14982 results for "cancer studies using rna-seq"

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• Single-cell profiling reveals monocyte mitochondrial dysfunction in patients with cirrhosis progressing to acute-on-chronic liver failure

  We performed single-cell RNA-seq and CITE-seq in PBMC samples derived from patients with acutely decompensated cirrhosis at risk of developing ACLF, as well as from Healthy Donors. We identified a population of monocytes associated with disease progression. We also explored the presence of this cell population in blood samples by bulk RNA-sequencing.

  Study EGAS50000001127

• Single-cell RNA-seq of immune cells from Melanoma tumors (Li et al, 2018)

  Single-cell RNA-seq profiling of immune cells sorted from human Melanoma tumors (and several matching PBMC samples). Contains de-multiplexed FASTQ files per plate (MARS-seq amplification batch, total 204 samples) and also de-multiplexed FASTQ files of single-cell TCRb-seq.

  Dataset EGAD00001004497

• A phase II trial of the aurora kinase A inhibitor alisertib for patients with castration resistant and neuroendocrine prostate cancer: efficacy and biomarker evaluation

  Neuroendocrine prostate cancer (NEPC) is an aggressive variant of prostate cancer that may develop de novo or as a mechanism of treatment resistance. N-myc is capable of driving NEPC progression. Alisertib inhibits the interaction between N-myc and its stabilizing factor Aurora-A, inhibiting N-myc signaling, and suppressing tumor growth. In this single arm, multi-institutional open label phase 2 clinical trial of alisertib, sixty men were treated with alisertib 50mg twice daily for 7 days every 21-days. Eligibility included metastatic prostate cancer and at least one: small cell neuroendocrine morphology; ≥50% neuroendocrine marker expression; new liver metastases without PSA progression; elevated serum neuroendocrine markers. The primary endpoint was six-month radiographic progression free survival. Pre-treatment biopsies were evaluated by whole exome and RNA-seq.

  Study phs001666

• Genomics and Epigenomics of the Elderly Response to Pneumococcal Vaccines

  Pneumococcal Vaccine Study: This is a study designed to develop a detailed transcriptional and cellular profile of the immune response to pneumococcal vaccination with conjugated and non-conjugated polysaccharide vaccines in the senescent immune system of older adults. In this study, 39 healthy adults ages 60 and older that have never received pneumococcal vaccination, have been randomized to receive Prevnar 13 (Pfizer), a conjugated 13-valent vaccine or Pneumovax 23 (Merck), a non-conjugated 23-valent vaccine. Four (4) study visits occurred over 70 days at Day -7 (baseline), day 1, day 10 and day 60 (± 5d) post vaccination.Bulk RNA-sequencing data are available on the 4 time points for 31 of the participants and 1 replicate. ATAC-Doublet Detector Study: We generated single nucleus ATAC-seq (snATAC-seq) data from PBMCs of 2 baseline blood samples from the pneumococcal study. Generated data was then used to benchmark a novel computational method for detecting multiplets in snATAC-seq data, namely, AMULET (https://github.com/UcarLab/AMULET). Multiplets confound downstream analyses by introducing combined epigenomic profiles from 2 or more cells/nuclei. AMULET detects multiplets by using unique snATAC-seq data features that allow it to reliably use read counts to detect multiplets for their removal from data analyses.

  Study phs002361

• Single-cell RNA-seq cases

  Single-cell RNA-seq cases (Tumor and adjacent tissue)

  Dataset EGAD00001008835

• Whole blood RNAseq from a large ALS case-control study at Univ of Michigan

  This dataset consists of 694 bulk RNA-seq data (sorted aligned BAM files) from whole blood of ALS participants meeting the Gold Coast definition of ALS during their clinical visit (n=422) and healthy controls (n=272) at the University of Michigan (UM). Samples were collected as part of the UM Pranger ALS Clinic between 2011-2021, and prepared either using poly-A selection of rRNA depletion (see Experiments). RNAseq was performed on the NovSeq 6000 S4 at the UM Advanced Genomics Core, resulting in 150bp paired-end reads. Raw reads were trimmed using Cutadapt (v2.3) and aligned to hg38 using STAR (v2.5.3a). Age provided is the age at blood sample collection date.

  Dataset EGAD50000001488

• MP2PRT: Genomic and Molecular Characterization of Biomarkers Associated with Tumor Angiogenesis, DNA Repair, and Immunologic Tolerance using Samples from the NRG Oncology Phase 3 Randomized Trial, GOG-0240 (NCT00803062)

  The Molecular Profiling to Predict Response to Treatment (MP2PRT) program is part of the NCI's Cancer Moonshot Initiative. The aim of this program is the retrospective characterization and analysis of biospecimens collected from completed NCI-sponsored trials of the National Clinical Trials Network and the NCI Community Oncology Research Program. This study is one of the selected studies under this program. For this study, genomic characterization (WGS, WXS, Total RNAseq, miRNAseq) has been performed on cervical tumor tissue from patients with advanced disease (persistent, recurrent, and metastatic) and matching germline samples. It is hypothesized that the characterization of these tissues using next generation sequencing will lead to the identification of relevant novel genetic aberrations within the immunologic, DNA repair, and tumor angiogenesis domains that dichotomize the study population into exceptional responders and non-responders to systemic therapy, with a spectrum of response manifesting between the two extremes.

  Study phs002293

• Dissecting Cell Composition and Drug Sensitivity in Human Adenoid Cystic Carcinomas (ACCs)

  The study reports the results of single-cell RNA sequencing (scRNA-seq), RNA sequencing (RNA-seq), and whole-exome sequencing (WES) experiments performed on malignant cells isolated by flow cytometry from seven patient-derived xenograft (PDX) lines established from human Adenoid Cystic Carcinomas (ACCs). Of these seven lines, five are characterized by well differentiated histology (ACCX5M1, ACCX6, ACCX14, ACCX22, SGTX6) and two by solid histology (ACCX9, ACCX11). Analysis by scRNA-seq of the well-differentiated PDX line ACCX22 led to identification of cell-surface markers (CD49f, KIT) that enabled the differential purification of the two major cellular components contained in well-differentiated ACCs: myoepithelial-like (CD49f-high/KIT-negative) and ductal-like (CD49f-low/KIT-positive) cells. The study reports the analysis by RNA-seq and WES of purified preparations of myoepithelial-like and ductal-like cells from well-differentiated PDX lines (ACCX5M1, ACCX6, ACCX14, ACCX22, SGTX6) and of ductal-like (CD49f-low/KIT-positive) cells from solid PDX lines (ACCX9, ACCX11).

  Study phs002764

• 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

• Lactobacillus rhamnosus GG ATCC (LGG) as an immune adjuvant for influenza vaccination in the elderly

  Double blind Randomized Controlled trial to evaluate the safety of Lactobacillus rhamnosus GG ATCC 53103 (LGG) vs placebo in elderly receiving Trivalent Inactivated Influenza Vaccine (TIV) (study 1) or Double blind Randomized Controlled trial to evaluate the safety of Lactobacillus rhamnosus GG ATCC 53103 (LGG) vs. placebo in elderly subjects receiving Live Attenuated Influenza vaccine (LAIV) (study 2). Healthy elderly volunteers, ages 65-80 were enrolled as outpatients in two clinical studies in which they received the TIV vaccine (study 1, n=28) or the LAIV vaccine (study 2, n=30). In each of the 2 studies, subjects were randomized to receive either LGG capsules containing 1 x 1010 CFU, twice daily for 28 days, or matching placebo capsules twice daily for the same period of time. The study subjects completed a daily diary, telephone calls, and study visits at the Massachusetts General Hospital Clinical Research Centers at baseline, days 21, 28 and 56 and month 5 for the TIV study and baseline, days 21, 28, and 56 for the LAIV study. During each visit, the subject diary, interim history, potential adverse effects and concomitant medications were reviewed and vital signs and a physical examination were performed. Routine blood tests were obtained to monitor for safety during visits and nasopharyngeal and stool samples were collected for microbiome analysis. Volunteers in both studies who were interested in participating in the effect of LGG probiotic on the Human whole Blood Transcriptome substudy also had blood drawn for DNA and RNA extraction, after signing the substudy consent form. The main objectives of the TIV and LAIV studies were to assess the safety and tolerability of 2 x 1010 CFU LGG administered orally to elderly subjects for 28 days after administration of TIV (study 1) or LAIV (study 2). Secondary objectives were to evaluate the richness and microbial diversity in nasopharyngeal and stool specimens using pyrosequencing, and to compare cytokine production in response to bacterial stimulation by following the kinetics of mRNA expression of pro and anti-inflammatory genes and different signaling pathways, in relation to changes in stool Bifidobacterium and Lactobacillus spp. The studies were reviewed and approved by the Partners Human Research Committee (TIV study IRB # 2010p001694 and LAIV study IRB # 2011p002849) and were registered at ClinicalTrials.gov (NCT01368029 and NCT01545349, respectively).

  Study phs000981

• Adeno-associated virus in the liver: natural history and consequences in tumor development

  Adeno-associated virus (AAV) is a defective mono-stranded DNA virus, endemic in human population (40-80%). AAV infection has long been considered as non-pathogenic1, however few years ago we reported for the first time recurrent clonal AAV2 insertion in the pathogenesis of human hepatocellular carcinoma (HCC) developed on normal liver. These clonal viral insertions target cancer driver genes, including CCNA2, CCNE1, TERT, TNFSF10 and MLL4, leading to their overexpression. The viral inserted sequences involved in almost all the cases the 3’ inverse tandem repeat (ITR) of AAV2, which is important for virus integration in host DNA and exhibits a promoter/enhancer activity. Here, we used RNA sequencing (RNA-seq) to investigate their functional impact on the tissue, such as fusion transcript generation events.

  Study EGAS00001003310

• RNA-Seq of chronic lymphocytic leukemia

  398 runs and 184 samples of CLL paired RNA-Seq. Sequences were prepared with the Illumina TruSeq RNA Kit. Paired sequencing was done on Hiseq2000 or Hiseq2500.

  Dataset EGAD00001009637

• NKI-AvL OpACIN RNA-seq of stage III melanoma patients

  The dataset “NKI-AvL OpACIN RNA-seq of stage III melanoma patients" includes 18 FASTQ files from single-end total RNA sequencing on Illumina HiSeq2500 for 18 stage III melanoma patients.

  Dataset EGAD00001004216

• Probabilistic modeling of personalized drug combinations from integrated chemical screen and molecular data in sarcoma

  Background: Cancer patients with advanced disease exhaust available clinical regimens and lack actionable genomic medicine results, leaving a large patient population without effective treatments options when their disease inevitably progresses. To address the unmet clinical need for evidence-based therapy assignment when standard clinical approaches have failed, we have developed a probabilistic computational modeling approach which integrates sequencing data with functional assay data to develop patient-specific combination cancer treatments. Methods: Tissue taken from a murine model of alveolar rhabdomyosarcoma was used to perform single agent drug screening and DNA/RNA sequencing experiments; results integrated via our computational modeling approach identified a synergistic personalized two-drug combination. Cells derived from the tumor were allografted into mouse models and used to validate the personalized two-drug combination. Computational modeling of single agent drug screening and RNA sequencing of multiple heterogenous sites from a single patient’s epithelioid sarcoma identified a personalized two-drug combination effective across all tumor regions. The heterogeneity-consensus combination was validated in a xenograft model derived from the patient’s primary tumor. Cell cultures derived from human and canine undifferentiated pleomorphic sarcoma were assayed by drug screen; computational modeling identified a resistance-abrogating two-drug combination common to both cell cultures. This combination was validated in vitro via a cell regrowth assay. Results Our computational modeling approach addresses three major challenges in personalized cancer therapy: synergistic drug combination predictions (validated in vitro and in vivo in a genetically engineered murine cancer model), identification of unifying therapeutic targets to overcome intra-tumor heterogeneity (validated in vivo in a human cancer xenograft), and mitigation of cancer cell resistance and rewiring mechanisms (validated in vitro in a human and canine cancer model). Conclusions These proof-of-concept studies support the use of an integrative functional approach to personalized combination therapy prediction for the population of high-risk cancer patients lacking viable clinical options and without actionable DNA sequencing-based therapy.

  Study EGAS00001003564