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Response to anti-PD-1 in patients with hepatocellular carcinoma is associated with clonal expansion of intratumoral CXCL13⁺ CD4⁺ helper T cells and effector-like CD8⁺ T cells, and local dendritic cells enriched in expression of maturation and regulatory molecules help facilitate CD8⁺ T cell differentiation.

Geospatial estimates of the prevalence of anemia in women of reproductive age across 82 low-income and middle-income countries reveals considerable heterogeneity and inequality at national and subnational levels, with few countries on track to meet the WHO Global Nutrition Targets by 2030.

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

A scalable pipeline MARQO resolves the multiparametric cellular and spatial data in responders to immune checkpoint blockade therapy relative to non-responders.

What is the state of trust in scientists around the world? To answer this question, the authors surveyed 71,922 respondents in 68 countries and found that trust in scientists is moderately high.

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 BioDIGS project is a nationwide initiative involving students, researchers and educators across more than 40 research and teaching institutions. Participants lead sample collection, computational analysis and results interpretation to understand the relationships between the soil microbiome, environment and health.

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.

Climate change is shifting species distribution globally. Here, the authors track four decades of changes in the thermal affinity of 1,817 marine species across European seas, showing that most communities have responded to ongoing ocean warming via increases of warm-water species or decreases of cold-water species.

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.

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.

Genome-wide association and fine-mapping analyses in ancestrally diverse populations implicate candidate causal genes and mechanisms underlying type 2 diabetes. Trans-ancestry genetic risk scores enhance transferability across populations.

Exome-sequencing analyses of a large cohort of patients with type 2 diabetes and control individuals without diabetes from five ancestries are used to identify gene-level associations of rare variants that are associated with type 2 diabetes.

Antibody Mediated Prevention (AMP) trials showed that the broadly neutralizing antibody VRC01 could prevent some HIV-1 acquisitions. Here the authors use VRC01 levels and the sensitivity of each acquired HIV virus to predict viral loads in the AMP studies and show that VRC01 influenced viral loads, though potency was lower in vivo than expected.

Cancer genetics has benefited from the advent of next generation sequencing, yet a comparison of sequencing and analysis techniques is lacking. Here, the authors sequence a normal-tumour pair and perform data analysis at multiple institutes and highlight some of the pitfalls associated with the different methods.

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.

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.

Benchmarking of tumor subclonal reconstruction algorithms finds that interalgorithm variability overwhelms intertumor variability and identifies key quality metrics.

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.

Systematic characterization of longitudinal tau variability in human Alzheimer’s disease using an unbiased subtyping algorithm reveals four trajectories of tau deposition with distinct clinical features.

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.

Rhabdomyosarcomas are tumours blocked in myogenic differentiation, which despite the expression of master muscle regulatory factors, including MYOD, are unable to differentiate. Here, the authors show that SNAI2 is upregulated by MYOD through super enhancers, binds to MYOD target enhancers, and arrests differentiation.

By integrating the serum concentration of a broadly neutralizing antibody (bNAb) with its in vitro 80% inhibitory concentration, the PT₈₀ biomarker may be used to guide target levels of bNAbs for effective prevention of HIV-1 acquisition.

Hepatocellular carcinoma (HCC) generally develops as a consequence of underlying liver disease, most commonly viral hepatitis. Currently, surgery remains the treatment of choice for HCC; however, due to underlying liver disease only a minority of those affected are candidates for resection, and access to transplantation is limited by organ availability. The authors of this review discuss when liver resection, nonsurgical HCC treatment and management before liver transplantation should be considered, and the applications of nonsystemic therapies.

The tau protein is theorized to spread transneuronally in Alzheimers disease, though this theory remains unproven in humans. Our simulations of epidemic-like protein spreading across human brain networks support this theory, and suggest the spreading dynamics are modified by β-amyloid

Drug and target discovery for advanced liver disease are hampered by a lack of suitable models for clinical translation. Here the authors present a human liver cell-based system modeling a clinical prognostic signature allowing to propose nizatidine for treatment of advanced liver fibrosis and hepatocellular carcinoma prevention.

Vein of Galen malformations (VOGMs) are severe congenital brain arteriovenous malformations. Here the authors work to elucidate the pathogenesis of VOGMs by performing an integrated analysis of 310 VOGM proband family exomes and 336,326 human cerebrovasculature single-cell transcriptomes to identify mutations of key signaling regulators.

Genetic variants at multiple loci of chr5p15.33 have been associated with susceptibility to numerous cancers. Here the authors show that the association of one of these loci may be explained by a variant, rs36115365, influencing telomerase reverse transcriptase (TERT) expression via ZNF148.

The monarch butterfly, well known for its spectacular annual migration across North America, is shown by genome sequencing of monarchs from around the world to have been ancestrally migratory and to have dispersed out of North America to occupy its current broad distribution; the authors also discovered signatures of selection associated with migration within loci implicated in flight muscle function, leading to greater flight efficiency.

Immune-mediated selection pressures impact the clonal evolution of tumours. Here, in hepatocellular carcinoma the authors map spatio-temporal interactions between tumor and immune cells, highlighting the regulatory substrate of intra-tumoural heterogeneity that correlates with regional adaptive immune responses.

Luis Pérez-Jurado, Stephen Chanock and colleagues detect clonal chromosomal abnormalities in peripheral blood or buccal samples from individuals in the general population. They show that the frequency of such events increases with age and is associated with elevated risk of developing subsequent hematological cancers.

Alzheimer’s disease has been associated with increased structural brain aging. Here the authors describe a model that predicts brain aging from resting state functional connectivity data, and demonstrate this is accelerated in individuals with pre-clinical familial Alzheimer’s disease.

This paper describes immunocompromised rag2 mutant zebrafish, which allow efficient and robust cell transplantations in adult zebrafish, thereby facilitating stem cell, cancer and regeneration research.

Recombination contributes to HIV evolution in patients, but its identification can be difficult. Here, the authors develop a computational tool called RAPR to track recombination in patients, identify recombination hot spots, and show contribution of recombination to antibody escape.

Many animals communicate through gestures, some caterpillars use scraping and drumming signals to ward off unwanted neighbours. Here, Scottet al. demonstrate that "leg-like" structures used by some caterpillar species to communicate evolved from legs that their ancestors used to walk.

Direct visualisation of heterogeneous cell populations in live animals has been challenging. Here, the authors optimize cell transplantation into optically clear immune-deficient zebrafish, and use intravital imaging to track and to assess functional diversity of individual cancer cells in vivo.

Progressive diseases tend to be heterogeneous in their underlying aetiology mechanism, disease manifestation, and disease time course. Here, Young and colleagues devise a computational method to account for both phenotypic heterogeneity and temporal heterogeneity, and demonstrate it using two neurodegenerative disease cohorts.

Alzheimer’s disease is heterogeneous in its neuroimaging and clinical phenotypes. Here the authors present a semi-supervised deep learning method, Smile-GAN, to show four neurodegenerative patterns and two progression pathways providing prognostic and clinical information.

Intrahepatic cholangiocarcinoma is an aggressive cancer of the bile duct with few treatment options and a below 10% five-year survival rate. Here Sia et al. show a novel FGFR2–PPHLN1 fusion and ARAFmutations that may represent future potential therapeutic targets.

The interplay between amyloid and tau pathology in Alzheimer’s disease is still not well understood. Here, the authors show that amyloid-related increased in soluble p-tau is related to subsequent accumulation of tau aggregates and cognitive decline in early stage of the disease.

Whole genomes of 185 atypical enteropathogenic Escherichia coli (aEPEC) isolates reveal 30 LEE (locus of enterocyte effacement) subtypes in 3 major lineages, varying in insertion site preference and their complement of non-LEE encoded effector genes.

Gordon Dougan and colleagues report whole-genome sequencing of a global collection of 179 Salmonella Typhimurium isolates, including 129 diverse sub-Saharan African isolates associated with invasive disease. They determine the phylogenetic structure of invasive Salmonella Typhimurium in sub-Saharan Africa and find that the majority are from two closely related highly conserved lineages, which emerged in the last 60 years in close temporal association with the current HIV epidemic.

Soybean is an important crop plant, providing seed protein and oil and fixing atmospheric nitrogen through symbioses with soil-borne microorganisms. Using a whole-genome shotgun approach, its 1.1-gigabase genome is now sequenced and integrated with physical and high-density genetic maps to create a chromosome-scale draft sequence assembly.