaths, and the incidence of this cancer is increasing. A substantial portion of HCCs are thought to arise from hepatic stem cells. In this Review, Lopa Mishra and colleagues describe TGF-β signalling in liver stem cell niches, and examine the roles of this cytokine including those in tumour progression and suppression. Important translational studies that are needed to develop novel therapies are discussed.