7188 results for "({!join from=dataset_studies to=id v=$q1}) OR ("transcriptome" OR "RNA-seq" OR "rna sequencing" OR "rna-sequencing")"

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• Yale SPORE in Skin Cancer Project 2

  Understanding the relationship between tumor and peripheral immune environments could allow longitudinal immune monitoring in cancer. Here, we examined whether T cells that share the same TCRab and are found in both tumor and blood can be interrogated to gain insight into the ongoing tumor T cell response. Paired transcriptome and TCRab repertoire of circulating and tumor-infiltrating T cells were analyzed at the single cell level from matched tumor and blood from patients with metastatic melanoma. The data shared here consist of gene expression matrix and fastq files obtained from sequencing single-cell libraries generated with the Chromium (TM) 5' technique. For each of 18 immunotherapy naive and 11 previously treated melanoma patients, T cells (Live/CD45+/TcRab+) were FACS-sorted from PBMCs and freshly resected tumors. Metadata associated with each individual cell consist of Patient I.D., biological sex, immunotherapy status, amino acid and nucleotide CDR3 sequence of the TCR alpha and beta chain (obtained from matched VDJ region enriched libraries), and sequencing batch. Further details about previous treatment history and other clinical parameters can be found in the associated manuscripts (Lucca et al., 2021: PMID: 33651881; Lu et al., PMID: 39609626).

  Study phs002289

• Atezolizumab Plus Chemotherapy With or Without Bevacizumab in Advanced Biliary Tract Cancer: Clinical and Biomarker Data From the Randomized Phase II IMbrave151 Trial

  PURPOSE Biliary tract cancers (BTCs) harbor an immunosuppressed tumor microenvironment (TME) and respond poorly to PD-1/PD-L1 inhibitors. Bevacizumab (anti-VEGF) plus chemotherapy can promote anticancer immunity, augmenting response to PD-L1 inhibition. PATIENTS AND METHODS This randomized, double-blind, proof-of-concept Phase II study enrolled patients (n=162) with previously untreated advanced BTC (IMbrave151; NCT04677504). Patients were randomized 1:1 to receive 3-weekly cycles of atezolizumab (1200 mg) plus bevacizumab (15 mg/kg) or atezolizumab plus placebo until disease progression or unacceptable toxicity. All patients received cisplatin (25 mg/m2) plus gemcitabine (1000 mg/m2; CisGem) on Days 1 and 8 every 3 weeks for up to 8 cycles. Stratification of patients was by disease status, geographic region, and primary tumor location. The primary endpoint was progression-free survival (PFS). No formal hypothesis testing was performed. Exploratory correlative biomarker analysis was undertaken using transcriptome analysis (n=95) and mutation profiling (n=102) on baseline tumor samples. RESULTS Between February and September 2021, 162 patients were enrolled. Median PFS was 8.3 months in the bevacizumab arm and 7.9 months in the placebo

  Study EGAS50000000387

• The genomic basis of childhood T-lineage acute lymphoblastic leukemia

  T-lineage acute lymphoblastic leukemia (T-ALL) is a high-risk tumor that has eluded comprehensive genomic characterization, in part due to the high frequency of non-coding genomic alterations resulting in oncogenic dysregulation. Here we report integrated genome and transcriptome sequencing of T-ALL tumor and remission samples obtained from over 1300 uniformly treated children with T-ALL, coupled with epigenomic and single cell analysis of malignant and normal T cell precursors. Integrated analysis identified 15 subtypes with distinct genomic drivers, gene expression, developmental state and outcome. Integration with chromatin topology analyses enabled elucidation of multiple mechanisms of enhancer deregulation that involve enhancers and genes in a subtype-specific fashion. We show that the immunophenotypically-described, high-risk entity of early T-cell precursor ALL is superseded by a broader category of leukemias of variable immunophenotype with diverse genomic alterations of a core set of genes encoding regulators of hematopoietic stem cell development. Numerous genetic alterations and disease subtypes emerged as independent predictors of survival and treatment failure in univariable and multivariable outcome models. These findings provide a roadmap for the classification, risk stratification and mechanistic understanding of this disease.

  Study EGAS50000000016

• CSER: Evaluating Utility and Improving Implementation of Genomic Sequencing for Pediatric Cancer Patients in the Diverse Population and Healthcare Settings of Texas: The KidsCanSeq Study

  Through this Clinical Sequencing Evidence-Generating Research (CSER) with Enhanced Diversity project we are completing a clinical study (The Texas KidsCanSeq Study) comparing the results of targeted cancer panel sequencing versus genome-scale testing in pediatric cancer patients across diverse clinical settings. We will compare the targeted pediatric cancer panel to germline whole exome sequencing (WES) of unselected childhood cancer patients. We will also compare an RNA/DNA targeted pediatric cancer panel versus WES, transcriptome sequencing and copy number array of FFPE tumor samples for the subset of patients with high-risk tumors. Exome sequencing is performed from a blood or saliva sample of the pediatric age (0-18) patient. We are building on our success completing the CSER program BASIC3 exome sequencing trial (which included 60% Hispanic and African-American patients from a single large academic center) in this large multi-institutional study of an even more diverse patient population from six pediatric oncology healthcare settings across Texas. Data from the Texas KidsCanSeq study will be submitted through the CSER Data Coordinating Center for access in NIH-supported databases.

  Study phs002378

• NHLBI TOPMed: Trans-Omics Analysis for Congestive Heart Failure (TOPCHeF)

  Heart failure (HF) is a serious, common, morbid condition that has a huge public health impact. In 2012 alone, there were >1M hospital discharges and >1.7M outpatient visits where HF was the principal diagnosis. HF is the most common hospital discharge diagnosis of the elderly and led to costs in excess of $30B in 2012. Unfortunately, HF therapies have not impacted the 50% 5-year mortality over the past two decades. Our laboratory focuses on cardiomyopathies (CMs) and HF. Dilated cardiomyopathy (DCM) has been a main focus of our laboratory and is the first and third most frequent cause of heart transplantation and HF, respectively. Attention is shifting from the mere identification and cataloging of CM/HF genes and mutations to understanding the molecular and functional cellular processes that drive HF. In this study, we will utilize whole genome sequencing (WGS) and transcriptome analysis of left ventricle samples from adult and pediatric samples from heart banks at the University of Colorado Anschutz Medical Campus and the Children's Hospital Colorado to develop a complete understanding of left ventricular biology and a partial understanding of HF inferred through the lens of a single-chamber perspective.

  Study phs002038

• Spatial multi-omic map of human myocardial infarction

  Myocardial infarction is a leading cause of mortality worldwide 1 . While advances have been made in acute treatment, an incomplete understanding of remodelling processes has limited the effectiveness of therapies to reduce late-stage mortality 2 . Here, we generate an integrative high- resolution map of human cardiac remodelling after myocardial infarction using single-cell gene expression, chromatin accessibility, and spatial transcriptomic profiling of multiple physiological zones at distinct time points in myocardium from myocardial infarction and control patients. Multimodal data integration allowed us to evaluate cardiac cell-type compositions at increased resolution, yielding insights into changes of the cardiac transcriptome and epigenome through the identification of distinct tissue structures of injury, repair and remodelling. We identified and validated disease-specific cardiac cell-states of major cell-types and analysed them in their spatial context, evaluating their dependency on other cell-types. Our data elucidates molecular principles of human myocardial tissue organisation, recapitulating a gradual cardiomyocyte and myeloid continuum following ischemic injury. In total, our study provides an integrative molecular map of human myocardial infarction and represents an essential reference for the field and paves the way for advanced mechanistic and therapeutic studies of cardiac disease.

  Study EGAS00001006330

• scRNA-seq of HSPC treated with gemcitabine and carbplatin

  The study used cryopreserved hematopoietic stem and progenitor cells (HSPCs) harvested from one patient with chronic myelogenous leukemia (CML). The cells were thawed and acclimatized for 48 hours in StemMACS HSC Expansion Media XF (Miltenyi Biotec) supplemented with StemMACS HSC Expansion Cocktail (Miltenyi Biotec) at 37°C in a humidified atmosphere containing 5% CO2. 4 samples of 2000000 HSPCs in 2 ml media each were then prepared and treated for 24 hours: carboplatin-high: 150 µg/ml carboplatin carboplatin-low: 18.75 µg/ml carboplatin gemcitabine: 25 ng/ml gemcitabine control: no drug Single-cells were subsequently extracted using the ddSEQ™ Single-Cell Isolator (Bio-Rad) and later sequenced using the SureCell™ Whole Transcriptome Analysis 3' Library Prep Kit (Illumina) on the NextSeq 500 System (Illumina) using the NextSeq 500/550 High Output Kit v2.5 150 Cycles (Illumina) all following the manufacturer's instructions. FASTQ-files were then processed following the ddSeeker (Romagnoli, D., et al., BMC Genomics 2018, doi:10.1186/s12864-018-5249-x) and Drop-seq (Macosko, E.Z., et al., Cell 2015, doi:10.1016/j.cell.2015.05.002) protocols for processing scRNA-seq data to yield the final digital gene expression for each cell.

  Study EGAS00001004381

• Cross-tissue transcriptomic analysis of human secondary lymphoid organ residing ILC3 reveals a default quiescent state in the absence of inflammation

  A cross tissue transcriptional comparison of human ILC3 isolated from non-inflamed lymph nodes (LN) and spleens, inflamed tonsils and the peripheral blood (PB). Using uniform gating and high-purity cell-sorting, ILC3 were sorted as Lineage(CD3,CD19,CD34,CD14,CD94)-CD45intCD127+CRTH2-CD117+. From LN, spleen, tonsils and PB, NKp44- ILC3 were isolated and, in addition, NKp44+ ILC3 were sorted from spleen and tonsils. RNA quality was measured on a RNA 6000 Pico Kit (Agilent Technologies) using a 2100 Bioanalyzer (Agilent Technologies). 100 pg high-quality RNA was isolated and cDNA was generated using the SMART-Seq (v3) Ultra Low Input RNA Kit (Clontech) with 15 cycles of amplification. Amplified and Covaris-fragmented cDNA was quality-checked on a High Sensitivity DNA chip (Agilent Technologies) and further processed according the TruSeq Nano DNA Library Preparation Kit (Illumina). Data was processed as follows: SMARTer adapters were trimmed with cutadapt and the resulting sequences were aligned to the human RefSeq transcriptome using 14 TopHat2 (Kim et al., 2013). Normalization and quantification was performed using Cufflinks (Trapnell et al., 2012). FPKM counts were determined per gene with HTSeq-count.

  Study EGAS00001002636

• Whole genome sequencing of Ewings Sarcoma

  Sarcomas are cancers of the bone and soft tissue often defined by their gene fusions. However, the timing, context, and processes by which these pathogenic fusions arise are unknown. We explored this in Ewing sarcoma, a cancer driven by EWSR1-ETS fusions, with very few cooperating mutations. Combining whole-genome sequencing with enhanced informatics, we found that the EWSR1-ETS fusion arose from striking rearrangement clusters in 42% of cases (52/124). Notably, these were organized in loops that universally contained the fusion at their center, while also weaving up to 18 genes together with it. We found the same pattern of rearrangements in three additional types of sarcoma. From these data, we define a new signature for sarcoma fusions that precedes other somatic changes, in the earliest replicating DNA of the genome. This dramatic, sudden process impinges on many genes – generating multiple coding changes that profoundly affect the transcriptome, with the disease-defining gene fusion at its core. These rearrangement loops emerge in an early ES clone from which both the primary tumor and the lethal relapse emerged, and then evolved in parallel until clinically detected.

  Study EGAS00001003385

• Linking the epigenetic landscape in chronic lymphocytic leukemia to deregulated chromatin networks

  Aberrant chromatin features and epigenetic signaling emerge as an important part of the tumor disease state in chronic lymphocytic leukemia (CLL). However, an integrative analysis of the malignant chromatin landscape is currently missing. Here, we mapped DNA-methylation, nucleosome position, 7 histone modifications, ATAC-seq and the transcriptome in primary CD19+ sorted B-cells from the peripheral blood of CLL patients in comparison to non-malignant lymphocytes of healthy donor reference samples. On the > 50 kb scale we identified global differences with respect to DNA methylation, nucleosome positioning and histone modifications in CLL. Furthermore, a chromatin state annotation was developed to identify deregulated chromatin features of promoters and enhancers in CLL. By integrating these findings with an ATAC-seq based transcription factor binding analysis we identified a set of promoters and enhancers specific to CLL that were enriched in certain transcription factors binding motifs and genes of the BCR signaling pathway. Thus, our study provides an in-depth map of the CLL chromatin landscape and links chromatin state changes at promoters and enhancers to deregulated pathways.

  Study EGAS00001002518

• Pharmacogenomic analysis of patient-derived tumor cells in gynecologic cancers

  Gynecologic malignancy is one of the leading causes of mortality in female adults worldwide. Comprehensive genomic analysis has revealed a list of molecular aberrations that are essential to tumorigenesis, progression, and metastasis of gynecologic tumors. However, targeting such alterations has frequently led to treatment failures due to underlying genomic complexity and activation of various tumor cell survival pathway molecules. A compilation of molecular characterization of tumors with pharmacological drug response is the next step towards clinical application of patient-tailored treatment regimens. Toward this goal, we have established a library of 139 gynecologic tumors including cervical, endometrial, and epithelial ovarian cancers (EOCs) and uterine sarcomas that were genomically and/or pharmacologically annotated and explored dynamic pharmacogenomic associations against 37 molecularly targeted drugs. We discovered lineage-specific drug sensitivities based on subcategorization of gynecologic tumors and identified TP53 mutation as a molecular determinant that elicit therapeutic response to poly (ADP-Ribose) polymerase (PARP) inhibitor. We further identified transcriptome expression of inhibitor of DNA biding 2 (ID2) as a potential predictive biomarker for treatment response to olaparib. Together, our results demonstrate potential utility of rapid drug screening combined with genomic profiling for precision treatment of gynecologic cancers.

  Study EGAS00001003556

• An Atlas of Cells in the Human Tonsil

  Palatine tonsils are secondary lymphoid organs representing the first line of immunological defense against inhaled or ingested pathogens. Here, we provide a comprehensive census of cell types forming the human tonsil by applying single cell transcriptome, epigenome, proteome and adaptive immune repertoire as well as spatial transcriptomics, resulting in an atlas of >350,000 cells. We provide a glossary of over one hundred annotated cell types and states, and disentangle gene regulatory mechanisms that drive cells through specialized lineage trajectories. Exemplarily, we stratify multiple tonsil-resident myeloid slancyte subtypes, establish a distant BCL6 superenhancer as locally active in both follicle-associated T and B cells, and describe SIX5 as a potentially novel transcriptional regulator of plasma cell maturation. Further, our atlas is a reference map to understand alterations observed in disease, here we discover immune-phenotype plasticity in tumoral cells and microenvironment shifts of mantle cell lymphomas (MCL). To facilitate such reference-based analysis, we develop HCATonsilData and SLOcatoR, a computational framework that provides programmatic and modular access to our dataset; and allows the straightforward annotation of future single-cell profiles from secondary lymphoid organs.

  Study EGAS00001006375

• Tumor transcriptome profiling from the OAK and POPLAR randomized clinical trials of atezolizumab in 2L NSCLC

  This dataset includes full tumor transcriptomes from 891 advanced NSCLC tumors. These data originate from pre-treatment samples from two large randomized clinical trials for second-line non-small cell lung cancer (POPLAR and OAK). The patients in these trials were treated with either the PD-L1 inhibitor atezolizumab or chemotherapy.

  Dataset EGAD00001007703

• Pan-neuroblastoma analysis reveals age- and signature-associated driver alterations

  Neuroblastoma is a pediatric malignancy with heterogeneous clinical outcomes depending on age and other factors. To better understand neuroblastoma pathogenesis, here we analyze whole-genome, whole-exome and/or transcriptome sequencing data from 702 neuroblastoma samples, half of which are new data. Over 95% of samples harbor at least one recurrent driver alteration and most aberrations, including MYCN, ATRX, and TERT alterations, differ in frequency by age. MYCN alterations occur at median 2.3 years of age, TERT at 3.8 years, and ATRX at 5.6 years, suggesting age-specific susceptibility to genetic alterations. Mutational signature analysis shows that reactive oxygen-species (ROS)-induced mutations are the most common cause of single nucleotide variant (SNV) drivers in neuroblastoma, including most ALK and Ras pathway SNVs. ROS-induced mutagenesis is both an early event, as it causes truncal variants, and continuous as it also induces relapse-specific mutations. ROS-induced mutations are more abundant in neuroblastomas with MYCN amplification, 17q gains, and increased expression of mitochondrial ribosome genes. We observe recurrent FGFR1 N546K or internal tandem duplication variants in 6 patients and ALK N-terminal structural alterations in 5 samples, identifying additional patients amenable to precision therapy.

  Study EGAS00001003931

• Impact of allogeneic umbilical-cord derived mesenchymal stromal cells on B-cell scRNAseq in patients with systemic lupus erythematosus

  The impact of MSC(UC) on peripheral B cells from Systemic Lupus Erythematosus (SLE) patients was studied by 10X scRNAseq. This scRNAseq study encompassed 3 SLE patients at 3 time points: before or after (1 month, and 3 months) MSC injection in order to analyze B cell subsets and their DEG. The aim of this study was to observe the potential changes of B cell subsets after MSC(UC) injection in SLE patients.

  Study EGAS50000000325

• Single-cell and spatial atlas of steatotic liver disease-related hepatocellular carcinoma

  This study consists of the spatial transcriptomics data generated by : 1. Visium CytAssist Spatial Gene Expression for FFPE (10x) for steatotic liver disease-associated hepatocellular carcinoma (SLD-HCC) (n=7) and non-SLD-HCC (n=5) 2. CosMxTM Human Universal Cell Characterization RNA Panel (1000-plex); NanoString, USA for n=4 SLD-HCC and n=4 non-SLD-HCC. The goal of this data is to compare SLD-HCC vs non-SLD-HCC as well as response to immunotherapy

  Study EGAS50000001034

• Establishment of Human Trophoblast Stem Cells from Term Smooth Chorion

  Human trophoblast stem (TS) cells, which were established from blastocysts and first-trimester placental villi, can differentiate into the all trophoblastic subtypes, extravillous trophoblast (EVT) cells and syncytiotrophoblast (ST) cells. We newly generated human TS cells from the term smooth chorion (Ch-TS cells). They has the potential to differentiate into both ST and EVT cells as same as human TS cells derived from early placental villi. The transcriptomic profile of Ch-TS cells is also similar to conventional human TS cells.

  Study JGAS000777

• Epigenome analysis of human trophoblast stem cells

  Trophoblast cells play an essential role in the interactions between the fetus and mother. Mouse trophoblast stem (TS) cells have been derived and used as the best in vitro model for molecular and functional analysis of mouse trophoblast lineages. However, attempts to derive human TS cells have so far been unsuccessful. In this study, we derived human TS cells from human blastocysts. Epigenome analysis revealed that the human TS cells maintained epigenome profiles similar to those of primary trophoblast cells. JGA submission accessions: JGA000122,JGA00000000122

  Study JGAS000112

• Spatial Profiling of Patient-Matched HER2 Positive Gastric Cancer Reveals Resistance Mechanisms to Trastuzumab and Trastuzumab Deruxtecan Sequencing

  HER2-positive gastric cancer (HER2+ GC) exhibits significant intra-tumoral heterogeneity and frequent development of resistance to HER2-targeted therapies. This study aimed to characterize the spatial tumor microenvironment (TME) and identify mechanisms of resistance to HER2 blockade including trastuzumab and trastuzumab deruxtecan (T-DXd) in HER2+ GC, with the goal of informing novel therapeutic strategies. We performed spatial transcriptomics on pre- and post-treatment samples from patients with HER2+ metastatic GC who received trastuzumab-based therapy.

  Study EGAS50000000636

• Hip OA Functional Genomics

  The aim of this work is to apply an integrated systems approach to understand the biological underpinnings of hip osteoarthritis that culminates in the need for total joint replacement (TJR). This study is a feasibility pilot that integrates functional genomics data from diseased and non-diseased tissues of OA patients who have undergone TJR. For each tissue, we characterised epigenetic marks (methylation), gene transcription (RNASeq) and expression (quantitative proteomics). We also generated genotype data on the HumanCoreExome array for each individual.

  Study EGAS00001002483

• Knee_OA_Functional_Genomics

  The aim of this work is to apply an integrated systems approach to understand the biological underpinnings of knee osteoarthritis that culminates in the need for total joint replacement (TJR). This study is a feasibility pilot that integrates functional genomics data from diseased and non-diseased tissues of OA patients who have undergone TJR. For each tissue, we characterised epigenetic marks (methylation), gene transcription (RNASeq) and expression (quantitative proteomics). We also generated genotype data on the HumanCoreExome array for each individual.

  Study EGAS00001001899

• Lung_Cell_Atlas__Paediatric_RNA

  Single cell sequencing will be carried out by multiome profiling (RNAseq and ATACseq). Additonal modalities may be examined. Spatial profiling may involve Visium, Curio and other technologies. This data set will feed into a larger analysis of the human lungs over development, that aims to detail all the cell types of the human lungs and airways and will extend current knowledge by providing chromatin accessibility data that will allow us to link GWAS data and identify regulatory networks and then compare these against fetal and adult data sets

  Study EGAS00001008299

• Lung_Cell_Atlas__Paediatric_Spatial

  Single cell sequencing will be carried out by multiome profiling (RNAseq and ATACseq). Additonal modalities may be examined. Spatial profiling may involve Visium, Curio and other technologies. This data set will feed into a larger analysis of the human lungs over development, that aims to detail all the cell types of the human lungs and airways and will extend current knowledge by providing chromatin accessibility data that will allow us to link GWAS data and identify regulatory networks and then compare these against fetal and adult data sets

  Study EGAS00001008300

• Lung cancer organoids addition

  Organoids are self-organizing 3D structures grown from stem cells that recapitulate essential aspects of organ structure and function. Here we describe a method to establish long-term culture conditions of human airway epithelial organoids that contain all major cell populations and allow personalized human disease modelling. We collected macroscopically inconspicuous lung tissue from non-small-cell lung cancer (NSCLC) patients undergoing medically indicated surgery and isolated epithelial cells to engineer 3D organoids. We exploit the potential to derive sub-clones from AOs to demonstrate the feasibility of CRISPR gene editing. Finally, we show that AOs readily allow modelling of viral infections such as RSV and for the first time demonstrate the possibility to study neutrophil-epithelium interaction in an organoid model. Taken together, we anticipate that human AOs will find broad applications in the study of adult human airway epithelium in health and disease.

  Dataset EGAD00001004943

• Total XVI RNAseq

  RNAseq data of total TXVI samples

  Dataset EGAD00001007530