14662 results for "PLOS+ONE+Pennsylvania+German+ACS+language+code+pdc+open+access+study"

in 26.56 milliseconds.

• Germline DNA Methylation Associated with Breast Cancer Predisposition

  Understanding and explaining hereditary predisposition to cancer has focused on the genetic etiology of the disease. However, mutations in known genes associated with breast cancer such as BRCA1 and BRCA2 account for less than 25% of familial cases of breast cancer. Heritable epigenetic modifications, in the form of hypermethylated MLH1 promoter alleles, have recently been shown to promote hereditary nonpolyposis colorectal cancer. We investigated the potential for an epigenetic basis for hereditary breast cancer by performing deep bisulfite sequencing of CpG islands and known promoter regions in germline DNA from 100 familial or early-onset breast or ovarian cancer patients.

  Study phs001699

• FinaleMe: Predicting DNA Methylation by the Fragmentation Patterns of Plasma Cell-Free DNA

  Analysis of DNA methylation in cell-free DNA (cfDNA) reveals clinically relevant biomarkers but requires specialized protocols and sufficient input material that limits its applicability. Millions of cfDNA samples have been profiled by genomic sequencing. To maximize the gene regulation information from existing datasets, we developed FinaleMe, a non-homogeneous Hidden Markov Model (HMM), to predict DNA methylation of cfDNA and, therefore, tissues of origin directly from plasma whole genome sequencing (WGS). We validated the performance with 80 pairs of deep and shallow coverage WGS and whole genome bisulfite sequencing (WGBS) data from both cancer patients and healthy controls.

  Study phs003287

• EWS-WT1 Fusion Isoforms Establish Oncogenic Programs and Therapeutic Vulnerabilities in Desmoplastic Small Round Cell Tumors

  Desmoplastic Small Round Cell Tumor (DSRCT) is an aggressive mesenchymal tumor driven by fusions between the disordered domain of the Ewing sarcoma RNA binding protein 1 (EWSR1) and the developmental transcription factor Wilms tumor 1 (WT1). We used genome-wide chromatin profiling to identify EWSR1-WT1-dependent gene regulatory networks and target genes. Our studies show that EWS-WT1 is a powerful activator of distal regulatory elements and controls an oncogenic gene expression program that characterizes primary DSRCTs. ChIP-seq profiles for histone marks in primary DSRCT samples are available through dbGaP.

  Study phs003682

• ScRNA-seq of human kidney immune cells of patients with ANCA-associated glomerulonephritis, Lupus Nephritis against a healthy nephrectomy control

  ANCA-associated glomerulonephritis (AGN) associates with a high risk of end-stage kidneydisease. The role of kidney immune cells in local inflammation remains unclear. This study investigates kidney immune cell diversity and function. Kidney tissue from AGN patients (n=5) and a lupus nephritis (LN) patient (n=1) were aquired during a biopsy procedure for a clinical indication. Needle-core biopsies were obtained for histopathological examination, and an additional pass was performed to retrieve kidney tissue for scRNA-seq. Healthy kidney tissue (n=1) was obtained from a kidney that was surgically removed do tue due to a (non-invasive) papillary urothelial carcinoma. Immediately after collection, kidney tissue was processed into a single-cell suspension and sorted using a 4-color flow cytometry panel to isolate living, CD45+immune cells. To aid in the multi-omic characterization, surface markers and T and B cell repertoires were sequenced in 2 samples (1 AGN patient and the nephrectomy control). These samples were incubated with an oligo-antibody TotalSeq-C cocktail containing 130 unique cell surface antigens.

  Dataset EGAD50000000229

• A genome-wide CRISPR screen identifies CALCOCO2 as a regulator of beta cell function influencing type 2 diabetes risk

  Identification of the genes and processes mediating genetic association signals for complex diseases represents a major challenge. As many of the genetic signals for type 2 diabetes (T2D) exert their effects through pancreatic islet-cell dysfunction, we performed a genome-wide pooled CRISPR loss-of-function screen in a human pancreatic beta cell line. We assessed the regulation of insulin content as a disease-relevant readout of beta cell function and identified 580 genes influencing this phenotype. Integration with genetic and genomic data provided experimental support for 20 candidate T2D effector transcripts including the autophagy receptor CALCOCO2. Loss of CALCOCO2 was associated with distorted mitochondria, less proinsulin-containing immature granules and accumulation of autophagosomes upon inhibition of late-stage autophagy. Carriers of T2D-associated variants at the CALCOCO2 locus further displayed altered insulin secretion. Our study highlights how cellular screens can augment existing multi-omic efforts to support mechanistic understanding and provide evidence for causal effects at genome-wide association studies loci.

  Dataset EGAD50000000518

• "BaTwa" populations from Zambia retain ancestry of past hunter-gatherer groups

  We genotyped and analyzed over two million genome-wide SNPs from two BaTwa populations (40 individuals by population), and from three comparative farming populations (10 to 21 individuals by population) in order to: (i) determine if the Zambian BaTwa carry any genetic material linking them to past hunter-gatherer-groups, and (ii) characterize the genetic affinities of past Zambian hunter-gatherer-groups. We found that both BaTwa populations harbor a hunter-gatherer- like genetic component, representing ∼19% (Bangweulu) and ∼31% (Kafue) of their genetic ancestry, while the rest of their ancestry is similar to western Africans.

  Study EGAS50000000378

• Ancient genomes reveal insights into ritual life at Chichén Itzá

  To better understand the origin and biological relationships of the sacrificed children from Chichén Itzá to each other and to present-day inhabitants of the region, here we used a combined bioarchaeological and genomics approach to investigate 64 subadults interred within a chultún near the Sacred Cenote and compare them to 68 present-day Maya inhabitants of the nearby town of Tixcacaltuyub, as well as to other available ancient and contemporary genetic data from the region. The community of Tixcacaltuyub has been collaborating with our research team for many years, and their perspectives informed the development of this project.

  Study EGAS50000000296

• Proteomic predictors of individualized nutrient-specific insulin secretion in health and disease

  Population level variation and molecular mechanisms behind insulin secretion in response to carbohydrate, protein, and fat remain uncharacterized despite ramifications for personalized nutrition. We now define prototypical insulin secretion dynamics in response to the three macronutrients in islets from 140 cadaveric donors, including those diagnosed with type 2 diabetes. We leverage the insulin response heterogeneity and use transcriptomics and proteomics to identify molecular pathways of specific nutrient responsiveness. Surprisingly, we find robust insulin secretion to fatty acid stimulus in ~8% of donors, challenging the idea that fat has negligible effects on insulin release. Distinct islet proteomes with differences in metabolic signalling networks convey this hyper-responsiveness to fat relative to carbohydrate. By comparing human islets to human embryonic stem cell-derived islet clusters, we show that, unlike glucose-responsiveness, fat hyper-responsiveness is equivalent and may be a hallmark of functionally immature cells. Our study represents the first comparison of dynamic responses to nutrients and multi-omics analysis in human insulin secreting cells. Responses of different people’s islets to carbohydrate, protein, and fat lay the groundwork for personalized nutrition.

  Dataset EGAD50000000519

• Immune signature of malignant melanoma in pregnancy

  Melanoma is a highly immunogenic malignancy and there is a deep-rooted notion among clinicians that a probable systemic immunosuppressed state during pregnancy would negatively influence melanoma related prognosis. To test this hypothesis on a more fundamental level, we collected a unique set of melanoma tumor samples and performed RNAseq to draw comparisons between the immune cell infiltrate of pregnant patients and non-pregnant matched controls. We found that there is indeed no differential expression of any immune cell subset. This underscores the notion that the supposed immunosuppressive state of pregnancy does not hamper the anti-tumor immune response.

  Study EGAS50000000492

• Spatiotemporal single-cell roadmap of human skin wound healing

  Wound healing is vital for human health, yet the details of cellular dynamics and coordination in human wound repair remain largely unexplored. To address this, we conducted single-cell and spatial transcriptomics analyses on human skin and acute wound tissues through inflammation, proliferation, and remodeling phases of wound repair from the same individuals, monitoring the cellular and molecular dynamics of human skin wound healing at an unprecedented spatiotemporal resolution. Comparison with single-cell data from venous and diabetic foot ulcers uncovers a link between failed keratinocyte migration and impaired inflammatory response in chronic wounds.

  Study EGAS50000000571

• Gabriella Miller Kids First Pediatric Research Program in Bladder Exstrophy, Epispadias, Complex (BEEC)

  Urogenital anomalies account for 20-30% of prenatally detected structural defects. Bladder Exstrophy Epispadias Complex (BEEC) describes a subset of anomalies with a spectrum of developmental defects ranging from a mild form of epispadias, to classic bladder exstrophy, to omphalocele, exstrophy, imperforate anus, spinal anomalies (OEIS) complex. Patients with BEEC suffer substantial morbidity and mortality due to impaired genito-urinary dysfunction. The etiology of BEEC is largely unknown. Elucidating the underlying genetic component is critical to gaining a better understanding of the developmental signaling pathways and is likely the first step to developing targeted therapy.

  Study phs002173

• Epigenomics of Prostate Cancer from Cell Free Plasma

  We sought to perform epigenomic characterization of prostate cancers by profiling circulating nucleosomes isolated from patient plasma using cell free chromatin immunoprecipitation followed by sequencing (cfChIP-seq). Our major findings include identification of prostate-cancer specific regulatory elements using a novel statistical method accounting for variable tumor DNA fraction in plasma, inferring transcription factor activity based on binding motif enrichment within regulatory elements, and epigenetically phenotyping patients based on clinical and genomic features. Data available in dbGaP will include cfChIP-seq and targeted sequencing from approximately 50 patients with a known diagnosis of cancer and healthy patient controls.

  Study phs003482

• Divergent WNT Signaling and Drug Sensitivity Profiles within Hepatoblastoma Tumors and Organoids

  Hepatoblastoma, the most prevalent pediatric liver cancer, almost always carries a WNT-activating CTNNB1 mutation, yet exhibits notable molecular heterogeneity. To characterize this heterogeneity and identify novel targeted therapies, we perform comprehensive analysis of hepatoblastomas and tumor-derived organoids using single-cell RNA-seq/ATAC-seq, spatial transcriptomics, and high-throughput drug profiling. We identify two distinct tumor epithelial signatures: hepatic ‘fetal’ and WNT-high ‘embryonal’, displaying divergent WNT signaling patterns. The fetal group is enriched for liver-specific WNT targets, while the embryonal group is enriched in canonical WNT target genes.

  Study EGAS50000000561

• RNA-seq of longitudinal human blood and nose swab samples from a controlled human infection experiment with SARS-CoV-2 virus

  Controlled human infection experiments enable longitudinal profiling of immune responses to a pathogen. 36 healthy volunteers aged 18-29 years, with no evidence of previous infection or vaccination, were inoculated with SARS-CoV-2 virus and quarantined for 14 days. Blood samples for RNA sequencing were collected into PAXgene tubes before virus challenge, 6 hours after challenge, daily thereafter for 14 days and on day 28. Mid-turbinate nose swabs for RNA sequencing were collected before virus challenge, and on days 1, 3, 5, 7, 10 and 14 after challenge, preserved in RNAprotect.

  Study EGAS50000000667

• High-resolution profile of neoantigen-specific TCR activation links moderate stimulation to increased resilience of engineered TCR-T cells

  Neoantigen-specific T cell receptors (neoTCRs) promise safe, personalized anti-tumor immunotherapy. Previously, we identified diverse neoTCRs restricted to different neoantigens in a melanoma patient. In this work, we now combined single-cell TCR- and RNA-sequencing after neoantigen-specific restimulation of peripheral blood-derived CD8+ T cells of this patient. We detected novel neoTCRs with specificity to the previously detected neoantigens and observe a heterogeneous spectrum of TCR-intrinsic activation patterns in response to a shared neoepitope ranging from previously detected higher frequent neoTCRs with moderate activation to rare ones with initially stronger activation.

  Study EGAS50000000600

• Oncogene activated human breast luminal progenitors contribute basally located myoepithelial cells

  Basal-like breast cancer originates in luminal progenitors, frequently with an altered PI3K pathway, and focally in close association with genetically altered myoepithelial cells at the site of tumor initiation. The exact trajectory behind this bi-lineage phenomenon remains poorly understood. Here we used a breast cancer relevant transduction protocol including hTERT, shp16, shp53, and PIK3CA(H1047R) to immortalize FACS isolated luminal cells, and we identified a candidate multipotent progenitor. We found that the apparent luminal phenotype of these oncogene transduced progenitors was metastable giving rise to basal-like cells dependent on culture conditions.

  Study EGAS50000000505

• Addiction of Primary Cutaneous Gamma-Delta T-cell Lymphomas to JAK-STAT Signaling

  Primary cutaneous γδ T-cell lymphoma (PCGDTL) is a mature T-cell lymphoma (TCL) of the skin with a median survival of 31 months and no effective therapies. PCGDTLs frequently possess mutations in the JAK/STAT pathway, including in JAK1, JAK3, STAT3, STAT5B, and SOCS1. We hypothesized that single-agent JAK inhibition may be effective in PCGDTLs, particularly those with targetable JAK/STAT pathway mutations. Herein, we demonstrate the near-complete response of two PCGDTL cases to single-agent JAK inhibitors, ruxolitinib or cerdulatinib. However, both patients eventually relapsed with acquired mutations in JAK1, JAK3, or STAT5B.

  Study phs003837

• Integrated Transcriptomic and Regulatory RNA Profiling Reflects Complex Pathophysiology and Uncovers a Conserved Gene Signature in End Stage Heart Failure RNA-Seq data

  Heart failure (HF) is a complex syndrome. Despite availability of multiple treatment options, the mortality remains high and the quality of life poor. Better understanding of the underlying pathophysiological processes can lead to development of novel therapies. Multiple comparative transcriptomics studies, which revealed gene level changes in the key pathophysiological pathways in failing hearts, point towards heterogeneity from interplay of disease stage, etiologies and ethnicity. Transcriptomic characterization of HF in patients from different ethnicities can potentially help in understanding the heterogeneity imparted by various factors and the core elements in heart failure.

  Study EGAS50000000810

• Enabling sensitive and precise detection of ctDNA through somatic copy number aberrations in breast cancer

  Cell-free DNA (cfDNA) extracted from peripheral blood has emerged as a crucial biomarker source in oncology research. To enhance the detection of somatic copy number alterations (SCNAs) and circulating tumor DNA (ctDNA), we developed eSENSES, a 2Mb breast cancer-targeted NGS panel. It includes 15,000 genome-wide SNPs, 500 focal SNPs in breast cancer driver regions, and exons from 81 commonly altered genes, alongside a custom computational approach. eSENSES provides a reliable, powerful and cost-effective tool for monitoring disease progression and guiding therapeutic decisions in breast cancer patients.

  Study EGAS50000000793

• Comparison of transcriptomics profile of stem cell-derived beta cells from HUES8 and RC9

  Stem cell-derived islet cells have a potential to be used to restore endogenous insulin production in people with diabetes. The goal of this experiment is to compare the transcriptomics profile of stem-cell derived beta cells from two different cell lines: HUES8 (non-clinical grade) and RC9 (clinical grade) in terms of beta cell identity and maturity. Stem cell-derived islets were produced using differentiation protocol detailed in Rajaei et al. 2025 (manuscript approved in Science Translational Medicine, pending pubmed ID). Single cell transcriptomics data were generated using 10x Genomics 3' Single Cell Gene Expression kit.

  Study EGAS50000000905

• INfluenza Vaccine to Effectively Stop Cardio Thoracic Events and Decompensated Heart Failure (INVESTED)

  INVESTED was planned as a large, adequately powered, multicenter trial to assess the cardiopulmonary benefit of high- compared with standard-dose influenza vaccine in a high-risk cardiovascular population. In contrast to more complex interventions in patients with cardiac disease, the major potential benefits of this intervention are a) the ease of administration, b) low cost, c) 100% vaccination adherence and d) well established and extremely low risk. This trial, if positive, has the potential to substantially impact a major population attributable CV risk, change practice, and inform health policy by boosting utilization of influenza vaccination.

  Study phs004011

• Changes in AXL and/or MITF melanoma subpopulations in patients receiving immunotherapy

  Our data demonstrate large interpatient variability and variable therapy-induced changes independent of the type of therapy. We identify the presence of previously described AXL+ and MITF+ subpopulations in metastatic tissues both at the mRNA level and in situ at the protein level, and demonstrate that MITF+ melanoma cells are significantly decreased upon immunotherapy, while AXL+ melanoma cell numbers are stable. MITF+ tumor cells showed the most significant inverse correlation with CD8+ T cells. Our patient cohort also shows that immunotherapy-induced changes in the abundance of AXL+ or MITF+ tumor cells did not correlate with improved survival.

  Study EGAS50000001080

• Single cell transcriptomics of human kidney organoid endothelium reveals vessel growth processes and arterial maturation upon transplantation

  Human induced pluripotent stem cell-derived kidney organoids have potential for disease modeling and regenerative medicine purposes. However, they lack a functional vasculature in in vitro culture. Here, we transplanted kidney organoids at day 7+12 of differentiation in the coelomic cavity of chicken embryos. We then compared human endothelial cells from transplanted organoids to their respective untransplanted controls at d7+13 and d7+20 using scRNAseq. We demonstrate metabolic and phenotypic effect of transplantation with increased endothelial cell proliferation and differentiation to a fetal-like renal arterial/afferent arteriolar phenotype.

  Study EGAS50000001068

• ERBB2/HER2 alterations in ctDNA and metachronous tissues of patients with metastatic urothelial cancer - WGS

  Whole genome sequencing data related to the publication "ERBB2/HER2 alterations in ctDNA and metachronous tissues of patients with metastatic urothelial cancer." ERBB2 alterations, usually amplifications or activating mutations, are seen in up to 20% of urothelial carcinoma and can be targeted by monoclonal antibodies, small molecule inhibitors, and most recently, antibody-drug conjugates. Here, we perform targeted and whole-genome sequencing of cell-free DNA and archival FFPE of mUC with and without ERBB2 alterations to identify unique genomic and clinical features of ERBB2-altered cancers, accompanied by IHC, FISH, and detailed clinical outcomes.

  Study EGAS50000001082

• ERBB2/HER2 alterations in ctDNA and metachronous tissues of patients with metastatic urothelial cancer - Targeted

  Targeted sequencing data related to the publication titled "ERBB2/HER2 alterations in ctDNA and metachronous tissues of patients with metastatic urothelial cancer." ERBB2 alterations, usually amplifications or activating mutations, are seen in up to 20% of urothelial carcinoma and can be targeted by monoclonal antibodies, small molecule inhibitors, and most recently, antibody-drug conjugates. Here, we perform targeted and whole-genome sequencing of cell-free DNA and archival FFPE of mUC with and without ERBB2 alterations to identify unique genomic and clinical features of ERBB2-altered cancers, accompanied by IHC, FISH, and detailed clinical outcomes.

  Study EGAS50000001081

• Systematic Analysis of Transcription Program Regulation by Transcription Factor EB (TFEB)

  In order to evaluate the effects of TFEB, a master regulator of autophagy and lysosomal biogenesis, CRISPR-Cas9 TFEB knock out cell lines were generated and reconstituted with wild-type TFEB (TFEB-WT), a vector control (TFEB-KO) or TFEB engineered to remain localized to the cytosol (TFEB-cyto) or to the nucleus (TFEB-nuc). RNA sequencing was performed on engineered cell lines at steady-state or following exogenous stimulation with autophagy inducer (Torin1 or Salmonella bacterial infection). Comparative analyses were performed to identify TFEB-dependent transcriptional response to subcellular localization at steady-state or to exogenous stimuli.

  Study phs002099

• ATACseq - Notch Signaling Maintains a Progenitor-Like Subclass of Hepatocellular Carcinoma

  To assess how Notch inhibition impacts chromatin accessibility and how chromatin changes relate to HNF4A and CEBPA activities, we performed Assay-for-Transposase-Accessible-Chromatin (ATAC) sequencing of LIV78 tumors, 72 hours after treatment with NOTCH2 blocking or control antibodies. Our TF activity and chromatin analyses thus lead to a model in which Notch inhibition leads to increased expression of CEBPA, thus enabling CEBPA to partner with HNF4A to jointly drive transcriptional programs and the underlying chromatin rearrangements that promote differentiation of progenitor-like tumor cells to a mature hepatocyte fate incompatible with tumor growth and maintenance.

  Study EGAS50000000516

• ABHD11 inhibition drives sterol metabolism to modulate T cell effector function and alleviate autoimmunity

  Chronic inflammation in autoimmunity is driven by hyperactive T cells with dysregulated metabolism. ABHD11 is a mitochondrial hydrolase that supports alpha-ketoglutarate dehydrogenase function and has been associated with remission in rheumatoid arthritis. To explore its role in T cell function, we used CRISPR/Cas9 to knock down ABHD11 in Jurkat T cells and performed RNA-Seq analysis. Differential gene expression revealed widespread transcriptional changes, with sterol-related pathways among the most significantly enriched. These findings highlight ABHD11 as a potential regulator of metabolic programming in T cells with implications for autoimmunity.

  Study EGAS50000001297

• A non-canonical lymphoblast in refractory childhood T-cell leukaemia

  Refractory cancers may arise either through the acquisition of resistance mechanisms by cancer cells or represent distinct diseases. The origin of childhood T-cell acute lymphoblastic leukaemia (T-ALL) that does not respond to initial treatment, i.e. refractory disease, is unknown. Refractory T-ALL carries a poor prognosis and cannot be predicted at diagnosis. Here, we performed single cell mRNA sequencing of T-ALL from children who did or did not respond to initial treatment. We identified a transcriptionally distinctive blast population, exhibiting features of innate-like lymphocytes, as the major source of refractory disease.

  Study EGAS50000000767

• Development of Novel Synovial Sarcoma Organoids Models for Drug Discovery

  Although synovial sarcoma has been studied using established cell lines and mouse models, effective treatments remain limited. We treated five patients with synovial sarcoma between 2022 and 2023 and established organoid cultures from resected tumor specimens using a modified air-liquid interface method. After serial passaging, organoids were successfully xenografted into NOD-scid IL2Rgnull (NSG) mice in three cases. The established organoids retained SS18-SSX fusion transcripts and demonstrated histological and genetic similarities to the original tumors. These organoid models provide a reliable platform for studying synovial sarcoma biology and hold promise for the development of novel therapeutic strategies.

  Study JGAS000806

• WES analysis of paired tumor and non-tumoral DNA of 4 patients with non-muscle-invasive bladder cancer

  We performed WES of tumor DNA and non-tumoral DNA (extracted from PBMC) of 4 patients with non-muscle invasive bladder cancer, who after the tumor resection went on to receive BCG treatment as they had high-risk disease. In order to identify tumor-specific mutations that could give rise to patient-specific neo-epitopes, we performed paired WES of tumor and non-tumoral DNA for each patient. For patient UC2, 3 different tumors were resected at the same time and DNA from these 3 tumors were sent separately for WES.

  Study EGAS50000001382

• Global Architecture of anti-Tumor B-Cell Immunity against Gastric Cancer

  Recent successes in tumor immunotherapies have warranted the importance of tumor immunity. Compared to the T-cell immunity, B-cell immune system in cancer is largely elusive. Here we immunogenetically profiled tumor-infiltrating B-cell and T-cell repertoires for exome- characterized diffuse-type gastric carcinoma (DGC), which is remarkable for its B-cell infiltrations, unraveling previously un-defined architectures of B-cell immunity and its interplays with T-cell immunity in cancer. We also performed transcriptome analysis to enumerate the proportions of tumor-infiltrating immune cells in the gastric cancer environment .

  Study JGAS000141

• CAGE analysis for endometrial carcinoma

  For endometrial cancer patients, lymphadenectomy is recommended to exclude rarely metastasized cancer cells. This procedure is performed even in patients with low risk of recurrence despite the risk of complications such as lymphedema. A method to accurately identify cases with no lymph node metastases (LN-) before lymphadenectomy is therefore highly required. We approached this clinical problem by examining primary lesions of endometrial cancers with CAGE (Cap Analysis Gene Expression), which quantifies promoter-level expression across the genome. Fourteen profiles delineated distinct transcriptional networks between LN?+?and LN- cases, within those classified as having the low or intermediate risk of recurrence.

  Study JGAS000124

• Expression quantitative trait loci analysis using human immune cells in a Japanese population

  Recent evidence suggests that a substantial portion of complex disease risk alleles modify gene expression in a cell-specific manner. Therefore, it is reasonable to expect that cell-specific expression quantitative trait loci (eQTL) analysis can identify the candidate causal mechanisms of complex diseases (an eQTL is a variant whose polymorphism affects gene expression). We fractionated peripheral blood from 105 healthy Japanese volunteers into five major immune cell subsets (CD4+ T cells, CD8+ T cells, B cells, NK cells, and monocytes). We quantified gene and exon expression by RNA sequencing, and tested associations with neighboring common variants (MAF ? 0.05).

  Study JGAS000085

• Global Architecture of anti-Tumor B-Cell Immunity against Gastric Cancer

  Recent successes in tumor immunotherapies have warranted the importance of tumor immunity. Compared to the T-cell immunity, B-cell immune system in cancer is largely elusive. Here we immunogenetically profiled tumor-infiltrating B-cell and T-cell repertoires for exome- characterized diffuse-type gastric carcinoma (DGC), which is remarkable for its B-cell infiltrations, unraveling previously un-defined architectures of B-cell immunity and its interplays with T-cell immunity in cancer. We also performed transcriptome analysis to enumerate the proportions of tumor-infiltrating immune cells in the gastric cancer environment .

  Study JGAS000103

• Whole exome sequencing of uterine adenomyosis

  Uterine adenomyosis, defined by proliferation of the ectopic endometrial glands in myometrium, is a common benign uterine disorder that significantly impairs the quality of life of the women it affects. Adenomyosis lesions have chronic inflammatory reactions as well as cancer-like features such as invasive capacity into the normal myometrium. In contrast to endometriosis and leiomyoma, the genomic characterization of adenomyosis has yet to be reported. We conducted high-coverage whole exome sequencing analyses of freshly frozen adenomyosis samples, as well as co-occurring leiomyoma. Our WES analyses showed that adenomyosis is a clonal disorder with somatic mutations.

  Study JGAS000169

• Reconstruction of the personal information from human genome reads in gut metagenome sequencing data

  Human DNA present in fecal samples can result in a small number of human reads in gut shotgun metagenomic sequencing data. However, it is currently unclear how much personal information can be reconstructed from such reads and this has not been quantitatively evaluated. Such a quantitative evaluation is necessary to clarify the ethical concerns related to data sharing and to enable the efficient use of human genetic information in stool samples, such as for research and forensics. Here, we used genomic approaches to reconstruct personal information from fecal metagenomes of 343 Japanese individuals with associated human genotype data.

  Study JGAS000600

• RNA expression profiling of neuromuscular diseases and viral diseases

  MicroRNAs (miRNAs), particularly those found in human body fluids, have been suggested as potential biomarkers. Among various body fluids, the cerebrospinal fluid (CSF) shows promise as a profiling target for diagnosis and monitoring of neurological diseases. However, relevant genome-scale studies are limited and no studies have profiled exosomal miRNAs in CSF. Therefore, we conducted a next-generation sequencing-based survey of small RNAs in the exosomal and non-exosomal (supernatant) fractions of healthy human CSF as well as serum in each donor. Our data provided the first landscape of small RNAs in CSF exosome.

  Study JGAS000064

• Japanese Reference Genome JG1

  The complete human genome sequence is used as a reference for next-generation sequencing analyses. However, some ethnic ancestries are under-represented in the reference genome (e.g., GRCh37) due to its bias toward European and African ancestries. Here, we perform de novo assembly of three Japanese male genomes using >100�� Pacific Biosciences long reads and Bionano Genomics optical maps per sample. We integrate the genomes using the major allele for consensus and anchor the scaffolds using genetic and radiation hybrid maps to reconstruct each chromosome. The resulting genome sequence, JG1, is contiguous, accurate, and carries the major allele for a Japanese population.

  Study JGAS000259

• Germline pathogenic variant and gastric cancer risk

  Germline pathogenic variants in some genes have been suggested to be associated with gastric cancer risk, although large-scale evaluations were limited. Herein, we analyzed germline variants in 27 cancer-predisposing genes in 10,426 gastric cancer patients and 38,153 controls from BioBank Japan. Following quality control of sequencing data, samples from 10,366 gastric cancer patients and 37,592 controls were further analyzed. We evaluated the association between pathogenic variants and gastric cancer risk and explored the characteristics of the pathogenic-variant carrier. Nine genes were associated with gastric cancer risk. The germline pathogenic variant carriers showed different clinical and demographic characteristics.

  Study JGAS000592

• Integrative understanding of human immune system by functional genomics and development of intervention strategies for the prevention of autoimmune diseases

  To elucidate the regulation of B cell recptor repertoire in B cell subsets and its contribution to autoimmune diseases, B cell subsets from 36 Systemic Lupus Erythematosus(SLE), 90 Systemic Sclerosis(SSc), 85 Myositis(IIM), 21 Mixed Connective Tissue Disease(MCTD), 18 Sjogren's syndrome(SjS), 27 Rheumatoid Arthritis(RA), 23 Behcet's disease(BD), 18 Adult Onset Still���s Disease(AOSD), 24 ANCA-associated Vasculitis(AAV), 16 Takayasu���s Arteritis(TAK) and 137 healthy controls(HC) were collected (Naive_B, USM_B, SM_B, DN_B, Plasmablast. RNA-seq and BCR-mapping was performed with each B cell subset samples.

  Study JGAS000485

• Adult B-precursor acute lymphoblastic leukemia RoCK and ROI single-cell transcriptome

  Whohle Transcriptome sequencing was performed following the manufactures protocol from BD Rhapsody. Capture of BCR::ABL1 was performed using RoCK and ROI. RoCK and ROI is based on barcoded beads of the BD Rhapsody platform. For RoCKseq specific capture, TSO oligos on BD Rhapsody beads are modified with a/ multiple capture sequence(s) specific to transcripts of interest. ROIseq, on the other hand, is based on specific primers which are spiked in during library generation, directing reads to regions of interest (ROIs). Multiple scRNAseq experiments were performed on several biological samples to validate RoCK and ROI.

  Study EGAS50000001366

• Whole genome sequencing data of paediatric KMT2A-rearranged acute lymphoblastic leukemia

  Pediatric KMT2A-rearranged leukemia is an aggressive subtype of leukemia commonly seen in infants (less tha 1 year old) and young children. It involves rearrangements of the KMT2A gene (formerly MLL) on chromosome 11q23, resulting in fusion genes that drive uncontrolled cell growth. This subtype is most often found in acute lymphoblastic leukemia (ALL) and acute myeloid leukemia (AML) and is associated with a poor prognosis. In infants, the 5-year event-free and overall survival rates are around 35–40%. Despite intensive chemotherapy, outcomes remain challenging, prompting ongoing research into targeted therapies and novel treatment strategies.

  Study EGAS50000001079

• B cell activation

  To investigate the gene programs involved in B cell activation and antibody switching, we profiled the gene expression at the single cell level as well as the antibody repertoire of human naive and memory B cells at resting and following three time points of activation. Through CRISPR perturbations, we defined IRF4 as a central regulator of both GC and plasma cell fates, acting independently of PRDM1 in GC commitment. Finally, leveraging machine learning classification methods trained solely on transcriptomic profiles, we accurately predicted sister cell relationships, revealing that plasma cell gene expression programs are heritable and tightly conserved within a clone.

  Study EGAS50000001468

• Drug Perturbation of Primary Lymphoma Patient Samples and RNA Sequencing

  This submission contains 3'-end-based shallow-depth RNA sequencing data from 108 patients with chronic lymphocytic leukemia and 8 patients with lymphoma. Each primary patient sample was treated in vitro with DMSO as a control and with up to ten small-molecule drugs (ibrutinib, duvelisib, everolimus, trametinib, nutlin-3a, I-BET762, MK2206, selinexor, compound 26, and a combination of ibrutinib and compound 26). The samples were sequenced after 48 hours. The total data set consists of 1476 RNA sequencing samples from 6 batches (pilot, batch 1, batch 1 replicate, batch 2, batch 3, batch 4).

  Study EGAS50000001500

• PD-associated regulatory variants in human dopaminergic neurons reveals modulators of SCARB2 and BAG3 expression

  SNPs have been associated with the risk of Parkinson’s disease but not in regulatory regions. While those potentially disrupt TFBS altering gene expression and contributing to cis-regulatory variation. To study changes in A and B compartment interactions and in topologically associated domains (TADs), we sequenced: - 3D chromatin contact using LowC, 6 samples. 3 replicates for each condition: smNPC (controls) cells and differentiated neurons after 30 days. Resulting paired-end are provided as BAM files. In order to confirm the predicted impact of the PD-associated allele of rs144814361 on BAG3 promoter, we proceeded with genome editing of the TH-REP1 cell line by using prime editing to insert the “T” allele at the position chr10:119651405 in the BAG3 promoter. - Chromatin accessibility using ATAC-seq, 9 samples of derived cell line TH-REP1. 3 replicates for each condition: 1) iPSC Wild Type 2) SNP-BAG3 variant in iPSC 3) SNP-BAG3 variant in smNPC. BAG3 variant: heterozygous for the SNP variant: rs144814361 (chr10 119651405) Resulting sequencing are provided as paired-end FASTQ files.

  Dataset EGAD50000002258

• Discordant_Monozygotic_Twins_ALS(Transcriptomics)

  Amyotrophic lateral sclerosis (ALS) is a progressive neurodegenerative disorder characterized by motor neuron degeneration. Despite known genetic contributions to both familial and sporadic ALS cases, much of ALS heritability remains unexplained, suggesting the involvement of other genetic and epigenetic factors. To address this gap, we used a comprehensive multi-omics approach, in a pair of Italian monozygotic twins discordant for ALS, integrating DNA methylation, transcriptomics, and whole exome sequencing (WES). Here we share transcriptomic data derived from bulk RNA-seq on RNA extracted from PBMCs of the twin pair. This analysis revealed distinct transcriptomic profiles underlying the discordant disease phenotypes.

  Study EGAS50000000909

• Spatial predictors of response to immunotherapy in microsatellite stable metastatic colorectal cancer

  Microsatellite stable (MSS) colorectal cancers (CRC) are largely unresponsive to immune checkpoint inhibition (ICI), prompting investigation into strategies to enhance sensitivity. The MAYA trial, which utilized temozolomide (TMZ) in MGMT-silenced MSS mCRC, hypothesized that TMZ-induced hypermutation could sensitize tumors to ICI. This phase II trial met its primary endpoint, demonstrating durable clinical responses with TMZ combined with ipilimumab and nivolumab. To elucidate factors in uencing response heterogeneity, we conducted multi-omic spatial pro ling of samples from patients who participated in the MAYA trial, including baseline and on-treatment tissue and blood specimens. While increased neoantigen load following TMZ exposure did not consistently predict for deep responses, spatial profiling revealed key determinants. Lymphocyte proportions, particularly CD8+KI67+ cells, within stromal and tumor compartments, along with macrophage composition (CD68+CD163+ cells) at the tumor-stromal interface, were predictive of response. Treatment pressures dynamically altered the tumor microenvironment composition and activated peripheral immune cells. This study is the first to identify spatial predictors of response to this promising novel treatment approach for MSS CRC.

  Dataset EGAD50000002244

• Identification_of_drug_resistance_genes_in_cancer_cell_lines_by_insertional_mutagenesis

  Our aim is to identify genes involved in resistance to anti-cancer therapies. In order to do this we have taken advantage of a lentiviral vector (LV)-based insertional mutagen to mutagenize cancer cell lines. LV-transduced cell lines were then treated with anti-cancer therapies and the emergence of resistant clones scored. DNA from pools of resistant clones was collected, subjected to custom capture by baits designed against the LV sequence, and then sequenced to identify the LV-genomic junction. We hope that the identification of recurrently targeted genes in resistant cell population will allow us to identify genes that mediate drug resistance.

  Study EGAS00001001035

• Breast Cancer - Very young women

  This project will focus on sequencing of breast cancer from young age cancer patients characterized by age at diagnosis under 35. Based on the incidence rate by Korean National Cancer Incidence Database, breast cancer is the most common solid tumors among young adults aged 15-34 excepting thyroid cancer (Cancer statistics in Korea (2012)). This project just started from the mid of 2015. National cancer center in Korea are collecting more than 100 tumor specimens from breast cancer patients aged 20-34. Genetic features of young patients will be investigated with somatic mutation pattern, structural variations, and canonical pathways.

  Study EGAS00001001908