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MaizeCODE maps active regulatory regions tied to maize domestication traits in a diverse panel of tissues and inbreds. It reveals bi-directional enhancer RNAs and the molecular conflicts between activity and silencing of non-coding regions.

Generation and analysis of high-quality, genome assemblies from Middle Eastern trios demonstrate the utility of ancestry-matched data and assembly-based variation analysis.

Cytoplasmic, amyloid-like oligomeric assemblies that contain TDP-43 are increased in damaged tissues with elevated regeneration, thereby enhancing the possibility of amyloid fibre formation and/or aggregation of TDP-43 in disease.

Analysis of more than 95% of each diploid human genome of a four-generation, twenty-eight-member family using five complementary short-read and long-read sequencing technologies provides a truth set to understand the most fundamental processes underlying human genetic variation.

The authors show that the deletion of ultraconserved TAD boundaries affects gene expression and phenotype, highlighting TAD evolution’s function. Human-specific TAD boundaries reveal a role in brain development and disease.

The modelling of human-like behaviours is one of the challenges in the field of Artificial Intelligence. Inspired by experimental studies of cultural evolution, the authors propose a reinforcement learning approach to generate agents capable of real-time  third-person imitation.

A study reports whole-genome sequences for 490,640 participants from the UK Biobank and combines these data with phenotypic data to provide new insights into the relationship between human variation and sequence variation.

Here, the authors show that SARS-CoV-2 infection causes gut microbiome dysbiosis and gut epithelial cell alterations in a mouse model, and correlate dysbiosis observed in COVID-19 patients with blood stream infections, matching reads of bacterial sequences from stool samples to organisms found in the blood.

cAMPFIREs are genetically encoded cAMP sensors that are suitable for in vivo imaging of cAMP signaling, as demonstrated in Drosophila larvae and behaving mice.

An initial draft of the human pangenome is presented and made publicly available by the Human Pangenome Reference Consortium; the draft contains 94 de novo haplotype assemblies from 47 ancestrally diverse individuals.

Locityper is a general-purpose genotyper that can efficiently genotype and analyze a diverse set of genes, such as hyperpolymorphic HLA genes, using both short-read and long-read whole-genome sequencing data.

Reference assemblies of great ape sex chromosomes show that Y chromosomes are more variable in size and sequence than X chromosomes and provide a resource for studies on human evolution and conservation genetics of non-human apes.

MRP4 is an ATP-binding cassette transporter that transports prostanoids, a group of signaling molecules. The authors use cryo-EM to visualize the transport cycle and characterize its substrate selectivity.

Results for the final phase of the 1000 Genomes Project are presented including whole-genome sequencing, targeted exome sequencing, and genotyping on high-density SNP arrays for 2,504 individuals across 26 populations, providing a global reference data set to support biomedical genetics.

Methods to produce haplotype-resolved genome assemblies often rely on access to family trios. The authors present FALCON-Phase, a tool that combines ultra-long range Hi-C chromatin interaction data with a long read de novo assembly to extend haplotype phasing to the contig or scaffold level.

A high-quality bonobo genome assembly provides insights into incomplete lineage sorting in hominids and its relevance to gene evolution and the genetic relationship among living hominids.

A comparison of two complete sets of human centromeres reveals that the centromeres show at least a 4.1-fold increase in single-nucleotide variation compared with their unique flanks, and up to 3-fold variation in size, resulting from an accelerated mutation rate.

Neurodevelopmental disorders (NDDs) are a heterogeneous group of diseases for which the genetic basis is still unknown in more than half of the cases. Here, the authors report a NDD associated with disruptive variants in the TANC2 gene and show that rols, the TANC2 homolog in flies, is required for synapse growth and function.

Solid organ transplant recipients are at increased risk of infectious disease and have unique molecular pathophysiology. Here the authors use host-microbe profiling to assess SARS-CoV-2 infection and immunity in solid organ transplant recipients, showing enhanced viral abundance, impaired clearance, and increased expression of innate immunity genes.

The Somatic Mosaicism across Human Tissues Network aims to create a reference catalogue of somatic mosaicism across different tissues and cells within individuals.

Jayavelu, Samaha et al., apply machine learning models on hospital admission data, including antibody titers and viral load, to identify patients at high risk for Long COVID. Low antibody levels, high viral loads, chronic diseases, and female sex are key predictors, supporting early, targeted interventions.

The role of IgG glycosylation in the immune response has been studied, but less is known about IgM glycosylation. Here the authors characterize glycosylation of SARS-CoV-2 spike specific IgM and show that it correlates with COVID-19 severity and affects complement deposition.

Evan Eichler and colleagues report an estimate of the mutation rate in humans that is based on the whole-genome sequences of five parent-offspring trios from a Hutterite population and genotyping data from an extended pedigree. They use a new approach for estimating the mutation rate over multiple generations that takes into account the extensive autozygosity in this founder population.

An example of hybrid incompatibility between maize and teosinte reveals a selfish toxin–antidote system mediated by small RNAs that may have contributed to the origin of maize.

The BRAIN Initiative Cell Census Network has constructed a multimodal cell census and atlas of the mammalian primary motor cortex in a landmark effort towards understanding brain cell-type diversity, neural circuit organization and brain function.

A study comparing the pattern of single-nucleotide variation between unique and duplicated regions of the human genome shows that mutation rate and interlocus gene conversion are elevated in duplicated regions.

Integration of long and ultra-long reads results in improved phased, diploid assemblies.

Comparative genomic analysis of human and primate relatives can reveal important biological and evolutionary insights. Here, the authors present a long-read assembly of the Chinese rhesus macaque genome and identify ape-specific structural variants.

In neurons the membrane-associated periodic skeleton (MPS) consists of actin, spectrin, and associated molecules. Here the authors use proteomic analysis and super-resolution imaging to provide insight into the molecular composition and organization of the MPS, and its functions in axon-diameter regulation and neurite-neurite interactions.

Chimeric antigen receptor (CAR) T cells engineered to overexpress the canonical AP-1 transcription factor c-Jun are resistant to T cell exhaustion, and provide enhanced therapeutic benefit in mouse tumour models.

We present the complete 62,460,029-base-pair sequence of a human Y chromosome from the HG002 genome (T2T-Y) that corrects multiple errors in GRCh38-Y and adds over 30 million base pairs of sequence to the reference.

Zong et al. reveal that genetic and pharmacologic inhibition of TRPM7 channel function prevents the activation of Ca²⁺–CaM–calcineurin–KLF4 signaling, the phenotypic switch of vascular smooth muscle cells and the formation of abdominal aortic aneurysms.

The Structural Variation Analysis Group of The 1000 Genomes Project reports an integrated structural variation map based on discovery and genotyping of eight major structural variation classes in 2,504 unrelated individuals from across 26 populations; structural variation is compared within and between populations and its functional impact is quantified.

Analysis of whole-genome sequence data from 3,474 families finds an excess of private, likely gene-disrupting variants in individuals with autism. These variants are under purifying selection and suggest candidate genes not previously associated with autism.

An approach involving combinatorial peptide–MHC tetramer staining and mass cytometry allows simultaneous screening of over 100 T-cell specificities in a single human blood sample.

Duplications of gene segments can allow novel physiological adaptations to evolve. A detailed analysis of the TCAF gene family in primates and archaic humans suggest rapid duplication and diversification in this gene family is associated with cold or dietary adaptations.

Population recordings reveal that neurons in the mouse superior colliculus are grouped according to their preferred orientations or movement axes for visual line stimuli, similar to the columnar arrangement in visual cortex of higher mammals; this functional architecture suggests that the superior colliculus samples the visual world unevenly for stimulus orientations.

The complete assembly of human chromosome 8 resolves previous gaps and reveals hidden complex forms of genetic variation, enabling functional and evolutionary characterization of primate centromeres.

Sequencing of the bonobo genome shows that more than three per cent of the human genome is more closely related to either the bonobo genome or the chimpanzee genome than those genomes are to each other.

The Splitread algorithm uses a split-read strategy to detect structural variants and small insertions and deletions (indels) in whole-exome and whole-genome sequence datasets at high sensitivity. It maps the breakpoints at single-base-pair resolution, even in low-complexity regions, and can detect novel processed pseudogenes.

Combinations of fluorescently labeled peptide–major histocompatability (pMHC) tetramers are used to simultaneously detect T cells with multiple antigen specificities from human blood samples. Also in this issue, Hadrup et al. present a very similar combinatorial encoding approach.

A comparative segmental duplication map of four primate genomes that allows the evolutionary history of all human segmental duplications to be reconstructed is presented. It reveals a fourfold acceleration of segmental duplication accumulation during the speciation of human, chimpanzee and gorilla at a time when other mutational processes were slowing, and also provides a detailed evolutionary history of all human segmental duplications as a resource to the human genetics community.

Sequencing a human genome using next-generation methods does not distinguish between the two copies of each chromosome. Kitzman et al. determine a haplotype-resolved genome sequence by efficiently constructing and sequencing long-insert clones that cover the diploid genome with a low likelihood of overlap.

Noninvasively monitoring immune function by positron emission tomography could affect the diagnosis and treatment evaluation of immunological disorders. Progress, however, has been hampered by the lack of probes with distinct biodistribution patterns. Radu et al. exploit the fact that many immune cells utilize a salvage pathway for nucleotide generation during DNA synthesis to develop [¹⁸F]FAC (1-(2′-deoxy-2′[¹⁸F]fluoroarabinofuranosyl) cytosine), a new probe with increased accumulation in proliferating T cells. Studies in mice show it has advantages over commonly used probes and may be clinically useful.

Thomas Sander and colleagues identify 15q13.3 microdeletions in 1% of individuals with idiopathic generalized epilepsy (IGE). The majority of these individuals do not show intellectual disability, schizophrenia or other neuropsychiatric phenotypes, thus extending the phenotypic spectrum associated with 15q13.3 microdeletions.