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In this Primer, Plikus and colleagues review the epidemiology, pathophysiology and diagnosis of androgenetic alopecia, an inherited hair loss condition that affects both men and women, and highlight the current and emerging treatment and management options.

Passive immunisation for respiratory syncytial virus for infants is recommended by the World Health Organization but products currently available have limited duration of protection. Here, the authors investigate the age distribution of infant hospitalisation for respiratory syncytial virus to inform optimal timing of immunisation.

Steele et al. use single-cell RNA sequencing and spatial transcriptomics to provide an atlas of adult human skin fibroblasts in healthy and diseased human skin.

Integrative analyses of transcriptome and whole-genome sequencing data for 1,188 tumours across 27 types of cancer are used to provide a comprehensive catalogue of RNA-level alterations in cancer.

A purely organic crystalline two-dimensional mechanically interlocked polymer comprising [c2]daisy chain units forms via preorganized crystallization and thiol–ene click chemistry. This polymer network can be exfoliated to give nanosheets with a 47-fold stiffness enhancement relative to the bulk parent.

This study used fine-mapping to analyze genetic regions associated with bipolar disorder, identifying specific risk genes and providing new insights into the biology of the condition that may guide future research and treatment approaches.

PIEZO1 is critical in numerous physiological processes, but monitoring its activity and localization in cells can be challenging. Here, the authors present a chemogenetic platform to visualize endogenous human PIEZO1 localization and activity in native cellular conditions, expanding the knowledge on mechanotransduction across single cells and tissue organoids.

Phylogenomic analysis of 7,923 angiosperm species using a standardized set of 353 nuclear genes produced an angiosperm tree of life dated with 200 fossil calibrations, providing key insights into evolutionary relationships and diversification.

Analyses of 2,658 whole genomes across 38 types of cancer identify the contribution of non-coding point mutations and structural variants to driving cancer.

With the generation of large pan-cancer whole-exome and whole-genome sequencing projects, a question remains about how comparable these datasets are. Here, using The Cancer Genome Atlas samples analysed as part of the Pan-Cancer Analysis of Whole Genomes project, the authors explore the concordance of mutations called by whole exome sequencing and whole genome sequencing techniques.

The flagship paper of the ICGC/TCGA Pan-Cancer Analysis of Whole Genomes Consortium describes the generation of the integrative analyses of 2,658 cancer whole genomes and their matching normal tissues across 38 tumour types, the structures for international data sharing and standardized analyses, and the main scientific findings from across the consortium studies.

The authors present SVclone, a computational method for inferring the cancer cell fraction of structural variants from whole-genome sequencing data.

Many tumours exhibit hypoxia (low oxygen) and hypoxic tumours often respond poorly to therapy. Here, the authors quantify hypoxia in 1188 tumours from 27 cancer types, showing elevated hypoxia links to increased mutational load, directing evolutionary trajectories.

Understanding deregulation of biological pathways in cancer can provide insight into disease etiology and potential therapies. Here, as part of the PanCancer Analysis of Whole Genomes (PCAWG) consortium, the authors present pathway and network analysis of 2583 whole cancer genomes from 27 tumour types.

Analysis of cancer genome sequencing data has enabled the discovery of driver mutations. Here, as part of the ICGC/TCGA Pan-Cancer Analysis of Whole Genomes (PCAWG) Consortium the authors present DriverPower, a software package that identifies coding and non-coding driver mutations within cancer whole genomes via consideration of mutational burden and functional impact evidence.

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.

Multi-omics datasets pose major challenges to data interpretation and hypothesis generation owing to their high-dimensional molecular profiles. Here, the authors develop ActivePathways method, which uses data fusion techniques for integrative pathway analysis of multi-omics data and candidate gene discovery.

In this study the authors consider the structural variants (SVs) present within cancer cases of the ICGC/TCGA Pan-Cancer Analysis of Whole Genomes (PCAWG) Consortium. They report hundreds of genes, including known cancer-associated genes for which the nearby presence of a SV breakpoint is associated with altered expression.

Cancers evolve as they progress under differing selective pressures. Here, as part of the ICGC/TCGA Pan-Cancer Analysis of Whole Genomes (PCAWG) Consortium, the authors present the method TrackSig the estimates evolutionary trajectories of somatic mutational processes from single bulk tumour data.

Whole-genome sequencing data for 2,778 cancer samples from 2,658 unique donors across 38 cancer types is used to reconstruct the evolutionary history of cancer, revealing that driver mutations can precede diagnosis by several years to decades.

An analysis of 2,954 genomes from 38 cancer subtypes identified 19,166 retrotransposition events in 35% of samples. Aberrant LINE-1 retrotranspositions can lead to the deletion of tumor-suppressor genes as well as the amplification of oncogenes.

In somatic cells the mechanisms maintaining the chromosome ends are normally inactivated; however, cancer cells can re-activate these pathways to support continuous growth. Here, the authors characterize the telomeric landscapes across tumour types and identify genomic alterations associated with different telomere maintenance mechanisms.

Viral pathogen load in cancer genomes is estimated through analysis of sequencing data from 2,656 tumors across 35 cancer types using multiple pathogen-detection pipelines, identifying viruses in 382 genomic and 68 transcriptome datasets.

The characterization of 4,645 whole-genome and 19,184 exome sequences, covering most types of cancer, identifies 81 single-base substitution, doublet-base substitution and small-insertion-and-deletion mutational signatures, providing a systematic overview of the mutational processes that contribute to cancer development.

There’s an emerging body of evidence to show how biological sex impacts cancer incidence, treatment and underlying biology. Here, using a large pan-cancer dataset, the authors further highlight how sex differences shape the cancer genome.

Whole-genome sequencing data from more than 2,500 cancers of 38 tumour types reveal 16 signatures that can be used to classify somatic structural variants, highlighting the diversity of genomic rearrangements in cancer.

A pan-cancer genomic analysis reports the effects of structural variations on chromatin domains (TADs). Most TAD disruptions do not result in appreciable changes in expression of nearby genes.

Middle-aged individuals are more susceptible to obesity, but the mechanisms are unclear. Here, the authors show that extracellular vesicles from adipose progenitor cells in middle-aged individuals lack miR-145-5p, driving inflammation, and that restoring miR-145-5p could prevent midlife obesity.

Some cancer patients first present with metastases where the location of the primary is unidentified; these are difficult to treat. In this study, using machine learning, the authors develop a method to determine the tissue of origin of a cancer based on whole sequencing data.

Cervical cancer remains a significant public health problem in many regions. Here, the authors perform a proteogenomic analysis of cervical cancer in Chinese patients; they reveal proteomic subgroups associated with clinical and biological features, and a potential biomarker of response to radiotherapy.

Similarities in cancers can be studied to interrogate their etiology. Here, the authors use genome-wide association study summary statistics from six cancer types based on 296,215 cases and 301,319 controls of European ancestry, showing that solid tumours arising from different tissues share a degree of common germline genetic basis.

Brain neural stem cell (NSC) and vessel-forming endothelial cell (EC) communication is vital. Here, the authors find that human ECs boost human adult NSCs (type B cells) via Notch, show EC-type B interaction in human brain, and identify human type B markers.

The evolutionary reasons for the variation in silicon concentrations across plant families remain unclear. This paper provides new evidence that silicon variation is closely linked to global and long-term climate change, suggesting temperature could have driven the evolution of plant silicification.

Sun et al. report human lifespan changes in the brain’s functional connectome in 33,250 individuals, which highlights critical growth milestones and distinct maturation patterns and offers a normative reference for development, aging and diseases.

Oestrogen negative breast cancer is associated with a poor prognosis. In this study, the authors perform a meta-analysis of 11 breast cancer genome-wide association studies and identify four new loci associated with oestrogen negative breast cancer risk. These findings may aid in stratifying patients in the clinic.

Temporal multi-omic analysis of tissues from rats undergoing up to eight weeks of endurance exercise training reveals widespread shared, tissue-specific and sex-specific changes, including immune, metabolic, stress response and mitochondrial pathways.

The immune-checkpoint molecule TIM-3 regulates microglial homeostasis, and its microglial-specific deletion reduced cognitive impairment in a mouse model of Alzheimer’s disease.

Human fibroblasts are reprogrammed to generate blastocyst-like structures called iBlastoids, which recapitulate aspects of embryo implantation.

Nguyen et al. identify TDP-43 and METTL3 as key regulators of disrupted RNA splicing in Huntington’s disease, offering insight into how TDP-43 mislocalization and aberrant m6A RNA modification and localization relate to disease pathogenesis.

Reduced glomerular filtration rate (eGFR) is a hallmark of chronic kidney disease. Here, Pattaro et al. conduct a meta-analysis to discover several new loci associated with variation in eGFR and find that genes associated with eGFR loci often encode proteins potentially related to kidney development.

The phosphoethanolamine transferase modifies lipopolysaccharide structure and confers antibiotic resistance on Gram-negative bacteria. Here the authors reveal how the membrane lipid modulates the conformational transition of this important enzyme.

Alterations in proteins within nuclear compartments often lead to changes in chromosomal architecture. Here, using acute targeted protein degradation, the authors reveal that the nuclear complex protein Matrin3 directly mediates differentiation through stabilizing chromatin loop domain interactions.

Studies have shown that breast cancer prognosis is hereditary. Here the authors show that a genetic variant in CCL20, a chemokine ligand involved in immune response, is significantly associated with breast cancer survival and may therefore represent an important therapeutic or prognostic target.