Nature Communications

Measles resurgence in high-income countries that previously achieved elimination reveals a critical surveillance failure: current systems rely on county-level aggregates that obscure fine-scale clustering where outbreaks originate. We assembled the nationwide multiscale vaccination database spanning 45 US states (2013-2025), encompassing over 50,000 schools, 13,000 districts, and 3,000 counties. We developed a gravity-based transmission framework and demonstrate that school-level effective repro...

Transcription factors play key roles in cellular biology. Their genomic binding events are enriched at disease- and trait-associated genetic risk loci in particular cellular contexts. To examine this phenomenon in depth, we constructed a PU.1 (SPI1) binding atlas by uniformly processing 260 PU.1 ChIP-seq datasets spanning many immune cell types. Comparison of ChIP-seq peaks across eight major immune cell types identifies shared and cell type-specific PU.1 binding events. DNA sequence analyses re...

Population-based studies of circulating blood proteins have provided profound insights into human biology. However, short-lived changes often remained undetected. To address this, we performed a comprehensive longitudinal dried blood spot (DBS) self-sampling study in 808 young adults of the BAMSE cohort during 2020-2022. We profiled serological, autoimmune, and proteomic phenotypes in relation to SARS-CoV-2 exposures (infection, vaccination), physiological traits, genetic variation, and blood co...

Inflammatory resolution is essential for tissue health, yet its dynamics remain difficult to study in humans. Menstruation is a recurrent, non-pathological inflammatory process that provides a natural window into inflammation and repair. We developed and validated a standardized menstrual sampling and RNA-seq workflow, analyzing more than 1,000 samples from over 300 individuals. We show that menstrual transcriptomes are dominated by two major biological confounders: heterogeneous tissue composit...

AO_SCPLOWBSTRACTC_SCPLOWInfluenza A subclade K viruses caused high infection rates in the 2025/2026 Northern Hemisphere season, raising concerns about antigenic drift and reduced vaccine effectiveness. We measured antibody responses in matched human pre- and post-vaccination sera against a vaccine-like as well as subclade K isolates. Pre-existing immunity to subclade K variants was noted with seasonal influenza vaccination boosting titers two-fold against subclade K and three-fold against the va...

AbstractGenome-wide studies (GWAS) on asthma have identified nearly 200 genomic loci. However, the underlying mechanisms remain mostly elusive. While functional profiling of blood immune cell types has helped interpret asthma GWAS signals, high-resolution functional genomic data of lung immune cells, which differ from circulating immune cells, are lacking. We thus profiled single-cell multi-omics (RNA-seq and ATAC-seq) on lymphocytes of lung and spleen tissues from 9 donors. Cross-tissue compari...

BackgroundInfluenza vaccination and bacterial colonization both shape immunity in the respiratory tract, yet their combined impact on the human lung mucosa remains poorly understood. Secondary bacterial pneumonia following influenza infection is a leading cause of mortality, underscoring the need to define how vaccines and microbes intersect at the airway interface. MethodsUsing the Experimental Human Pneumococcal Challenge (EHPC) model, we examined how intramuscular inactivated (TIV) and nasal...

Why do some individuals develop mild COVID-19 while others progress to severe disease remains a central challenge in SARS-CoV-2 immunology. In this study, we leveraged the BACO Cohort - a unique historical cohort of immunologically naive, hospitalized COVID-19 patients from the first pandemic wave - to investigate early immune determinants of clinical disease trajectories. Integrating bulk RNA-seq, Olink proteomics, and systems serology, we identified two fundamentally distinct immune trajectori...

Early cancer detection substantially improves patient survival, yet conventional screening methods are directed at single anatomical sites and inadequately screen 45.5% of cases. Cell-free RNA (cfRNA) from blood offers a promising, non-invasive avenue for early cancer detection, reflecting real-time transcriptional activity from tumors. However, most RNA-seq pipelines focus exclusively on annotated genes, ignoring the 98% of the human genome comprising unannotated regions including noncoding RNA...

We examined whether the recent emergence of influenza A(H3N2) subclade K, associated with an unusually early influenza season in the Northern hemisphere, was accompanied by a reduction in human population immunity. Using virus neutralisation assays on pre-epidemic human sera collected in May 2025, we found evidence of moderate antigenic drift. Further, vaccines used in the 2024/2025 season induced cross-neutralising immunity. These findings provide timely insight for interpreting recent influenz...

BackgroundSinonasal malignancies frequently present with symptoms overlapping chronic inflammatory conditions such as chronic rhinosinusitis (CRS), complicating early detection and delaying treatment. A fast, scalable, non-invasive approach capable of resolving immune and epithelial cell states across inflammatory and malignant disease from routine nasal swabs could substantially improve clinical screening, leading to the initiation of appropriate treatment. MethodsWe developed a deep learning-...

Proteogenomic studies integrating genetic, molecular, and phenotypic data have transformed target discovery, yet remain heavily biased toward European populations. Here, we present a large-scale proteogenomic atlas in a non-European population, analysing 7,289 plasma proteins profiled by SomaScan v4.1 in 3,965 Chinese adults. Genome-wide association analyses identified 3,212 protein quantitative trait loci (pQTLs), including 1,092 proteins with a cis-pQTL. Integrating these data with East Asian ...

BACKGROUNDUnderstanding SARS-CoV-2 antibody dynamics is critical for pandemic preparedness, particularly where population immunity has developed through high infection rates with minimal vaccination. Whether predominantly asymptomatic infections confer protective immunity and which biomarkers best predict protection in resource-limited settings remain unclear. METHODSWe conducted a household cohort study in The Gambia over 15 months (March 2021-June 2022) during Delta and Omicron waves, with we...

Cutaneous leishmaniasis (CL) is a skin disease caused by Leishmania infection, for which no licensed human vaccine exists. Protective immunity is largely T cell-mediated and depends on antigen presentation by MHC molecules, yet the naturally presented epitopes during human disease remain poorly defined. To address this gap, we performed mass spectrometry-based immunopeptidomics on lesional biopsies from 27 Ethiopian CL patients spanning the full clinical spectrum. We newly identified 333 MHC-I a...

The standard treatment for stage I lung adenocarcinoma is surgical resection, in most cases without additional systemic adjuvant treatment. A significant proportion of stage I cases recur with a less than 50% 5-year survival rate. There are clinical data suggesting that adjuvant treatment may improve survival in such recurrent cases. However, previously evaluated predictors such as the IASLC grading system from histological sections and transcriptomic profiles have not been sufficiently accurate...

Functional interpretation is essential for understanding how genetic variants contribute to complex traits. Here, we identified and characterized regulatory variants in CD4+ T cells collected from 362 donors. We integrated molecular QTL mapping from single-cell RNA-seq profiles and chromatin accessibility with predicted variant effects from a deep learning model trained on chromatin accessibility data. We identified molecular features and transcription factor binding mechanisms underlying varian...

Tumour typing from whole-genome sequencing is increasingly accurate, yet molecular subtyping from somatic variants remains challenging because of tumour heterogeneity and inconsistent clinical annotations. Here, we present Mutation-Attention Dual-Task (MuAt2), a Transformer model that jointly classifies histological tumour types and subtypes directly from somatic single-nucleotide variants, indels and structural variants. MuAt2 leverages encoders pre-trained on 2,587 pan-cancer whole genomes, an...

In November 2024, a highly divergent BA.3-related SARS-CoV-2 lineage, designated BA.3.2, was detected in South Africa, marking the first appearance of a BA.3-derived lineage in over two years. Phylogenetic reconstruction places BA.3.2 on an extended branch descending from ancestral BA.3, with no intermediate genomes detected, consistent with a prolonged period of unsampled or isolated evolution. Molecular clock analyses indicate accelerated divergence characteristic of a saltation event, while p...

Mitochondrial heteroplasmic variant has been increasingly recognized as a potential contributor to common complex diseases, yet its relationship with cardiometabolic disorders (CMDs) remains poorly understood. Leveraging deep whole-genome sequencing data from 16,882 participants across six multi-ancestry TOPMed cohorts, we systematically evaluated the associations between rare heteroplasmic variants and eight CMD traits, including body mass index (BMI), obesity, blood pressure, hypertension, blo...

Alzheimers disease (AD) is marked by hallmark neuropathological changes in the brain. However, its upstream genetic determinants, beyond the central nervous system (CNS), remain largely unexplored. To that extent, we integrated human genomic data with cross-tissue and single-cell analyses across up to 40 peripheral tissues and 100 brain regions. We observed limited genetic enrichment in the CNS, with brain-resident microglia emerging as the sole enriched cell type. Instead, AD risk loci were pre...