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Precisely tuning the genetic response to environmental stimuli is a key step in engineering synthetic biology systems. Here, the authors profile 8269 IPTG-induced promoters to deconstruct the relationship between sequence architecture and gene expression.

Infections with bacteria of the genus Sarcina are associated with gastric diseases of unclear etiology. Here, Owens et al. show that infection with a distinct Sarcina species is strongly associated with a lethal disease that affects sanctuary chimpanzees in Sierra Leone.

Whole-genome sequencing and phenotype data sharing are introduced in a national health system to streamline diagnosis and to discover coding and non-coding variants that cause rare diseases.

This study uses gene expression predictors for the dorsolateral prefrontal cortex and other brain regions to perform a transcriptomic imputation analysis of schizophrenia, identifying 413 genic associations across 13 brain regions and 36 significantly enriched pathways.

Dysregulation of ribonucleoprotein complex granules, previously implicated in neuromuscular disease, can drive pathogenesis in a genetic form of dilated cardiomyopathy, as shown in gene-edited pigs and patient-derived cardiomyocytes.

Robert de Moya et al. use comparative genomics of avian lice to reconstruct the phylogeny of these parasites. They show that feather lice diversified on the common ancestor of waterfowl and landfowl, and then radiated onto other avian lineages through host-switching.

Phenotypic variation and diseases are influenced by factors such as genetic variants and gene expression. Here, Barbeira et al. develop S-PrediXcan to compute PrediXcan results using summary data, and investigate the effects of gene expression variation on human phenotypes in 44 GTEx tissues and >100 phenotypes.

Primary production and degradative processes impact the carbon to nitrogen ratio of particulate organic matter with depth, according to analysis of seawater samples from the northwest Sargasso Sea.

Common genetic variants associated with plasma lipids have been extensively studied for a better understanding of common diseases. Here, the authors use whole-genome sequencing of 16,324 individuals to analyze rare variant associations and to determine their monogenic and polygenic contribution to lipid traits.

Circulating lipoprotein(a) is an important risk factor for cardiovascular disease and shows variability between different ethnic groups. Here, Zekavat et al. perform whole-genome sequencing in individuals of European and African ancestries and find ancestry-specific genetic determinants for lipoprotein(a) levels.

Individuals with different genotypes may respond differently to environmental variation. Here, Favé et al. find substantial impacts of different environment exposures on the transcriptome and clinical endophenotypes when controlling for genetic ancestry by analyzing data from ∼1000 individuals from a founder population in Quebec.

Limb regeneration requires a blastema with progenitor cells, immune cells, and an overlying wound epidermis, but molecular identities of these populations are unclear. Here, the authors use single-cell RNA-sequencing to identify transcriptionally distinct cell populations in adult axolotl limb blastemas.

Laser microdissection and microarrays are used to assess 900 precise subdivisions of the brains from three healthy men with 60,000 gene expression probes; the resulting atlas allows comparisons between humans and other animals, and will facilitate studies of human neurological and psychiatric diseases.

The innate immune sensor Toll-like receptor 4 controls inflammatory gene expression. Here the authors identify a network of positive and negative feedback loops involving the transcription factor C/EBPd and ubiquitin ligase substrate adaptor FBXW7a that regulate TLR4 levels and inflammatory signalling.

The genome of the gibbon, a tree-dwelling ape from Asia positioned between Old World monkeys and the great apes, is presented, providing insights into the evolutionary history of gibbon species and their accelerated karyotypes, as well as evidence for selection of genes such as those for forelimb development and connective tissue that may be important for locomotion through trees.

Iris Heid, Gonçalo Abecasis, Sudha Iyengar and colleagues report the results of a large genome-wide association meta-analysis of macular degeneration based on over 43,000 subjects. They identify 16 new risk loci, including some very rare coding variants.

Analyzing and integrating a broad range of behavioral phenotypes enables prediction of underlying genetic mutations in mouse models of Huntington's disease.

Research in the early days of chemical biology was mostly limited to the application of chemical tools to model cell lines grown in incubators. Now, discoveries are being made in more physiologically relevant systems, from tissues to organisms, using precisely targeted molecules. The 2023 Chemical Biology & Physiology meeting (in Portland, Oregon) discussed the latest advances in the field, with research from around the globe demonstrating that the transition to making discoveries at the chemical biology–physiology interface is happening now.

MetaSTAAR enables functionally informed rare variant association analysis in biobank-scale cohorts using an efficient, sparse matrix approach for summary statistic storage.

Structural variants in more than 17,000 human genomes are mapped and characterized using whole-genome sequencing, showing how this type of variation contributes to rare deleterious coding and noncoding alleles.

Using the GTEx data and others, a comprehensive analysis of adenosine-to-inosine RNA editing in mammals is presented; targets of the various ADAR enzymes are identified, as are several potential regulators of editing, such as AIMP2.

Multiple transcriptome approaches, including single-cell sequencing, demonstrate that escape from X chromosome inactivation is widespread and occasionally variable between cells, chromosomes, and tissues, resulting in sex-biased expression of at least 60 genes and potentially contributing to sex-specific differences in health and disease.

The authors show that rare genetic variants contribute to large gene expression changes across diverse human tissues and provide an integrative method for interpretation of rare variants in individual genomes.

Kathleen Millen and colleagues report that mutations in FOXC1 lead to cerebellar defects and contribute to Dandy-Walker malformation in humans.

Kathy Sivils and colleagues report results of a large-scale association study of Sjögren's syndrome, a common autoimmune disease. They confirm strong associations with the HLA region and establish genome-wide significant associations at several non-HLA loci implicated in both innate and adaptive immunity.

STAAR is a powerful rare variant association test that incorporates variant functional categories and complementary functional annotations using a dynamic weighting scheme based on annotation principal components. STAAR accounts for population structure and relatedness and is scalable for analyzing large whole-genome sequencing studies.

Roger Milne and colleagues conduct a genome-wide association study for estrogen receptor (ER)-negative breast cancer combined with BRCA1 mutation carriers in a large cohort. They identify ten new risk variants and find high genetic correlation between breast cancer risk for BRCA1 mutation carriers and risk of ER-negative breast cancer in the general population.

Association analysis identifies 65 new breast cancer risk loci, predicts target genes for known risk loci and demonstrates a strong overlap with somatic driver genes in breast tumours.

Two mutations in the gene DCHS1 are shown to cause non-syndromic mitral valve prolapse (MVP), a common cardiac valve disease; understanding the role of DCHS1 in mitral valve development and MVP pathogenesis holds therapeutic potential.

The polarization resulting from electron scattering in a stellar atmosphere has been detected towards the rapidly spinning star Regulus. Deformation of the star from spherical allows this effect to be seen, fulfilling a prediction from around 50 years ago.

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.

An integrated analysis of over 100 single-cell and single-nucleus transcriptomics studies illustrates severe acute respiratory syndrome coronavirus 2 viral entry gene coexpression patterns across different human tissues, and shows association of age, smoking status and sex with viral entry gene expression in respiratory cell populations.