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Nature Biotechnology's readers select some of biotech's most remarkable and influential personalities from the past 10 years.

The genome sequence of segmental allotetraploid peanut suggests that diversity generated by genetic deletions and homeologous recombination helped to favor the domestication of Arachis hypogaea over its diploid relatives.

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.

A genome-wide association meta-analysis study of blood lipid levels in roughly 1.6 million individuals demonstrates the gain of power attained when diverse ancestries are included to improve fine-mapping and polygenic score generation, with gains in locus discovery related to sample size.

Cell type labelling in single-cell datasets remains a major bottleneck. Here, the authors present AnnDictionary, an open-source toolkit that enables atlas-scale analysis and provides the first benchmark of LLMs for de novo cell type annotation from marker genes, showing high accuracy at low cost.

The multistage carcinogenesis theory is largely established and supported, but it can be contradicted by features such as abundant cancer-like genetic or phenotypic changes in normal tissues and the rates of cancer in contralateral organs and patients’ relatives. Here, the authors extend the Peto-Mack postulate to reconcile such incongruences, distinguishing the last multistage hit as the critically rate-limiting event in carcinogenesis.

Divergent trends in biogeochemical constituents of the six largest rivers in the Arctic from 2003 to 2019 support multi-faceted changes on the Arctic landscape under global environmental change.

Meltwaters from the southwestern margin of the Greenland Ice Sheet contain exceptionally high concentrations of mercury, exporting up to more than 200 kmol of dissolved mercury every year, suggest mercury measurements from three glacial catchments.

Toxoplasma gondii can persist in neurons in the central nervous system, presumably because neurons have limited cell-intrinsic immune responses. However, here, Chandrasekaran et al. show that IFN-gamma stimulated primary murine neurons can clear T. gondii and that IFN-gamma stimulated murine and human neurons show decreased infection rates.

A sequencing chemistry that separates nucleotide identification from nucleotide incorporation achieves high accuracy.

Circulating tumour DNA profiling in early-stage non-small-cell lung cancer can be used to track single-nucleotide variants in plasma to predict lung cancer relapse and identify tumour subclones involved in the metastatic process.

The age of the Grand Canyon is fervently debated. Thermochronological reconstructions of canyon incision show that although parts of the canyon were carved more than 50 million years ago, two key segments formed less than 6 million years ago, implying that the canyon is a young feature.

UCHL5 is a deubiquitinating enzyme that cleaves Lys-48-linked polyubiquitin chains. Here, the authors discover through in-vivo CRISPR-Cas9 screens that Uchl5 is involved in immune evasion and modulation of extracellular matrix deposition in head and neck squamous cell carcinoma.

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.

Paul Pharoah, Joellen Schildkraut, Thomas Sellers and colleagues report a meta-analysis of genome-wide association studies for epithelial ovarian cancer and genotyping using the iCOGS array in 18,174 cases and 26,134 controls from 43 studies from the Ovarian Cancer Association Consortium. They identify three new ovarian cancer susceptibility loci, including one specific to the serous subtype, and their integrated molecular analysis of genes and regulatory regions at these loci suggests disease mechanisms.

Researchers can make use of a variety of computational tools to prioritize genetic variants and predict their pathogenicity. Here, the authors evaluate the performance of six of these tools in three typical biological tasks and find generally low concordance of predictions and experimental confirmation.

Healthspan and healthy aging are areas of research with potential socioeconomic impact. Here, the authors present the Medical Genome Reference Bank (MGRB) which consist of over 4,000 individuals aged 70 years and older without a history of the major age-related diseases and report on results from whole-genome sequencing and association analyses.

SAVANA is a tool to detect somatic structural variants and copy number aberrations using long-read sequencing data, offering high sensitivity, specificity and compatibility with or without germline controls.

The authors collate a meta-collection of ex situ living plant diversity held in 50 botanical collections worldwide, spanning a century of data and currently containing ~500,000 accessions. Their analyses examine the capacities and constraints within living plant collections, reveal the impact of the Convention on Biological Diversity and its consequences for material exchange and conservation, and call for the re-evaluation of strategic priorities.

With an improved framework for model development and evaluation, a large language model is shown to provide answers to medical questions that are comparable or preferred with respect to those provided by human physicians.

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.

Although plant functional trait combinations reflect ecological trade-offs at the species level, little is known about how this translates to whole communities. Here, the authors show that global trait composition is captured by two main dimensions that are only weakly related to macro-environmental drivers.

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.

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.

Mosaic chromosomal alterations (mCAs) in peripheral blood leukocytes are associated with an increased risk of malignancy. Here, the authors use genome-wide genotyping array data to investigate the prevalence of mCAs in sub-Saharan African children with versus those without Burkitt lymphoma.

Analyses of expression profiles from whole blood of 31,684 individuals identify cis-expression quantitative trait loci (eQTL) effects for 88% of genes and trans-eQTL effects for 37% of trait-associated variants.

Forscher et al. probe whether grant reviewers discriminate on the basis of principal investigator race or gender. In an experiment involving 412 active scientists, the authors find no evidence of pragmatically important bias.

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.

Protein interactions are essential for neural signaling and often perturbed in brain conditions. Here, the authors developed a CRISPR-based chemical-genetic approach to identify endogenous proximity proteomes that inform mechanism and phenotypic rescue strategies in mouse models of autism.

Mutations in amyloid precursor protein (APP) and presenilin 1 (PSEN1) cause autosomal dominant AD (ADAD). Here, the authors perform single-nucleus RNA-sequencing of ADAD and other disease risk modifying variant carriers and report altered expression states of specific brain cell types.

Most confirmed susceptibility variants for epithelial ovarian cancer lie in non-protein-coding sequences. Here Permuth-Wey and colleagues investigate variants in 3′ untranslated regions (UTRs) and uncover a new susceptibility locus.

Here, the authors present a TWAS framework OTTERS that adapts multiple polygenic risk score methods to estimate eQTL weights from summary-level eQTL data. Both simulation and real studies show OTTERS is powerful across a wide range of genetic architectures.

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.

An α-helical region conserved among FOXA pioneer factors interacts with core histones and promotes chromatin opening in vitro. This region also promotes chromatin opening in early mouse embryos and is required for normal development.

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.

In this study the authors identify a possible link between the gene FAM222A and brain atrophy. The protein it encodes is found to accumulate in plaques seen in Alzheimer’s disease, and functional analysis suggests it interacts with amyloid-beta.

Systemic dissection of sexually dimorphic phenotypes in mice is lacking. Here, Karp and the International Mouse Phenotype Consortium show that approximately 10% of qualitative traits and 56% of quantitative traits in mice as measured in laboratory setting are sexually dimorphic.

The NUP98–HOXA9 oncogenic fusion protein found in leukaemia undergoes phase separation in the nucleus, which helps to promote activation of leukaemic genes and to establish aberrant chromatin looping.

DICER1 is required for the maturation of miRNAs which regulate expression of thousands of genes. Here the authors show significantly reduced levels of DICER1in individuals having post-traumatic stress disorder and comorbid depression suggestive of a role in the molecular mechanism of the condition.

Tsinghua University's Chen Jining is slated to become environmental-protection minister as China steps up efforts to clean up its air, water and soil.

The study of germline mutations has been greatly enhanced by massive parallel sequencing technologies. Here the authors use deep sequencing data from nearly 700 parent-child trios to show maternal age has a small but significant correlation with the number of de novomutations in the offspring.

Activation of the non-canonical NF-κB signalling pathway by AZD5582 results in the induction of HIV and SIV RNA expression in the blood and tissues of antiretroviral-therapy-treated humanized mice and rhesus macaques.

The fusion gene ZMYND11-MBTD1 (ZM) is present in a subgroup of patients with acute myeloid leukaemia (AML). Here, the authors show that ZM expression induces AML in a murine model though activating the NuA4/TIP60 histone acetyltransferase complex.

Recent experience can only provide limited information to guide decisions in a volatile environment. Here, the authors report that the choices made by a monkey in a dynamic foraging task can be better explained by a model that combines learning on both fast and slow timescales.

Targeted protein degradation has so far been rarely applied as an antiviral strategy. Here, the authors report that macrocycle-based PROTACs targeting host protein cyclophilin A, exploited during viral infection, show potent and isoform-selective degradation resulting in antiviral activity against HIV-1 and HCV.

Structural variants (SVs) contribute to the genetic architecture of many brain-related disorders. Here, the authors integrate SV calls from genome sequencing (n = 755) with RNA-seq data (n = 629) from post-mortem dorsal lateral prefrontal cortex to annotate the gene regulatory effects of SVs in the human brain and their potential to contribute to disease.