3924 results for "RNA AND sequencing OR transcriptome"

in 58.07 milliseconds.

• PEACE melanoma 14

  Understanding the evolutionary pathways to metastasis and resistance to immune checkpoint inhibitors (ICI) in melanoma is critical for improving outcomes. Here we present the most comprehensive intra-patient metastatic melanoma dataset assembled to date as part of the PEACE research autopsy programme, including exome, panel-sequenced, RNA-seq, and single-cell whole-genome sequencing samples from 14 ICI-treated patients. The main goals of the project are to decipher the evolutionary dynamics of melanoma metastases and to elucidate mechnisms of resistance to therapies.

  Study EGAS00001007081

• Dissecting the Spatial Heterogeneity of Single Circulating Tumor Cells in Hepatocellular Carcinoma

  The dismal outcome of hepatocellular carcinoma (HCC) is closely associated with intra- and extrahepatic metastases, which have been proposed to be initiated by circulating tumor cells (CTCs). However, the plasticity of gene expression and immune evasion mechanisms of CTCs during systemic circulation are not well defined. Here, we determined intra- and inter-vascular transcriptional heterogeneity within the circulatory system using single-cell RNA-sequencing of 113 CTCs isolated from four key vascular sites along their dissemination route in ten HCC patients.

  Study EGAS00001005204

• scRNAseq of human primary nasal epithelium differentiated at air-liquid interface exposed to SARS-CoV2

  The nasal epithelium is a plausible entry point for SARS-CoV-2, a site of pathogenesis and transmission, and may initiate the host response to SARS-CoV-2. Antiviral interferon responses are critical to outcome of SARS-CoV-2. Yet little is known about the interaction between SARS-CoV-2 and innate immunity in this tissue. Here we applied single-cell RNA sequencing and proteomics to a primary cell model of human primary nasal epithelium differentiated at air-liquid interface.

  Study EGAS00001005633

• Cold Ischemia Study

  This study aimed to evaluate the impact of cold ischemia time on the expression of cancer-related genes, particularly those involved in hypoxia, apoptosis, and epithelial-to-mesenchymal transition (EMT). We performed RNA sequencing on 54 normal colon mucosa samples from nine patients undergoing colorectal cancer surgeries, freezing samples at predefined intervals ranging from 0 to 60 minutes. A total of 44 differentially expressed genes (DEGs) (p < 0.05) were identified when comparing samples frozen immediately (T0) with those frozen after 60 minutes (T5).

  Study EGAS00001008233

• Detection of isoforms and genomic alterations by high-throughput full-length single-cell RNA sequencing in HGSOC

  Understanding the complex background of cancer requires genotype-phenotype information in single-cell resolution. Long-read single-cell RNA sequencing (scRNA-seq), capturing full-length transcripts, lacked the depth to provide this information so far. Here, we increased the PacBio sequencing depth to 12,000 reads per cell, leveraging multiple strategies, including artifact removal and transcript concatenation, and applied the technology to samples from three human ovarian cancer patients. Our approach captured 152,000 isoforms, of which over 52,000 were novel, detected cell type- and cell-specific isoform usage, and revealed differential isoform expression in tumor and mesothelial cells. Furthermore, we identified gene fusions, including a novel scDNA sequencing-validated IGF2BP2::TESPA1 fusion, which was misclassified as high TESPA1 expression in matched short-read data, and called somatic and germline mutations, confirming targeted NGS cancer gene panel results. With multiple new opportunities, especially for cancer biology, we envision long-read scRNA-seq to become increasingly relevant in oncology and personalized medicine.

  Study EGAS00001006807

• RNA sequencing of surgically removed lung adenocarcinoma afterwards treated with immune checkpoint inhibitors

  Patients with lung adenocarcinoma (LUAD) from The Cancer Genome Atlas (TCGA) database were enrolled in the training cohort to establish a prognostic signature based on the expression of tumor-specific amino acid metabolism related genes. The established signature was further investigated against an original cohort, KCC-ICI, of chemotherapy combined with immune checkpoint inhibitors. The signature consisting of nine genes, KYNU, PSPH, PPAT, MIF, GCLC, ACAD8, TYRP1, ALDH2, and HDC, could effectively stratify the OS in LUAD patients. The KCC-ICI cohort confirmed the predictive ability of the established signature in the clinical response to immune checkpoint blockade therapy, which correlated with the infiltration of immune cells (e.g., T lymphocytes and nature killer cells). We discovered that the high signature risk score patients showed a significantly lower concentration of plasma-free ??-aminobutyric acid (AABA).

  Study JGAS000675

• Dynamic Evolution of Fibroblasts Revealed by Single Cell RNA Sequencing of Human Pancreatic Cancer

  Understanding the constituents of the pancreatic ductal adenocarcinoma (PDAC) microenvironment may illuminate more efficacious targets for treating this aggressive malignancy. However, the compositional changes occurring in untreated and treated PDAC relative to both normal and inflamed pancreas have not been well characterized. To provide a more comprehensive understanding of the PDAC tumor microenvironment relative to the non-cancerous pancreas, we performed single-cell expression profiling (10X Genomics Chromium) on samples of upfront resectable PDAC, FOLFIRINOX-based treated PDAC, chronic pancreatitis, and normal pancreas specimens from 19 patients. Spatial gene expression profiling (10X Genomics Visium) was performed to gain additional insight into cell populations. Our analysis revealed that fibroblasts are central mediators of cell-cell communication in both inflamed and malignant settings and defined unique roles for these cell populations in different disease contexts.

  Study phs003751

• Multi-omics data of 1000 Inflammatory Bowel Disease patients

  Portal available at https://1000ibd.org Inflammatory bowel disease (IBD) is a chronic complex disease of the gastrointestinal (GI) tract. Patients with IBD can experience a wide range of symptoms, but the pathophysiological mechanisms that cause these individual differences in clinical presentation remain largely unknown. In consequence, IBD is currently classified into subtypes using clinical characteristics. If we are to develop a more targeted treatment approach, molecular subtypes of IBD need to be discovered that can be used as new drug targets. To achieve this, we need multiple layers of molecular data are generated from the same IBD patients.We initiated the 1000IBD project to prospectively follow more than 1000 IBD patients from the Northern provinces of the Netherlands. For these patients, we have collected a uniquely large number of phenotypes and generated multi-omics profiles. To date, 1,215 participants have been enrolled in the project and enrolment is on-going, with 609 patients being present in the first data release. Phenotype data collected for these participants includes information on dietary and environmental factors, drug responses, and adverse drug events. Genome information has been generated using genotyping (ImmunoChip, Global Screening Array and HumanExomeChip) and sequencing (whole exome sequencing and targeted resequencing of IBD susceptibility loci), transcriptome information generated using RNA-sequencing of intestinal biopsies and microbiome information generated using both sequencing of the 16S rRNA gene and whole genome shotgun metagenomic sequencing.All molecular data generated within the 1000IBD project will be shared in multiple data on the European Genome-Phenome Archive (www.ega-archive.org). The first data release, will contain basic phenotypes for 609 participants, genotypes of 314 participants, gut microbiome data generated by tag sequencing the 16S gene of feces from 315 participants and intestinal biopsies from 107 participants, and gut microbiome metagenomic sequencing of feces of 355 participants . Future releases will comprise many more additional phenotypes and -omics data layers. 1000IBD data can be used by other researchers as a replication cohort, a dataset to test new software tools, or a dataset for applying new statistical models.

  Study EGAS00001002702

• Ex vivo RNA-seq in moderate COVID-19 monocytes

  This dataset was used to compare gene expression profiles of ex vivo isolated classical CD14+ monocytes from patients with moderate COVID-19 to those of healthy individuals. Blood samples were taken from patients with moderate COVID-19 admitted to hospitals in London (Hammersmith Hospital, Charing Cross Hospital, Saint Mary’s Hospital) 3-14 days after disease onset and 0-2 days after hospitalization and positive PCR, and before study treatment initiation. Moderate patients displayed mild or moderate COVID-19 pneumonia, defined as grade 3 or 4 WHO severity. Samples were collected from March 2020 to February 2021. Healthy donors were Imperial College staff with no prior diagnosis of or recent symptoms consistent with COVID-19, and where possible, were matched in age and sex distribution with COVID-19 patients. None of the participants of this study were COVID-19 vaccinated. Peripheral blood mononuclear cells (PBMCs) were isolated by Ficoll Hypaque (GE Healthcare) gradient centrifugation <4 hours after blood collection. CD14+ monocytes were isolated using a positive selection magnetic sorting kit (StemCell Technologies, UK) from total PBMC and stimulated with vehicle, UV-inactivated SARS-CoV-2 (CoV-2). RNA was isolated using the RNeasy Micro Plus Kit (QIAGEN) following the manufacturer’s guidelines. RNA-sequencing was performed by the Oxford Genomics Centre. PolyA-enriched strand- specific libraries were prepared using NEBNext Ultra II Directional RNA Library Prep Kits (Illumina). All samples were pooled together and 150bp PE reads were sequenced on a Novaseq 6000 system.

  Dataset EGAD00001009800

• Spatial transcriptomic data of breast cancer

  Fastq files from spatial transcriptomic of breast cancer coming from 8 Breast cancer sections. Sample preparation: frozen BC samples were chosen based on tissue structure and RNA quality (RIN > 8). The “Visium Spatial Tissue Optimization Slide and Reagent Kit” (10X Genomics; #PN-1000193) was then used to optimize permeabilization conditions for BC tissues. Briefly, sections were fixed, stained and then permeabilized at different time points to capture mRNA, and the reverse transcription was performed to generate fluorescently labeled cDNA. The permeabilization time that resulted in the highest fluorescence signal with the lowest background diffusion was chosen. The best permeabilization time for BC tissue was 18 min. Cryostat sections of 10 μm of thickness were cut and placed on Visium Spatial Gene Expression slides (10X Genomics, PN-1000184). The slide was incubated for 1 min at 37°C, then fixed with methanol for 30 min at -20°C followed by Hematoxylin and Eosin (H&E) staining and images were taken under a high-resolution microscope. After imaging, the coverslip was detached by holding the slide in water and the slide was mounted in a plastic slide cassette. The spatial gene expression process, including tissue permeabilization, second strand synthesis and cDNA amplification, was performed according to the manufacturer’s instructions (10X Genomics; #CG000239). cDNA quality was next assessed using Agilent High sensitivity DNA Kit (Agilent, #5067-4626). The spatial gene libraries were constructed using Visium Spatial Library Construction Kit (10X Genomics, PN-1000184).

  Dataset EGAD50000000322

• Identifying transcriptional programs underlying anti-EGFR small molecule response and resistance with TraCe-seq

  To QC the TraCe-seq strategy, single-cell RNA-seq libraries were generated from a variety of human cancer cell lines transduced with the TraCe-seq library to validate the TraCe-seq strategy. Specifically, 5 different cell lines (PC9, MCF-10A, MDA-MB-231, NCI-H358, and NCI-H1373) were each transduced with a unique TraCe-seq barcode. The transduced cells were selected with puromycin only, dissociated to single cell suspensions, and then mixed together. The complex mixture of the 5 cell lines was profiled by 10X scRNA-seq. Furthermore, transduced NCI-H1373 cells were sorted by FACS to enrich for the top 50% of eGFP positive cells, and sorted cells were cultured briefly and used to construct scRNA-seq libraries and profiled by 10x scRNA-seq. To carry out the full TraCe-seq experiment, ~600 PC9 cells carrying unique TraCe-seq barcodes were expanded over 12 doublings to establish the barcoded population. A subset of the barcoded PC9 population was used to generate scRNA-seq libraries and profiled by 10x scRNA-seq prior to treatment to establish a baseline transcription profile for each barcoded clone. The rest of the cells were then treated for four days with 1 µM erlotinib, 1 µM GNE-069, or 1 µM GNE-104 respectively. scRNA-seq libraries were then generated form the treated cells and profiled by 10x scRNA-seq.

  Dataset EGAD00001007872

• Raw sequencing data from low-input chromosome conformation capture in CD4+ T cells

  This dataset contains raw sequencing data from low-input PCHi-C in human primary CD4+ T cells isolated from healthy donors. The data are released as paired-end Illumina FASTQ files. Promoter Capture Hi-C used DpnII digestion and Tn5-based low-input library preparation, followed by targeted capture with custom-designed biotinylated RNA probes targeting most of the annotated gene promoters.

  Dataset EGAD50000001873

• DNA sequening

  The dataset consist of DNA and RNA sequencing results and metadata of the samples. All sample numbers starting with 6716 are tumor samples which has been sequenced using WES (see BAM files). It concerns biopsies of metastatic lesions from patients with BRAFV600 mutated melanoma, obtained before, during and after the study treatment (see samples metadata) and in some cases blood for germline mutation analysis. Sequencing is performed using the Illumina Novaseq 6000 system.

  Dataset EGAD50000000382

• DLK1 Distinguishes Subsets of NF1-Associated Malignant Peripheral Nerve Sheath Tumors with Divergent Molecular Signatures

  Study Design and Aims We aimed to investigate the molecular mechanisms underlying the malignant transformation of pre-existing neurofibromas (PNST) to malignant peripheral nerve sheath tumors (MPNST) in individuals with neurofibromatosis type 1 (NF1). Our primary focus was on the role of DLK1 in this transformation process and its potential as a biomarker for diagnosis, risk assessment, and therapeutic stratification. Population InformationThis study consisted of a case set of peripheral nerve sheath tumor specimens, including plexiform neurofibromas, atypical neurofibromas, and MPNSTs, acquired under IRB approval at our institution. The majority of the subjects had neurofibromatosis type 1. Principal Findings DLK1 Overexpression: The study found that DLK1 is significantly increased in MPNST compared to non-malignant neurofibromas.Early Marker: DLK1 overexpression may precede histological changes indicative of malignancy.Serum Levels: Higher serum levels of DLK1 were observed in both mice and humans with MPNST.Molecular Stratification: Divergent levels of DLK1 expression identified distinct MPNST subsets with unique molecular characteristics and potential therapeutic targets.Clinical Implications: Overexpression of DLK1 was associated with the reactivation of embryonic signatures, an immunosuppressive microenvironment, and poorer overall survival in NF1-MPNST patients. Data Availability Whole exome sequencing, bulk RNA sequencing, and single-cell RNA sequencing data from this study will be made available through the database of Genotypes and Phenotypes (dbGaP) to support further research and validation studies.

  Study phs003835

• RNA seq on 19 samples of Radiation-Induced Meningiomas

  Purpose: Majority of pediatric cancers require the irradiation of the central nervous system (CNS), and as more patients survive into adulthood from improved oncological therapy the sequelae of brain radiation are increasing in prevalence. Radiation-induced meningiomas (RIMs), one such secondary effect, demonstrate a clinically more aggressive behaviour than sporadic meningiomas (SMs). We aimed to describe the genomic mutational landscape of RIMs.Methods: We analyzed a principal cohort of 18 RIMs, with 31 RIMs overall, from patients who received childhood radiation therapy and 30 SMs, as a comparator population. We performed a multiplatform integrative genomic analysis; including methylation, whole exome and RNA sequencing. Results: RIMs exhibited a five-fold increase in copy number alterations, commonly the loss of chromosome 1p (17/18 RIMs) and 22q (17/18 RIMs), which was significantly more than observed in sporadic meningiomas. Furthermore, RNA sequencing data revealed an NF2 gene fusion event in 35.3% of RIMs. In all 6 cases, there was a complete NF2 exon spliced into a complete exon of a reciprocal gene, suggesting that the breakpoints of genomic rearrangement are intronic. All tumours with the NF2 fusion also possessed monosomy of chromosome 22q, rendering the cells with homozygous disruption of NF2. Clinically, RIMs with the NF2 fusion exhibited ill-defined borders and a tendency to develop in anatomic frontal location. Also, targeted sequencing panel confirmed that RIMs had fewer nonsynonymous NF2 mutations (6.5% vs. 30% in SM) and absence of mutations in TRAF7, SMO, KLF4, PIK3CA and AKT1, genes traditionally involved in SMs.Conclusion: Our study demonstrates that RIMs have distinct genomic drivers of oncogenesis as compared to SMs, specifically NF2 inactivation through fusion event. Radiation therapy possibly triggers genomic structural rearrangements through error-prone repair of double-stranded DNA breaks.

  Study EGAS00001002318

• Lymphoma_primary_patient_drug_perturbed_RNASeq_samples

  3'-end low-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 inhibitors (ibrutinib, duvelisib, everolimus, trametinib, nutlin-3a, I-BET-762, MK2206, selinexor, compound 26, and a combination of ibrutinib and compound 26). Sequencing was performed on the Illumina HiSeq4000. The dataset contains FASTQ files.

  Dac EGAC50000000578

• H3Africa CAfGEN Exome

  Whole Exome Sequencing data from a retrospective paediatric HIV-disease progression cohort defined on the World Health Organization's criteria for paediatric HIV progression. Data comprises of BAM and VCF files for 314 participants from 2 countries: Botswana and Uganda. DNA and RNA samples are linked in bio-repository.

  Dataset EGAD00001006224

• RNA-Seq of 584 DLBCL Cases of Non-China Cohort from Phoenix Clinical Trial

  Standard RNA-Seq datasets. Check the associated paper for more details.

  Dataset EGAD00001008131

• Gene expression signatures associated with chronic endometritis revealed by RNA sequencing

  Chronic endometritis (CE) is a persistent inflammatory condition of the endometrium characterized by the infiltration of plasma cells. CD138 immunohistochemistry is considered to improve the CE diagnosis rate. Using the number of CD138-positive cells equal or greater than five as a diagnostic criterion for CE, we identified 24 CE and 33 non-CE cases among women with infertility. We conducted RNA-sequencing analysis for these 57 cases in total as an attempt to elucidate the molecular pathogenesis of CE and to search for new biomarkers for CE. By comparing CE and non-CE groups, we identified 20 genes upregulated in the endometria of CE patients, including 12 immunoglobulin-related genes and eight non-immunoglobulin genes as differentially expressed genes. The eight genes were MUC5AC, LTF, CAPN9, MESP1, ACSM1, TVP23A, ALOX15, and MZB1. By analyzing samples in the proliferative and secretory phases of the menstrual cycle separately, we also identified four additional non-immunoglobulin genes upregulated in CE endometria: CCDC13 by comparing the samples in the proliferative phase, and OVGP1, MTUS2, and CLIC6 by comparing the samples in the secretory phase. Although the genes upregulated in CE may serve as novel diagnostic markers of CE, many of them were upregulated only in a limited number of CE cases showing an extremely high number of CD138-positive cells near or over one hundred. Exceptionally, TVP23A was upregulated in the majority of CE cases regardless of the number of CD138-positive cells. The upregulation of TVP23A in the endometria of CE cases may reflect the pathophysiology of a cell-type or cell-types intrinsic to the endometrium rather than the accumulation of plasma cells. Our data, consisting of clinical and transcriptomic information for CE and non-CE cases, helped us identify gene expression signatures associated with CE.

  Study JGAS000621

• MGHBoston_Molpheno_Closed

  This dataset contains Whole Genome Sequencing and, if available, RNA-sequencing and/or ATAC-sequencing data of 17 lymphoblastoid cell lines derived from patients with complex genomic rearrangements. Patients have phenotypes in category of intellectual disability and/or multiple congenital anomalies. Data access is closed.

  Dataset EGAD00001004866

• Whole exome sequencing and RNA sequencing of patient-derived pancreas neoplasm organoids

  Pancreatic cancers arise from two different precursors; intraductal papillary mucinous neoplasms (IPMN) and pancreatic intraepithelial neoplasm (PanIN), while biological differences in cancers originated from them remain obscure. Here, we analyzed their genomic and transcriptomic landscapes using patient-derived organoids.

  Study JGAS000263

• Raw sequencing data for donor and patient fecal samples

  Microbiome analysis was performed on the patient samples collected pre-FMT and on days after FMT, and on samples collected from the FMT donor. Genomic bacterial DNA was extracted from fecal samples using the QIAamp DNA Stool kit (Qiagen, Hilden, Germany), with the addition of a bead-beating lysis step. Genomic 16S ribosomal-RNA V4 variable regions were amplified and sequenced on the Illumina MiSeq platform.

  Dataset EGAD00001004371

• Whole exome sequencing of advanced gastric cancer

  To define the cellular characteristics of malignant ascites of advanced gastric cancer patients and search for therapeutic strategies, we obtained 5 malignant ascites and 1 cerebrospinal fluid from five patients with gastric cancer. We analyzed single-cell RNA-seq data of 180 cells from 4 malignant ascites and 1 cerebrospinal fluid metastasis using Fluidigm® C1™ System. Whole exome sequencing data was also generated from blood or tumor tissue.

  Dataset EGAD00001005740

• Overcoming Clinical Resistance to EZH2 Inhibition Using Rational Epigenetic Combination Therapy

  Essential epigenetic dependencies have become evident in many cancers. Based on functional antagonism between BAF/SWI/SNF and PRC2 in SMARCB1-deficient sarcomas, we and colleagues recently completed the clinical trial of the EZH2 inhibitor tazemetostat, leading to its FDA approval. However, the principles of tumor response to epigenetic therapy in general and tazemetostat in particular remain unknown. Using functional genomics of patient tumors and diverse experimental models, we defined molecular mechanisms of tazemetostat resistance. We found distinct classes of acquired mutations that converge on the RB1/E2F axis, decoupling EZH2-dependent differentiation and cell cycle control. This allows tumor cells to escape tazemetostat-induced G1 arrest despite EZH2 inhibition and suggests a general mechanism for effective EZH2 therapy. Using RNA-sequencing of patient tumor specimens, we identified specific genes as markers of a deficient RB1/E2F axis, which we propose as prospective biomarkers for therapy stratification. This offers a paradigm for rational epigenetic combination therapy suitable for immediate translation to clinical trials.This study was performed on archived tumor tissue collected as part of the above clinical trial at Memorial Sloan Kettering Cancer Center. Patient tumors were classified into "Response" or "Progression" groups based on RECIST 1.1 criteria. "Response" included tumors exhibiting a complete response, partial response, or stable disease. All other tumors were classified under the "Progression" group. Archived frozen tumor samples were weighed and up to 20-30mg were homogenized in RLT buffer, followed by extraction using the AllPrep DNA/RNA Mini Kit (QIAGEN catalog 80204) according to the manufacturer's instructions. RNA was eluted in 13 μL nuclease-free water. After RiboGreen quantification and quality control by Agilent BioAnalyzer, 1 μg of total RNA with DV200 percentages varying from 78% to 100% underwent ribosomal depletion and library preparation using the TruSeq Stranded Total RNA LT Kit (Illumina catalog RS-122-1202) according to instructions provided by the manufacturer with 8 cycles of PCR. Samples were barcoded and sequenced using NovaSeq 6000 in a PE150 mode, with the NovaSeq 6000 S4 Reagent Kit (Illumina). On average, 84 million paired reads were generated per sample and 70% of the data mapped to mRNA. For analysis, read adaptors were trimmed and quality filtered using 'trim_galore' and mapped to GRCh38/hg19 reference genome using STAR v2.7.9 with default parameters.

  Study phs003188

• Whole Blood Transcriptomics of Patients With Melioidosis

  Melioidosis is a neglected tropical infection caused by the Gram negative bacterium Burkholderia pseudomallei that is associated with high mortality rates in southeast Asia. The goal of this study was to a) identify human blood leukocyte transcriptomic features and pathways specific to melioidosis (vs other etiologies of infection), b) identify transcriptomic features and pathways specific to fatal melioidosis, and c) identify transcriptomic predictors of death in patients with melioidosis. This study used clinical data and whole blood leukocyte samples from a subset of participants in the Ubon Sepsis Study, a prospective single-center cohort study conducted at Sunpasitthiprasong Hospital, Ubon Ratchathani, Thailand between 2013 and 2017. Participants in the Ubon Sepsis Study had suspected or documented infection with accompanying systemic manifestations of infection and were enrolled, with blood sampling, within 24 hours of admission to the study hospital. Enrolled patients were followed over time and vital status was determined at 28 days after enrollment. The subset of participants from the parent Ubon Sepsis Study cohort selected for this study was comprised of 164 patients with melioidosis (defined as having a culture of clinical sample positive for B. pseudomallei), 35 patients with Gram negative bacteremia due to either Escherichia coli or Klebsiella pneumoniae, 16 patients with Gram positive bacteremia due to Staphylococcus aureus, and 19 patients who had negative blood cultures and no clinical sample culture-positive for B. pseudomallei. Fifty uninfected control patients with or without diabetes were recruited from the outpatient department and blood donation center at Udon Thani hospital, Udon Thani, Thailand from 2018 to 2019. Blood was collected at the time of enrollment in Tempus Blood RNA tubes. RNA was extracted using the Tempus Spin RNA Isolation kit. RNA sequencing (RNA-Seq) was performed at the University of Washington Northwest Genomics Center. Analysis was performed using a variety of statistical methods. The main finding of the study was that the transcriptomes of melioidosis patients, compared to patients with other infections, were characterized by upregulation of interferon signaling. The transcriptomes of patients with fatal melioidosis were notable for upregulation of inflammatory and type 2 immune responses and downregulation of genes related to T-cell function. A five-gene (EPHB1, SYCP2L, MERTK, IL5RA, and SPOCK1) predictive signature for death in melioidosis was developed.

  Study phs003724

• RNA-sequencing data from metastatic Castration-Resistant Prostate Cancer (mCRPC)

  The goal of this study is to characterize the transcriptional landscape of advanced prostate cancer

  Study EGAS00001005954

• Sequencing data for oesophageal / related samples - Foley, Shorthouse et al (RNA)

  Data supporting: "SMAD4 and KCNQ3 Alterations are Associated with Lymph Node Metastases in Oesophageal Adenocarcinoma" RNAseq (FASTQ files) 6 samples

  Dataset EGAD00001011065

• Kidney tumour_DNA (2018-09-19)

  This is a bulk DNA and RNA sequencing study of human renal tumours . This dataset contains all the data available for this study on 2018-09-19.

  Dataset EGAD00001004346

• Childhood Cancer Data Initiative (CCDI): Pediatric In Vivo Testing Program –Sarcoma, Kidney, and Liver Cancers

  The goal was to complete whole exome sequencing (WES) and RNA sequencing (RNA-Seq) on patient derived xenograft samples. Cancer in children is rare with approximately 15,700 new cases diagnosed annually in children 21 years or younger in the U.S. Through use of multimodality therapy (surgery, radiation therapy, and aggressive chemotherapy), 70% of patients will be 'cured' of their disease, and 5-year Event-Free Survival (EFS) exceeds 80%. Consequently, the number of patients that can be enrolled in phase I/II clinical trials is small, and most patients will have been extensively treated, hence drug/radiation resistant. Thus, preclinical studies that accurately translate into effective clinical therapy are an essential component of pediatric drug development. Our group has contributed to studies in the Pediatric Preclinical Testing Program (PPTP) and Pediatric Preclinical Testing Consortium (PPTC) that have led to clinical studies through Children's Oncology Group (COG). Of importance, we have developed and characterized over 330 Patient Derived Xenografts (PDX), developed from tumors both at diagnosis and relapse, that can be used to facilitate pediatric drug development as directed by FDA under the Research to Accelerate Cures and Equity for Children Act (RACE for Children Act).

  Study phs003160

• Integrated genomic analysis for HCC

  Liver cancer is a common malignancy and is the third cause of cancer-related death in the world and hepatocellular carcinoma (HCC) is the major type of liver cancer, accounting for ~90% of cases. Only 20 ~ 30% of patients can benefit from combined immunotherapy and targeted therapy due to the high inter-tumor heterogeneity of HCC. This work aims to identify homogeneous and robust molecular subtypes in HCC based on a large, homogenous and well-annotated cohort. We performed whole genome/exome sequencing (WGS/WES) and/or RNA sequencing (RNA-seq) on 529 HCC from 461 patients collected mainly in France. Based on the great consistence between genomic and transcriptomic data, we identified 9 robust HCC subtypes mainly based on driver mutations. And we further characterized HCC subtypes using genomic, transcriptomic and clinicopathological features. Among 9 subtypes, 5 subtypes belonged to chromosome instable tumors, while 3 subtypes belonged to chromosome stable tumors. In addition, our subtypes were associated with prognosis and we also found different distributions of subtypes across various features, such as etiology and gender. Our study provided a robust molecular classification based on a large HCC dataset from Western country, it improves our understanding of the mechanisms of carcinogenesis and will facilitate development of genome-based precision medicine in HCC.

  Study EGAS00001007957

• RNA-Seq from PMM2-CDG Patients and Healthy Controls

  Besides the predominant neurological involvement of PMM2-CDG patients, around 20% of patient mortality has been linked to severe infections. However, the immunological dysfunction in PMM2-CDG is not well understood. In this study, we aimed to address this gap and study the molecular mechanisms affected behind immunological issues in PMM2-CDG. Primary skin fibroblasts from three PMM2-CDG patients and three healthy controls were stimulated or not with TNF-alpha and their gene expression was assessed by RNA sequencing. The response to TNF-alpha was characterized based on the differential expressed genes and functional enrichment and and compared between PMM2-CDG and healthy individuais. Gene expression alterations and functional enrichment were further validated by several experimental assays by ELISA, Flow Cytometry and Western Blotting.

  Study phs003313

• WES of precancerous lesions from 10 lynch patients and 3 sporadics

  Raw sequencing data of WES that were obtained from precancerous samples as adenoma and MMR-deficient crypts and paired healthy tissue from MSI CRC patients of which 10 are diagnosed with lynch syndrome and 3 had sporadic cancer. These data were analyzed in order to evaluate microsatellite instability though tumorigenesis and associated to splicing deregulation in MSI tumors RNA.

  Dataset EGAD50000000644

• Primary Cytotoxic T Cell Lymphomas Harbor Recurrent Targetable Alterations in the JAK-STAT Pathway

  Cytotoxic cutaneous T cell lymphomas (CTCLs) are uncommon but highly aggressive cancers of skin-homing cytotoxic T cells. These include the established World Health Organization (WHO) entity primary cutaneous gamma delta T cell lymphomas (PCGDTLs), the provisional WHO entity primary cutaneous CD8+ aggressive epidermotropic T cell lymphoma (PCAETCL), and samples that do not currently fit into a WHO category, referred to as cytotoxic CTCL-NOS (not otherwise specified). In this study, 35 CTCL cases were examined, and 9 PCAETCL cases were confirmed by CD8 expression and full-thickness epidermotropism. Whole genome sequencing (WGS) and bulk RNA sequencing were performed on these samples.  

  Study phs002499

• Mechanisms of Chemotherapy Resistance in T-ALL

  The goals of this study are to unravel the molecular mechanisms underlying leukemic transformation and chemotherapy resistance in T-cell acute lymphoblastic leukemia (T-ALL). Towards this end, a cohort of T-ALL lymphoblast specimens was collected at the time of initial T-ALL diagnosis (prior to the start of therapy) from children enrolled on contemporary clinical trials, Children's Oncology Group study AALL0434 and Dana-Farber Cancer Institute 05-001. Samples were analyzed using targeted exon sequencing and RNA sequencing analysis. Results of these analyses form the basis of studies that have been submitted for publication, and will be linked to this entry once published.

  Study phs001513

• Assessing Individual Head and Neck Squamous Cell Carcinoma Patient Response to Therapy Through Integration of Functional and Genomic Data

  This study combines RNA sequencing (RNASeq), whole exome sequencing (WES), reverse phase protein array (RPPA) and copy number variation (CNV) data, along with a custom high throughput inhibitor assay to characterize tumor cells from patients with head and neck squamous cell carcinoma (HNSCC), in order to identify potential therapy targets on an individual patient basis. The data that will be available through dbGaP include the RNASeq, WES, RPPA and array CNV data for the tumor and matched normal samples. This study represents a proof-of-concept. No treatments were administered to patients as part of this study.

  Study phs003456

• Single-Cell Transcriptomic Characterization of Microscopic Colitis

  Patients with microscopic colitis (MC), chronic diarrhea without histological signs of MC, or unaffected controls were profiled using single-cell RNA sequencing (scRNA-seq; inDrops and 10X Genomics were used). One profiled patient without clinical symptoms was found to have histological signs of MC (asymptomatic MC). Some of the subjects from dbGaP study phs003418 are controls in this study. T-Cell Receptor sequencing (TCR-Seq) was also performed on a subset of patients. Individual transcriptomes were analyzed to characterize the cellular profile associated with MC and search for mediators of disease pathology. Raw reads and processed count matrices will be available through dbGaP.

  Study phs003876

• Dynamics of tumor ecosystems and microbiome in response to neoadjuvant atezolizumab, bevacizumab, and FOLFOX treatment in patients with unresectable colorectal cancer with liver metastasis

  This study aims to explore the effects of neoadjuvant atezolizumab, bevacizumab, leucovorin, 5-fluorouracil, and oxaliplatin (ABFOLFOX) in patients with unresectable colorectal liver metastases (CRLM), focusing on the molecular dynamics of tumor ecosystems (TE) of CRLM and their impact on treatment outcomes. The study comprises two cohorts with CRLM tissue samples analyzed with RNA sequencing and immunohistochemical staining: cross-sectional cohort A (n = 60, CRLM treated with or without neoadjuvant chemotherapy) and prospective cohort B (n = 20 with serial sampling and treated with ABFOLFOX). Shotgun metagenomic sequencing was done for stool samples from cohort B.

  Study EGAS50000000677

• NIBIT-M4 Clinical Trial samples

  Patients (N=14) with unresectable stage III/IV melanoma received escalating doses of guadecitabine 30, 45, or 60 mg/m2/day subcutaneously on days 1 to 5 every 3 weeks, and ipilimumab 3 mg/kg intravenously on day 1 every 3 weeks, starting 1 week after guadecitabine, for four cycles. Patient-wise genome-wide DNA methylation, Whole Exome and RNA sequencing were then performed for samples obtained by surgical removal or fine-needle biopsy at baseline (W0), week 4 (W4) and week 12 (W12) after treatment. For Whole Exome Sequencing profiling, normal matched skin tissue was available only for the first eight patients.

  Study EGAS00001006736

• Single-cell profiling of neoantigen-specific T cells in lung cancers treated with neoadjuvant PD-1 blockade

  We study the expression profile of MANA-specific T cells, we used the MANA functional expansion of specific T cells (MANAFEST) assay in neoadjuvant anti-PD-1-treated lung cancers and applied their T cell receptor’s (TCR) complementarity-determining region 3 (CDR3) as a “barcode” to track and analyze their transcriptional programs in the tumor microenvironment using single cell TCR sequencing coupled with single cell RNA sequencing. We revealed distinct phenotype for MANA- and virus-specific clones in TIL and adjacent normal lung, regardless of response. MANA-specific T cells show features that drive the differences between responders and non-responders.

  Study EGAS00001005343

• Clinical Outcomes by Tumor Mutational Burden and Inflammatory Gene Expression With Combined Nivolumab and Ipilimumab or Monotherapy in Advanced Melanoma_CM67-RNASeq

  Purpose Exploratory analyses of CheckMate 066 and 067 trials were conducted to investigate associations of tumor mutational burden (TMB), a 4-gene inflammatory gene expression signature, and BRAF mutation status with tumor response, progression-free survival (PFS), and overall survival (OS) in patients with advanced melanoma. Patients and Methods Patients with known programmed death ligand 1 (PD-L1) expression and BRAF mutation status received nivolumab (NIVO) or dacarbazine in CheckMate 066 and either NIVO, ipilimumab (IPI), or NIVO+IPI in CheckMate 067. Whole exome sequencing and RNA sequencing were used to determine TMB and inflammatory gene expression signature scores, respectively. These biomarkers were evaluated in terms of their association with PFS and OS. Results In the NIVO, NIVO+IPI, and IPI arms of CheckMate 067, longer survival was associated with high (> median) versus low (≤ median) TMB with hazard ratios (HRs) (95% confidence interval [CI]) for PFS of 0.45 (0.30–0.65), 0.55 (0.38–0.81), and 0.60 (0.43–0.82), and for OS of 0.46 (0.30–0.71), 0.53 (0.34–0.82), and 0.52 (0.36–0.74), respectively. For NIVO-treated patients, these results were confirmed in CheckMate 066. A survival benefit was observed with high TMB and absence of BRAF mutation. Survival was associated with high versus low inflammatory signature scores with HRs (95% CI) for PFS of 0.56 (0.34–0.94), 0.40 (0.23–0.72), and 0.43 (0.27–0.70), and for OS of 0.37 (0.20–0.66), 0.38 (0.19–0.74), and 0.46 (0.27–0.79), in the NIVO, NIVO+IPI, and IPI arms, respectively. Weak correlations were observed between PD-L1, TMB, and the inflammatory signature. Conclusions Combined assessment of TMB, inflammatory gene expression signature, and BRAF mutation status may be predictive for response to immunotherapy in advanced melanoma.

  Dataset EGAD00001006306

• Dataset for head_and_neck_cancer-RNA

  Rare cancer sequencing data of 92 runs in tumor/control pairs, which were uploaded to umbrella studies. The sequencing was always paired

  Dataset EGAD00001008861

• Dataset for colorectal_cancer-RNA

  Rare cancer sequencing data of 97 runs in tumor/control pairs, which were uploaded to umbrella studies. The sequencing was always paired

  Dataset EGAD00001008855

• QSEA – modelling of genome-wide DNA methylation from sequencing enrichment experiments

  We describe a new method, QSEA, for analyzing methylation enrichment data. We generated a benchmark experiment consisting of MeDIP-seq enrichment data, targeted BS-seq validation data, and RNA-seq data on five pairs of tumor and adjacent normal samples of non-small cell lung cancer patients. Details of the method and its performance on the data have been described in Lienhard et al. (2016).

  Study EGAS00001001822

• Genomic characterisation of SDH deficient renal cell carcinoma - RNA

  SDH deficient renal cell carcinomas are a rare and recently defined subtype of kidney cancer, often associated with an inherited mutation in one of the SDH gene subunits. This dataset sought to understand the genomic events that underpin tumour formation, from putative cell of origin, characterisation of the tumour microenvironment, to the genomic evolution of these rare tumours. We performed whole genome and RNA sequencing of 4 patients with SDH deficient renal cell carcinomas, including one patient who had an additional paraganglioma. An addition patient in this cohort had the initial diagnosis revised to a clear cell renal cell carcinoma.

  Dataset EGAD00001008470

• Single Cell RNA-Sequencing in Adenoid Cystic Carcinoma

  This study of salivary adenoid cystic carcinoma aimed to profile individual malignant and stromal cells in treatment-naive head and neck adenoid cystic carcinoma, with or without metastatic cervical lymph nodes. Clinical and pathologic information was collected on all patients, in addition to a fresh biopsy sample from the primary tumor and/or metastatic lymph node at the time of initial surgery. A fresh biopsy sample from a matched local recurrence was also collected for a single unique patient. Biopsy specimens were processed for single cell RNA-seq. A total of ~1,700 single cells from seven participants were included in the final dataset.

  Study phs003070

• A molecular cell atlas of the human lung from single cell RNA sequencing

  Although single cell RNA sequencing studies have begun providing compendia of cell expression profiles, it has proven more difficult to systematically identify and localize all molecular cell types in individual organs to create a full molecular cell atlas. Here we describe droplet- and plate-based single cell RNA sequencing applied to ~75,000 human lung and blood cells, combined with a multi-pronged cell annotation approach, which have allowed us to define the gene expression profiles and anatomical locations of 58 cell populations in the human lung, including 41 of 45 previously known cell types or subtypes and 14 new ones. This comprehensive molecular atlas elucidates the biochemical functions of lung cell types and the cell-selective transcription factors and optimal markers for making and monitoring them; defines the cell targets of circulating hormones and predicts local signaling interactions including sources and targets of chemokines in immune cell trafficking and expression changes on lung homing; and identifies the cell types directly affected by lung disease genes and respiratory viruses. Comparison to mouse identified 17 molecular types that appear to have been gained or lost during lung evolution and others whose expression profiles have been substantially altered, revealing extensive plasticity of cell types and cell-type-specific gene expression during organ evolution including expression switches between cell types. This atlas provides the molecular foundation for investigating how lung cell identities, functions, and interactions are achieved in development and tissue engineering and altered in disease and evolution.

  Study EGAS00001004344

• Whole exome sequencing and RNA-seq of esophageal squamous cell carcinoma

  We perform integrative genome-wide analyses such as whole-exome sequencing, copy number variant(CNV) analysis, and gene expression analysis using next-generation sequencing and other methods to elucidate driver genes and signaling pathways causing tumorigenesis and cancer progression, leading novel molecular diagnostics and molecular therapies.

  Study JGAS000367

• 1. Identidication of molecular biological mechanism associated with the development and prognosis of uterine cancer, uterine sarcoma, and endometrial hyperplasia / 2. Identification of molecular biological mechanism associated with the development of endometriosis and malignant transformation, ovarian cancer, fallopian tubal cancer, peritoneal cancer, and other malignant tumors in gynecological organs

  To clarify the biological difference between clear cell carcinoma and other histological subtypes in ovarian carcinomas by comparing copy number variants, and to identify molecular subtypes and carcinogenesis in clear cell ovarian carcinomas by whole-exome sequencing and RNA-sequencing. Then, characterize high-grade serous carcinomas by NGS-based, integrative genomic analyses, with focus on homologous recombination deficiency, molecular subtypes, prognostic factors and effectiveness of PARP inhibitor. Based on the results of whole-exome sequencing, an investigator-initiated, phase 2 clinical trial will be conducted to evaluate the efficacy and safety of the PARP inhibitor olaparib in HRD-positive cases.

  Study JGAS000789

• RTEL1 mutation as a modifier of Dyskeratosis Congenita in a family with a Telomerase RNA (hTR) template mutation and variant telomeric repeats

  Vertebrate telomeres, the sequences protecting the end of linear chromosomes, are composed of conserved hexameric GGTTAG repeats. Here we present a C50>A telomerase RNA template mutation that results in the incorporation of the variant telomeric repeat GTTTAG in a family with dyskeratosis congenita primarily presenting as idiopathic pulmonary fibrosis. The mutant telomerase is characterized by decreased processivity in direct telomerase activity assays and in vivo based on data from Illumina next-generation whole genome sequencing and Oxford Nanopore Technologies long-read telomere sequencing. The latter provided positional mutant repeat information that revealed the inheritance and maintenance of proximal mutant repeats in individuals who did not inherit the template mutation. Additionally, we describe an RTEL1 nonsense mutation that is associated with very short telomeres in progeny harboring wild-type telomerase and inherited mutant telomeric repeats in the absence of overt clinical phenotypes. In contrast, co-inheritance of the RTEL1 nonsense and TERC r.C50>A mutations coincided with severe early-onset DC phenotypes in two individuals.

  Study EGAS50000001644

• Single-cell RNA sequencing of bronchoalveolar lavages from COVID-19 patients

  Discriminating mild-moderate from critical COVID-19 disease by innate and adaptive immune single-cell profiling of bronchoalveolar lavages.

  Study EGAS00001004717