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The authors summarize the data produced by phase III of the Encyclopedia of DNA Elements (ENCODE) project, a resource for better understanding of the human and mouse genomes.

A single-cell epigenomic atlas of human immune cells highlights cell-type-specific features associated with genetic or environmental exposures.

A long-standing controversy surrounds low-angle nature of observed detachment faults within metamorphic core complexes. Here, the authors show that post-orogenic collapse of mountain belts can create a low-angle detachment, resolving the controversy.

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

The clinical course of chronic lymphocytic leukaemia (CLL) is variable and difficult to predict. Here, the authors conduct a genome wide association study meta-analysis for time to first treatment in CLL patients and report two loci associating with progressive disease.

A genome-wide association study including over 76,000 individuals with schizophrenia and over 243,000 control individuals identifies common variant associations at 287 genomic loci, and further fine-mapping analyses highlight the importance of genes involved in synaptic processes.

The use of PET for detection of Aβ in the brain in AD has limitations; studies also indicate that retinal changes, including Aβ deposition, occur in AD. Here the authors demonstrate the potential to use in vivo retinal hyperspectral imaging as a surrogate for brain accumulation of Aβ.

A global map of human subcellular architecture yields protein complex structures, reveals protein functions, identifies assemblies with multiple localizations or cell-type specificity and decodes paediatric cancer genomes.

The heterogenous nature of rheumatoid arthritis renders the prediction of responsiveness to biological treatments difficult. Here the authors analyze bulk RNA-seq data from the STRAP trial (n = 208) to build a machine-learning model for predicting responses to etanercept, tocilizumab and rituximab with AUCs around 0.75 to potentially assist in therapy planning.

Dimethyl fumarate (DMF) is an anti-inflammatory drug proposed as a treatment for COVID19. Here the results are reported from a randomised trial testing DMF treatment in 713 patients hospitalised with COVID-19. DMF was not associated with any improvement in day 5 outcomes.

A combination of five assays is used to produce a catalogue of RNA elements to which RNA-binding proteins bind in human cells.

Prospective testing of a clinical fiberscope with a lightproof enclosure for Cerenkov luminescence imaging using five different radiotracers showed satisfactory agreement with standard-of-care nuclear imaging for tumour location.

Peptide secondary metabolites have a diverse range of functions. Here the authors present a method to design and screen a large library of modified peptides in E. coli against a target of interest.

Abnormal functions of RNA-binding proteins TAF15, FUS and TDP43 are associated with amyotrophic lateral sclerosis. Here, Kapeli et al. characterize the RNA targets of TAF15 and identify points of convergence and divergence between the targets of TAF15, FUS and TDP43 in several neuronal systems.

Biomarker analysis of the phase 4 R4RA trial identifies pretreatment synovial biopsy features selectively associated with response to rituximab or tocilizumab, and leads to the development of models that might predict treatment benefit in patients with rheumatoid arthritis

Targeting genotype-independent abnormalities may overcome therapy resistance in glioblastoma despite intratumoral genomic heterogeneity. Here, the authors show that glioblastoma radiation resistance is promoted by purine metabolism and can be overcome by inhibitors of purine synthesis.

Intraspecies response to climate change is expected to align with genetic affinity. Using the American pika as a case study suggests that divisions of species distributions best explain intraspecific heterogeneity in climate relationships.

GATA2 regulatory mutations are associated with hereditary congenital facial paresis in humans. A genetically engineered mouse model recapitulates the human phenotype, showing altered neuron-specific Gata2 expression and a bias in formation of inner-ear efferent neurons over facial branchial motor neurons.

SF3B1 mutations confer sensitivity to poly (ADP-ribose) polymerase inhibitors (PARPi). Mechanistically, this is independent of homologous recombination repair and instead relies on a defective replication stress response due to a reduction of the cyclin-dependent kinase 2 interacting protein (CINP). PARPi treatment of SF3B1 mutant (SF3B1^MUT) tumors leads to replication stress induced by increased fork origin firing and culminates in cell cycle stalling.

Integration of GWAS and single-cell transcriptomic data from the entire nervous system systematically identifies cell types underlying brain complex traits and provides insights into the etiology of Parkinson’s disease.

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.

Differential binding of RNA-binding proteins mediated by genetic variants (GVs) can influence posttranscriptional regulation. Here, the authors develop BEAPR, a computational approach to identify allele-specific binding events in eCLIP-Seq data.

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.

Resource constraints and environmental impacts associated with current phosphorus fertilizer manufacture and use highlight considerable risks within global food production systems. Research portfolios targeted at existing soil phosphorus reserves might offer a solution.

A new brain mapping approach tailored to individual people reveals that volume changes in psychiatric illness occur in highly variable locations across individuals, but that these differences often aggregate within common brain systems.

The authors defined a roadmap for investigating the genetic covariance between structural or functional brain phenotypes and risk for psychiatric disorders. Their proof-of-concept study using the largest available common variant data sets for schizophrenia and volumes of several (mainly subcortical) brain structures did not find evidence of genetic overlap.

Globally diarrheal disease through contaminated water sources is a major cause of child mortality. Here, the authors compile a database of 293,362 children in 35 countries and find that upstream tree cover is linked to a lower probability of diarrheal disease and that increasing tree cover may lower mortality.

Sea-ice leads (open water channels), which increase with an ongoing shift from perennial to seasonal sea ice, are shown to initiate convection in the Arctic boundary layer, thus supplying ozone and gaseous mercury to the surface and possibly leading to additional pollution effects.

Whole-genome sequencing of chronic lymphocytic leukemia from 485 patients identifies putative coding and noncoding drivers of disease. Genomically defined subgroups show distinct clinical and biological characteristics.

Genome-wide analyses identify eight independent loci associated with anorexia nervosa. Genetic correlations implicate both psychiatric and metabolic components in the etiology of this disorder, even after adjusting for the effects of common variants associated with body mass index.