Publications by authors named "Sakaue S"

Aberrant immune responses to viral pathogens contribute to pathogenesis, but our understanding of pathological immune responses caused by viruses within the human virome, especially at a population scale, remains limited. We analyzed whole-genome sequencing datasets of 6,321 Japanese individuals, including patients with autoimmune diseases (psoriasis vulgaris, rheumatoid arthritis (RA), systemic lupus erythematosus (SLE), pulmonary alveolar proteinosis (PAP) or multiple sclerosis) and coronavirus disease 2019 (COVID-19), or healthy controls. We systematically quantified two constituents of the blood DNA virome, endogenous HHV-6 (eHHV-6) and anellovirus.

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The tripartite ancestral structure is a recently proposed model for the genetic origin of modern Japanese, comprising indigenous Jomon hunter-gatherers and two additional continental ancestors from Northeast Asia and East Asia. To investigate the impact of the tripartite structure on genetic and phenotypic variation today, we conducted biobank-scale analyses by merging Biobank Japan (BBJ; n = 171,287) with ancient Japanese and Eurasian genomes (n = 22). We demonstrate the applicability of the tripartite model to Japanese populations throughout the archipelago, with an extremely strong correlation between Jomon ancestry and genomic variation among individuals.

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Rationale: Rheumatoid arthritis (RA) has been implicated in interstitial lung disease (ILD) as majority of studies have been comprised of patients with known RA. However, it remains unclear whether an underlying risk for RA in combination with genetic risk for pulmonary fibrosis is associated with radiological markers of early lung injury and fibrosis in broader population samples.

Objective: Determine whether genetic and serological biomarkers of RA risk in combination with the (rs35705950) risk allele (T) are associated with interstitial lung abnormalities (ILA) on computed tomography (CT) scans.

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Disease risk alleles influence the composition of cells present in the body, but modeling genetic effects on the cell states revealed by single-cell profiling is difficult because variant-associated states may reflect diverse combinations of the profiled cell features that are challenging to predefine. We introduce Genotype-Neighborhood Associations (GeNA), a statistical tool to identify cell-state abundance quantitative trait loci (csaQTLs) in high-dimensional single-cell datasets. Instead of testing associations to predefined cell states, GeNA flexibly identifies the cell states whose abundance is most associated with genetic variants.

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Article Synopsis
  • The study investigates how genetic factors regulate protein expression using protein quantitative trait loci (pQTLs) and highlights differences from traditional mRNA expression studies (eQTLs).
  • Analyzing data from over 4,000 samples, researchers found that fine-mapped pQTLs are linked to missense variants and show distinct mechanisms from eQTLs, indicating different regulatory influences.
  • The research reveals a negative correlation between ABO gene mRNA and protein levels due to genetic linkage, showcasing the complexities in the relationship between these expression types.
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Genetic variation in the human leukocyte antigen (HLA) loci is associated with risk of immune-mediated diseases, but the molecular effects of HLA polymorphism are unclear. Here we examined the effects of HLA genetic variation on the expression of 2940 plasma proteins across 45,330 Europeans in the UK Biobank, with replication analyses across multiple ancestry groups. We detected 504 proteins affected by HLA variants (HLA-pQTL), including widespread trans effects by autoimmune disease risk alleles.

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Mesoporous silica nanoparticles (MSNs) are physically and chemically stable inorganic nanomaterials that have been attracting much attention as carriers for drug delivery systems in the field of nanomedicine. In the present study, we investigated the potential of MSN vaccines that incorporate antigen peptides for use in cancer immunotherapy. In vitro experiments demonstrated that fluorescently labeled MSNs accumulated in a line of mouse dendritic cells (DC2.

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Rheumatoid arthritis (RA) is an autoimmune disease involving antigen-specific T and B cells. Here, we perform single-cell RNA and repertoire sequencing on paired synovial tissue and blood samples from 12 seropositive RA patients. We identify clonally expanded CD4 + T cells, including CCL5+ cells and T peripheral helper (Tph) cells, which show a prominent transcriptomic signature of recent activation and effector function.

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Synovial tissue inflammation is a hallmark of rheumatoid arthritis (RA). Recent work has identified prominent pathogenic cell states in inflamed RA synovial tissue, such as T peripheral helper cells; however, the epigenetic regulation of these states has yet to be defined. Here, we examine genome-wide open chromatin at single-cell resolution in 30 synovial tissue samples, including 12 samples with transcriptional data in multimodal experiments.

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Article Synopsis
  • Developed a new method called SCENT for mapping enhancer-gene relationships using single-cell data to improve understanding of genetic influences on diseases.
  • Successfully applied SCENT to over 120,000 single cells, creating 23 detailed enhancer-gene maps specific to different cell types.
  • These maps revealed likely causal genes associated with various diseases, helping to connect genetic variants to their functional roles in human health.
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  • - A new multi-ancestry genome-wide association study (GWAS) of major depression (MD) analyzed data from 88,316 cases and 902,757 controls, representing various ancestries including African, East Asian, South Asian, and Hispanic/Latin American.
  • - The study discovered 53 novel genetic loci significantly linked to MD, with fewer existing European ancestry loci proving relevant to other ancestry groups.
  • - A transcriptome-wide association study in this research identified 205 new genes associated with MD, highlighting the importance of diverse ancestry in genetic research for better understanding and finding relevant genes.
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The human leukocyte antigen (HLA) locus plays a critical role in complex traits spanning autoimmune and infectious diseases, transplantation and cancer. While coding variation in HLA genes has been extensively documented, regulatory genetic variation modulating HLA expression levels has not been comprehensively investigated. Here we mapped expression quantitative trait loci (eQTLs) for classical HLA genes across 1,073 individuals and 1,131,414 single cells from three tissues.

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Article Synopsis
  • Autoimmune diseases like rheumatoid arthritis involve the immune system mistakenly attacking the body's own cells, highlighting the need for a better understanding of how noncoding genetic variants contribute to these conditions.
  • Researchers analyzed over 28,000 cells from the inflamed tissue of 12 donors, combining RNA sequencing and chromatin accessibility data to investigate the regulatory elements linked to gene expression patterns in immune cells.
  • They found that certain dynamic regions of accessible chromatin were significantly associated with genetic risk for 14 autoimmune diseases, suggesting these regions could help pinpoint specific cell states that play critical roles in disease development.
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Purpose: To confirm the hypothesis that brain white matter damage is involved in the pathogenesis and disease progression of Langerhans cell histiocytosis (LCH)-associated neurodegenerative disease (ND), we aimed to analyze pediatric patients with LCH using diffusion tensor imaging (DTI).

Methods: We enrolled 33 patients with LCH and obtained 33 DTI datasets. Using DTI-based tractography, fractional anisotropy (FA), apparent diffusion coefficient (ADC), axial diffusivity (AD), and radial diffusivity (RD) were measured in the cerebral and cerebellar white matter tracts.

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Background: The aim of this study was to evaluate the correlation among mutations in cancer-related genes, clinicopathologic features, and clinical outcome in classical papillary thyroid carcinoma (PTC).

Patients And Methods: A total of 130 patients with classical PTC who underwent curative surgery between April 2012 and June 2023 at Hokuto Hospital were included. Mutations in targeted regions of 160 cancer-related genes were detected by next-generation sequencing (NGS)-based cancer panel testing.

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Upper airway infections caused by anaerobic bacteria, including pharyngitis and tonsillitis, are a common cause of septic thrombosis (Lemierre's syndrome). Although otitis media rarely progresses to systemic infection, an abscess surrounding the middle ear can affect the central nervous system. was originally considered a non-pathogenic aerobic bacterium but has subsequently been reported to cause bacteremia and brain abscesses.

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The human leukocyte antigen (HLA) locus is associated with more complex diseases than any other locus in the human genome. In many diseases, HLA explains more heritability than all other known loci combined. In silico HLA imputation methods enable rapid and accurate estimation of HLA alleles in the millions of individuals that are already genotyped on microarrays.

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A 72-year-old Japanese man with a 4-month history of hoarseness and 1-week history of difficulty breathing was admitted to our department. He underwent right total nephrectomy for primary clear cell-type renal cell carcinoma (RCC) 6 years ago and left partial nephrectomy for the metastasis 4 years ago. Flexible laryngeal fiberscope examination revealed bilateral subglottic stenosis without obvious mucosal lesions.

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Synovial tissue inflammation is the hallmark of rheumatoid arthritis (RA). Recent work has identified prominent pathogenic cell states in inflamed RA synovial tissue, such as T peripheral helper cells; however, the epigenetic regulation of these states has yet to be defined. We measured genome-wide open chromatin at single cell resolution from 30 synovial tissue samples, including 12 samples with transcriptional data in multimodal experiments.

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Rheumatoid arthritis (RA) is an autoimmune disease initiated by antigen-specific T cells and B cells, which promote synovial inflammation through a complex set of interactions with innate immune and stromal cells. To better understand the phenotypes and clonal relationships of synovial T and B cells, we performed single-cell RNA and repertoire sequencing on paired synovial tissue and peripheral blood samples from 12 donors with seropositive RA ranging from early to chronic disease. Paired transcriptomic-repertoire analyses highlighted 3 clonally distinct CD4 T cells populations that were enriched in RA synovium: T peripheral helper (Tph) and T follicular helper (Tfh) cells, CCL5+ T cells, and T regulatory cells (Tregs).

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The human leukocyte antigen (HLA) locus plays a critical role in complex traits spanning autoimmune and infectious diseases, transplantation, and cancer. While coding variation in genes has been extensively documented, regulatory genetic variation modulating expression levels has not been comprehensively investigated. Here, we mapped expression quantitative trait loci (eQTLs) for classical genes across 1,073 individuals and 1,131,414 single cells from three tissues, using personalized reference genomes to mitigate technical confounding.

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