11934 results for "cancer rna-seq"

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• Juvenile Sjogren's Syndrome (JSS) Transcriptome Study

  Sjögren's disease (SjD) is a systemic autoimmune disorder with major clinical manifestations of dryness in the eyes and mouth, fatigue, and joint pain. Our interdisciplinary experts in SjD at the University of Florida newly discovered and established a cohort of SjD in children. Many of these patients with childhood SjD (cSjD) demonstrated a prominent feature of recurrent parotitis (RP). To understand the immunopathogenesis of childhood SjD (cSjD) for the first time in the field, we profiled the transcriptome of five groups of four PBMC samples by unbiased, high-throughput single-cell RNA sequencing (scRNA-seq): cSjD (n=4), non-cSjD (n=4), biopsy-positive non-cSjD (BP, n=4), biopsy-positive non-cSjD with RP (BPRP, n=4), and healthy controls (HC, n=4). In this study, RNA sequencing data, as well as all barcodes.tsv.gz, features.tsv.gz, and matrix.mtx.gz that may be used to create a Seurat object in R, will be availableTo protect the confidentiality of subjects, certain data were not assessed or collected in the subject phenotype dataset, such as race, age, height, weight, and education.

  Study phs003048

• DLBCL NGS Genomic Datasets of non-China cohort from Phoenix Clinical Trial

  Study biopsies (n=773; 189 cases as China cohort and 584 cases as non-China cohort) underwent whole exome sequencing or targeted gene panel DNA sequencing and RNA sequencing, allowing the identification of somatic mutations. Tumors were assigned to DLBCL genetic subtypes as the MCD (n=110), BN2 (n=47) or N1 (n=28) using the LymphGen algorithm based on their somatically mutated genes. In younger patients (age≤60), ibrutinib plus R-CHOP was associated with a 100% event free survival (EFS) at 3-years in the MCD and N1 groups, whereas R-CHOP alone was associated with a 3-year EFS of 42.9% (p=0.01) and 50% (p=0.016) in the MCD and N1 groups, respectively. This analysis showed a benefit of ibrutinib with R-CHOP chemotherapy in particular genetic subtypes, providing mechanistic support for its survival benefit in younger patients with non-GCB DLBCL. The EGA collects RNA-Seq and NuGene targeted sequencing datasets of 584 cases for non-China cohort.

  Study EGAS00001005554

• A Phase II Study: CRS207/GVAX Plus Anti-PD1 and Anti-CTLA4 Recruits Mesothelin- and KRAS-Specific T cells into PDAC

  This study examined immunologic correlatives from a phase II study evaluating CRS207/GVAX vaccines in combination with anti-PD1 and anti-CTLA4 in metastatic pancreatic cancer (NCT03190265). Arm A received CRS207/GVAX with anti-PD1 and anti-CTLA4 therapy; Arm B received CRS207 with anti-PD1 and anti-CTLA4 therapy. Patients undergoing treatment in this trial had peripheral blood mononuclear cells (PBMCs) and tumor tissue biopsied serially at pre-treatment and on-treatment timepoints. Single-cell RNA/TCR sequencing was employed on PBMCs. Bulk RNA/TCR sequencing was employed on tumor tissues. We identified treatment-enriched inflammatory pathways as well as T cell repertoires.

  Study phs003798

• TCR- and BCR-sequencing data for The interface of malignant and immunologic clonal dynamics in high-grade serous ovarian cancer

  Each tumor sample was cut into three pieces, yielding two end-pieces for cryovials and a middle portion placed in 10% buffered formalin. End pieces were homogenized manually and with a paddle blender (Stomacher). All paraffin-embedded blocks, including formalin-fixed tumor samples and molecular-fixed fallopian tubes, were sectioned and stained with hematoxylin and eosin prior to expert histopathological review to confirm the presence of high grade serous carcinoma. Homogenized end pieces were then flash frozen, and RNA was extracted using the miRNeasy Mini kit. Nanodrop was used to assess quality (260/280) and quantity. Total RNA samples were also QC checked using the Caliper HT RNA HiSens assay. Samples ranging from 60-255ng RNA were re-arrayed into a 96-well plate. 5'-RACE PCR was carried out as described in "The interface of malignant and immunologic clonal dynamics in high-grade serous ovarian cancer" (Zhang et al.). Briefly, this involved first round and nested PCR with TRB (TCR beta chain) and IGH (immunoglobulin heavy chain) gene-specific primers. The indexed libraries were sequenced on the Illumina HiSeq platform with paired-end 250bp reads using v2 chemistry reagents.

  Dataset EGAD00001003985

• Inhibition of CDK4/6 Promotes CD8 T Cell Memory

  Inhibitors of Cyclin-Dependent Kinase 4 and 6 (CDK4/6) have been recently deployed for the treatment of advanced breast cancer. Despite their success, the mechanism of action of these drugs is unclear. In mice, treatment with a CDK4/6 inhibitor improve T cell memory responses and protect mice against tumor rechallenge. We aimed to identify the correlates of this finding in human subjects. In this study, blood was collected from 5 breast cancer patients before and during treatment with the CDK4/6 inhibitors abemaciclib or palbociclib. Blood was also collected from 2 breast cancer patients who did not receive a CDK4/6 inhibitor. Recently activated CD8 T cells (CD45RO+ CD45RA+) were sorted and subjected to single-cell RNA sequencing.

  Study phs002448

• Temporal Evolution Reveals Bifurcated Lineages in Aggressive Neuroendocrine Small Cell Prostate Cancer Trans-Differentiation

  Trans-differentiation from adenocarcinoma to small cell neuroendocrine (SCN) cancer is an adverse consequence of treatment escape in various cancers, including prostate, lung, and bladder cancers (Balanis and Sheu et al., PMID 31287989). Expression of dominant negative p53 (TP53DN), myrAkt1, RB1-shRNA, c-Myc, and Bcl2(PARCB forward transformation) using human naïve prostate basal epithelial cells recapitulated both transcriptional and histological characteristics of small cell neuroendocrine prostate cancer (NEPC) (Park et al., PMID 30287662). To study the temporal transcriptional landscape during this trans-differentiation process, we conducted a time course study using a PARCB model by integrating multi-omics sequencing, including bulk RNA-sequencing and ATAC-sequencing on samples taken at different time point, as well as single cell RNA sequencing on serial xenograft tumors. We found a common SCN pathway that resulted in two distinct end states defined by mutually exclusive expression of ASCL1 and ASCL2. Further investigation using CUT&RUN sequencing identified TFAP4 as a potential epigenetic regulator of both proteins. Our study reveals temporal and transcriptional changes from prostate adenocarcinoma to NEPC trans-differentiation.

  Study phs003230

• Hypermutation of the inactive X chromosome is a frequent event in cancer

  Mutation is a fundamental process in tumorigenesis. However the degree to which the rate of somatic mutation varies across the human genome and the mechanistic basis underlying this variation remain to be fully elucidated. As part of the ICGC PedBrain and Malignant Lymphoma (MMML-Seq) consortium we performed a cross-cancer comparison of whole genomes comprising a diverse set of childhood and adult tumors including both solid and hematopoietic malignancies. In addition we performed whole genome sequencing of clonally expanded hematopoietic stem/progenitor cells (HSPCs) from healthy individuals to compare somatic mutation rates.

  Study EGAS00001000565

• Gene expression profiles of single disseminated breast cancer cells

  A set of 56 EpCAM-positive cells derived from bone marrow aspirates of breast cancer patients or patients without a cancererous disease (30 cells from 21 M0-stage and 11 cells from five M1-stage breast cancer patients, 15 cells from seven non-cancer patients serving as controls). EpCAM-positive cells from breast cancer patients were considered disseminated tumor cells as they harbored copy number alterations and showed high expression of the epithelial marker EpCAM and the mammary luminal progenitor marker KIT in comparison to EpCAM-positive bone marrow cells from non-cancer patients. Paired-end RNA-Sequencing of the samples was performed on Illumina NovaSeq6000, raw data are provided in the Fastq format.

  Dataset EGAD00001006359

• Unraveling the transcriptomic profile of utero-tubal lavage fluid of ovarian cancer patients

  The majority of ovarian cancers are diagnosed at an advanced stage and have a high mortality rate. Current screening strategies fail to improve prognosis because markers of early stage disease are lacking. This medical need justifies the search for biomarkers enabling early detection of ovarian cancer. In this study, we explore the extracellular transcriptome of utero-tubal lavage fluid obtained from 26 ovarian cancer patients and 48 controls using messenger RNA (mRNA) capture and small RNA sequencing. Because of its contact with the fallopian tube and the ovaries, collection of utero-tubal lavage might be the preferred non-invasive method to identify localized lesions compared with analyses based on peripheral blood samples. We observed an enrichment of ovarian and fallopian tube specific messenger RNAs in utero-tubal lavage fluid compared to other human biofluids. Over 300 mRNAs and 41 miRNAs were upregulated in ovarian cancer samples compared with controls. Upregulated genes were enriched for genes involved in cell cycle activation and proliferation, hinting at a tumor derived signal. In conclusion, we provide proof-of-principle that mRNA capture sequencing of utero-tubal lavage fluid is technically feasible, and that the extracellular transcriptome of utero-tubal lavage should be further explored in larger cohorts to assess the diagnostic value of the biomarkers identified in this study.

  Study EGAS00001005498

• untargeted whole genome sequencing - Evaluation and correction of GC biases in cell-free DNA at the fragment level

  These are aligned paired-end reads from Illumina NovaSeq 6000 whole-genome sequencing of 4 cfDNA samples extracted from blood plasma (plasma-Seq). Three samples from patients with breast cancer, prostate cancer, or colorectal cancer and one sample from a healthy individual were aligned to GRCh38 (GCA_000001405.15_GRCh38_no_alt_plus_hs38d1_analysis_set). The observed GC bias is different in each of these cfDNA samples which leads to different average GC content per sample. This bias is corrected using the GCparagon commandline tool.

  Dataset EGAD00001010100

• Single-cell RNA sequencing of human IL-18R supported CAR T cells targeting oncofetal Tenascin C

  C.TNC-CAR.Zip18R CAR-T cells are from 2 donors and multiplexed 10x Genomics scRNA-seq were performed with a hashtag to label each sample. For tumor and CAR-T cell cocluture samples, CAR-T cells were extracted from 3 time points. The raw data are fastq format for total 20 samples considering sequencing lanes. The multiplexing information, CAR and Zip18R sequences are deposited in analyses.

  Study EGAS50000000772

• Hashed data from three immortalized fibroblastic reticular cells (iFRCs)

  Co-culture experiments of primary lymphoid and DLBCL-derived immortalized FRCs (iFRC) followed by scRNA-seq. iFRCs as well as lymphocytes from DLBCL samples (n=3) were harvested after 24h of incubation and different experimental conditions were multiplexed using in-house cell multiplexing oligonucleotides (CMOs; full list of barcodes provided in Table S9). Cells were incubated with CMOs at a final concentration of 1.8 μM for 20 minutes on ice, followed by four washes with PBS (centrifugation at 400 × g for 3 minutes at 4 °C). Single-cell RNA sequencing (scRNA-seq) and multiplexing libraries were prepared using the 10x Genomics Single Cell 3′ Gene Expression v4 assay, according to the manufacturer’s protocol. Sequencing was performed on an Illumina NovaSeq 6000 platform using paired-end 100 bp reads on an S4 flow cell.

  Dataset EGAD50000001779

• Cryptic Splice Mutation in the Fumarate Hydratase Gene in Patients With Clinical Manifestations of Hereditary Leiomyomatosis and Renal Cell Cancer (HLRCC)

  Four patients with hysterectomy were evaluated for biochemical and molecular evidence of autosomal dominant Fumarate Hydratase (FH) alterations causing Hereditary Leiomyomatosis and Renal Cell Cancer (HLRCC). HLRCC is an autosomal dominant condition characterized by the development of cutaneous and uterine leiomyomas, and risk for development of an aggressive form of papillary renal cell cancer. Enzyme assay, western blot analyses, direct nanopore RNA sequencing, and whole genome sequencing (WGS) were utilized. The study identified a cryptic splice mutation in intron 9 of the FH gene that results in retention of 57 base pairs of intronic sequence in the affected allele of the mature FH mRNA.

  Study phs003381

• RNA-seq of Glioblastoma stem cells

  Chromatin accessibility discriminates stem from mature cell populations, enabling the identification of primitive stem-like cells in primary tumors, such as Glioblastoma (GBM) where self-renewing cells driving cancer progression and recurrence are prime targets for therapeutic intervention. We show, using single-cell chromatin accessibility, that primary GBMs harbor a heterogeneous self-renewing population whose diversity is captured in patient-derived glioblastoma stem cells (GSCs). In depth characterization of chromatin accessibility in GSCs identifies three GSC states: Reactive, Constructive, and Invasive, each governed by uniquely essential transcription factors and present within GBMs in varying proportions. Orthotopic xenografts reveal that GSC states associate with survival, and identify an invasive GSC signature predictive of low patient survival. Our chromatin-driven characterization of GSC states improves prognostic precision and identifies dependencies to guide combination therapies.

  Study EGAS00001003070

• Assessment of RNA-Seq Sample Preparation Methodology

  The goal of this study was two-fold, to determine if common purification techniques have any effect on downstream differential expression analysis and to evaluate combinations of alignment and differential expression software for reliability. To this end, blood was collected from three individuals and pooled during and after extraction. After pooling and mixing was completed, samples were divided into three aliquots for testing. The first aliquot was a control and not purified or concentrated. It was diluted to produce samples of varying concentrations for testing. The second aliquot was diluted to 20 ng/μL and used to test six different variations on the AMPure XP bead purification procedure. The last aliquot was also diluted to varying concentrations of 60, 30, and 9.6 ng/μL and purified using MinElute columns. Samples were submitted for total RNA-Seq library preparation and sequencing. Library preparation was performed using the TruSeq Stranded Total RNA with Ribo-Zero Globin kit (20020612, Illumina Inc.), and 2x150 bp PE sequencing was done on an Illumina NovaSeq 6000 with the S4 reagent kit. Comparisons were made between methods (AMPure vs. unpurified, AMPure vs. MinElute, MinElute vs. unpurified) to assess the effects of purification method on downstream differential expression. Comparisons were also made within methods using the varying concentrations tested for unpurified samples and for MinElute purified samples to assess the effects of concentration on differential expression. Variations of the AMPure procedure were also compared to assess the effectiveness of the variations tested in comparison to the unmodified procedure. A subset of samples was selected for use with alignment and differential expression package comparison. Unpurified high concentration samples eluted in RNAse-free water were compared to unpurified high concentration samples eluted in BR5, a buffer from the PAXgene blood miRNA kit, with the expectation that there should be no or very few differentially expressed genes. Unpurified high concentration samples eluted in RNAse-free water were also compared to unpurified low concentration samples also eluted in RNAse-free water, with possibly a small number of differentially expressed genes anticipated. A third dataset of simulated RNA-seq data was created with a known rate of differential expression. These files were aligned using Bowtie2, HISAT2, kallisto, RSEM, Rsubread, Salmon, and STAR. Results were then analyzed for differential expression using ALDEx2, baySeq, DEGseq, DESeq2, edgeR, limma, NOISeq, PoissonSeq, and SAMseq. Differential expression results of all three comparisons were evaluated to determine which combinations provided the most reliable results for both real and simulated data.

  Study phs003001

• Single-cell transcriptomic analyses of peritoneal metastases from patients with colorectal cancer metastasized to the peritoneum

  The data published here contains single-cell RNA-sequencing (scRNAseq) data as obtained using the 3' scRNAseq using Chromium Single Cell 3’ Reagent from 10X Genomics on peritoneal metastases (PM) from patients with colorectal cancer (CRC) and PM. Sequencing was performed in a paired-ended fashion on the NovaSeq6000.

  Dataset EGAD50000000249

• RNA Sequencing of Colorectal Liver Metastases

  A subset of patients with metastatic colorectal cancer achieves prolonged survival after hepatic resection of limited liver metastases. Here, we examined the molecular features of colorectal liver metastases as they relate to clinical outcomes.

  Study EGAS00001002945

• Long-read-transcriptome-sequencing of CLL and MDS patients uncovers common molecular effects of SF3B1 mutations

  Mutations in SF3B1 occur frequently in patients with chronic lymphocytic leukemia (CLL) and myelodysplastic syndromes (MDS), and a full-length transcriptome approach can expand our current knowledge on SF3B1 mutation effects on RNA splicing. We applied long-read-transcriptome-sequencing (LRTS) to 44 MDS and CLL patients with and without SF3B1 mutations and found a large fraction (>60%) of novel isoforms. Furthermore, we revealed that mutation effects on alternative splicing were largely common in both cancer types and specifically altered the usage of introns as well as 3’-splice-sites. We combined the LRTS with genome-wide SF3B1-RNA binding maps and show multimodal binding at 3’-splice-sites highlighting a window of 12-21nt upstream of the canonical 3’-splice-site in which a dynamic switch in splice site usage is observable in patients carrying SF3B1 mutations. Our work presents the hitherto most complete LRTS study in CLL and MDS and provides a resource for further research on aberrant splicing in cancer.

  Study EGAS50000000053

• Infiltrative and drug-resistant slow-cycling cells support metabolic heterogeneity in glioblastoma

  Glioblastoma patient derived Fast/Slow cycling cancer stem cell RNA sequencing. Consists of 3 patient cell lines and 6 files

  Dataset EGAD00001004380

• Gastrointestinal Cancer Treatment Responders

  Comprehensive genomic profiling of colon adenocarcinomas has revealed multiple recurrent alterations that may inform new treatment strategies. Clinical trials of these agents are ongoing, although the mechanisms of response and resistance to these agents are not well characterized. The goal of this study is to perform comprehensive profiling of pre-treatment and post-resistance tumor and germline samples obtained from patients with colon cancer who receive these agents by carrying out whole exome sequencing and RNA sequencing, and to use these data to identify mechanisms of response and resistance.

  Study phs000803

• Acquired Cross-Resistance in Small Cell Lung Cancer Patient-Derived Xenografts

  Here we present whole genome sequencing and RNA sequencing of patient-derived xenograft (PDX) models of small cell lung cancer (SCLC). These models were derived at a variety of clinical time points from either biopsy/resection samples, malignant effusions, or circulating tumor cells (CTCs), and grown in the subcutaneous flank of NSG (NOD.Cg-Prkdcscid Il2rgtm1Wjl /SzJ) mice. The first analysis published with these data was to determine the genomic and transcriptomic features of PDX models derived after relapse that demonstrated in vivo resistance to multiple chemotherapy regimens (cross-resistance).

  Study phs003486

• Genetic drivers of epigenetic and transcriptional variation of human immune responses to infection (RNA-seq, ATAC-seq and ChIPmentation)

  RNA-seq, ATAC-seq and ChIPmentation data from monocyte-derived macrophages that were infected with Influenza A virus strain PR8WT, or a matching non-infected control.

  Dataset EGAD00001008422

• Comprehensive molecular and clinicopathological profiling of lung adenocarcinoma in Japanese never or light smokers

  Studies have yet to characterize the differences in molecular profiles of lung adenocarcinoma (LUAD) among divergent ethnic groups. Herein, we conducted comprehensive molecular profiling of LUAD in never or light smokers from Asia in order to discover novel targetable mutations and prognostic biomarkers of this distinct disease entity. Methods: We analyzed 996 cases of Asian LUAD, and performed whole-exome sequencing and/or RNA-seq in 125 cases of Asian LUAD negative for the driver oncogenes defined by conventional laboratory testing. We also investigated the clinical and pathological characteristics among the 996 cases. Results: Driver oncogenes were identified in 88 cases (70.4%) with specific hotspot mutations differing from those in The Cancer Genome Atlas (TCGA) study. Clustering based on mRNA expression profiles, but not genetic mutational ones, could predict patient prognosis. The risk score generated by the expression of a three-gene set was a strong prognostic marker for overall survival and progression-free survival in our cohort, and was further validated using TCGA cohort. Among the 996 cases, each driver alteration is distributed across all histological subtypes. Adenocarcinoma in situ was identified to harbor driver mutations, suggesting that these alterations are early events in the pathogenesis of LUAD. This study indicates the value of applying gene expression profiling for predicting the prognosis after a surgical operation, and that the identification of actionable mutations is important for optimizing targeted drugs in Japanese LUAD.

  Study JGAS000215

• Tumor gene expression profiles for the study "TGF-β attenuates tumour response to PD-L1 blockade by contributing to exclusion of T cells"

  RNA was extracted from formalin-fixed and paraffin embedded tumors of a large cohort of bladder cancer patients before treatment with anti-PD-L1. RNA was sequenced using a capture based approach (exome capture, RNA access).

  Dataset EGAD00001003977

• A Phase I Study With a Personalized Neoantigen Cancer Vaccine in Glioblastoma Multiforme

  Neoantigens, which are derived from tumor-specific protein-coding gene mutations, are exempt from central tolerance, can generate robust immune responses and function as bona fide antigens that facilitate tumor rejection. A strategy of using multi-epitope and personalized neoantigen vaccination has previously been tested in patients with high-risk melanoma. We demonstrated that this strategy is feasible for glioblastoma (GBM) which typically has a relatively low mutation load and an immunologically 'cold' tumor microenvironment. We conducted whole exome sequencing (WES) of tumor and normal cells from individual GBM patients to identify tumor-specific mutations. We assessed the expression of mutated alleles by RNA-sequencing of tumor, and used personalized neoantigen-targeting vaccines to immunize newly diagnosed GBM patients following surgical resection and conventional radiotherapy in a phase I/Ib study. Patients who did not receive dexamethasone, a highly potent corticosteroid that is frequently prescribed to treat cerebral oedema in GBM patients, generated circulating polyfunctional neoantigen-specific CD4+ and CD8+ T cell responses that were enriched in a memory phenotype and showed an increase in the number of tumor-infiltrating T cells. Using single-cell T cell receptor analysis, we provided an evidence that neoantigen-specific T cells from the peripheral blood can migrate into an intracranial GBM tumor. Neoantigen-targeting vaccines thus have the potential to favorably alter the immune environment of GBM.In order to discover cancer antigens derived from annotated and unannotated protein-coding regions of the genome, we carried out matched ribosome profiling (Ribo-Seq) on two GBM samples. We discovered novel or unannotated open reading frames (nuORFs) and their expression levels as well as somatic mutations within the nuORFs, which could be used to predict potential neoantigens.

  Study phs001519