3883 results for "RNA AND sequencing OR transcriptome"

in 34.93 milliseconds.

• Acral Melanoma PDXs from the admixed Brazilian Population- Human RNA expression data from Patient Derived Xenograft samples - htseq count files

  Files containing the read counts obtained with obtained with HTSeq for all the genes in Ensembl v103 annotation for GRCh38 human reference genome. This dataset contains the files for all the Patient Derived Xenograft samples. Counting was performed using filtered BAM files after the removal of mouse reads with XenofilteR. Acral melanoma (AM) is an aggressive melanoma subtype with limited therapeutic options and poor outcomes. In non-European descent and admixed populations, like in Latin America, it can account for a significant proportion of cutaneous melanoma cases. Here, we performed comprehensive genomic and functional profiling of AM from a uniquely diverse Brazilian cohort. Whole-exome and transcriptome sequencing was performed on both tumours and patient-derived xenograft (PDX) samples. The PDX were obtained from a comprehensive collection of patient-derived xenograft (AM-PDX) models that we established which faithfully retained the histopathological and genomic features of the original tumours.

  Dataset EGAD00001015747

• Transcriptomic Profiling of Bulk Tissue and Laser-Capture Microdissected Neurons of Postmortem Human Brains in the Superior Temporal Gyrus

  We performed RNA-Seq on bulk tissue and laser-capture microdissected (LCM) neurons from 59 postmortem human brains in the superior temporal gyrus (STG) to investigate Autism Spectrum Disorder (ASD)-associated transcriptomic changes. We examined post-mortem brain tissue from 27 subjects with ASD and 32 neuro-typical controls. Raw RNA-Seq data in FASTQ format are provided.

  Study phs003208

• CMML Collection of WES, WGS, RNA-Seq and ERRBS data

  We first performed a comprehensive analysis of the genome of 66 chronic myelomonocytic leukemia cases using whole exome (N=49) or whole genome (N=17) sequencing for paired leukemic-control DNA. Then, we realized serial analysis of whole exome sequence in 17 cases, completed with serial RNA sequencing and DNA methylation analysis in 9 cases, including patients treated or not with hypomethylating agents.

  Study EGAS00001001264

• Surveillance, Epidemiology and End Results (SEER) Formalin Fixed Paraffin Embedded (FFPE) Tissue Feasibility Study

  Next Generation Sequencing (NGS) technologies are being used for detection of somatic mutations in tumors and studies of germline variation. However, most NGS studies used DNA isolated either from whole blood or fresh frozen tissue specimens. Meanwhile, the tissue specimens available from most National Cancer Institute (NCI) funded cohorts and the Surveillance, Epidemiology and End Results (SEER) registries (http://seer.cancer.gov/biospecimen) are primarily formalin fixed paraffin embedded (FFPE). There are limited data, on a small number of FFPE tissue samples, which suggest NGS is feasible. Much less is known about the feasibility of these technologies for large scale studies or using older FFPE specimens (e.g. 5-30 years old). The SEER cancer registries cover approximately 28% of the United States population, providing high quality demographic, clinical, pathologic, and survival data. The SEER Residual Tissue Repository (RTR) program was established in 2003. The RTR maintains biospecimens obtained from three of SEER' population-based cancer registries: Iowa, Hawaii, and Los Angeles. Investigators at government, academic, and nonprofit institutions may apply to the program to obtain annotated FFPE tumor tissue specimens to study biomarkers, etiology, and other aspects with a population-based sample of cancer cases. The main objective of this project was to conduct a pilot study to determine whether the DNA obtained from archival FFPE tissue from 3 SEER Registries is of sufficient quality and quantity to conduct NGS. For Exome sequencing, sixty high-grade serous ovarian adenocarcinomas from FFPE tissues which were between 7 and 31 years old were obtained from three SEER registries. DNA was extracted, quantified, quality assessed, and subjected to whole exome sequencing. DNA extraction (yields and quality) and whole exome sequencing (depths of coverage and exome coverage obtained) results from this study will be presented. For RNA-sequencing, sixty-seven high-grade serous ovarian adenocarcinomas from FFPE tissues which were between 7 and 31 years old were obtained from three SEER registries. Total RNA was extracted, quantified, quality assessed, and subjected to whole transcriptome sequencing. Ultimately data derived from this analysis could serve as the basis for determining the utility of archival FFPE biospecimens for characterization and discovery projects utilizing NGS technologies instead of relying on frozen biospecimens.

  Study phs000950

• Prostate Cancer and Normal Adjacent Prostate RNA-seq samples, NGS-ProToCol

  The dataset "Prostate Cancer and Normal Adjacent Prostate RNA-seq samples, NGS-ProToCol" includes 41 Normal Adjacent Prostate and 51 ribo-depleted Prostate Cancer RNA-seq samples. ---- Detection of fusion transcripts and their genomic breakpoints from RNA sequencing data Youri Hoogstrate, Malgorzata A. Komor, René Böttcher, Job van Riet, Harmen J. G. van de Werken, Stef van Lieshout, Ralf Hoffmann, Evert van den Broek, Anne S. Bolijn, Natasja Dits, Daoud Sie, David van der Meer, Floor Pepers, Chris H. Bangma, Geert J. L. H. van Leenders, Marcel Smid, Pim French, John W.M. Martens, Wilbert van Workum, Peter J. van der Spek, Bart Janssen, Eric Caldenhoven, Christian Rausch, Mark de Jong, Andrew P. Stubbs, Gerrit A. Meijer, Remond J.A. Fijneman, Guido Jenster

  Study EGAS00001002816

• Illumina TSO500 RNA Dataset for Manuscript titled: Evaluation of Endobronchial Ultrasound-Guided Transbronchial Needle Aspiration (EBUS-TBNA) Samples from Advanced Non-Small Cell Lung Cancer for Whole Genome, Whole Exome and Comprehensive Panel Sequencing

  Illumina TSO500 RNA Dataset for Manuscript titled: Evaluation of Endobronchial Ultrasound-Guided Transbronchial Needle Aspiration (EBUS-TBNA) Samples from Advanced Non-Small Cell Lung Cancer for Whole Genome, Whole Exome and Comprehensive Panel Sequencing

  Dataset EGAD00001015397

• Bulk and single-cell RNA-sequencing data from five lines of human iPSC-derived (hiPSC-derived) astrocytes (3 in-house and 2 commercial lines), both alone and in co-culture with neurons, to define the molecular response of astrocytes to misfolded alpha-synuclein

  RNA editing is a post transcriptional mechanism that targets changes in RNA transcripts to modulate innate immune responses. We report the role of astrocyte specific, ADAR1 mediated RNA editing in neuroinflammation in Parkinson’s disease. We generated hiPSC-derived astrocytes, neurons and co-cultures and exposed them to small soluble alpha-synuclein aggregates. Oligomeric alpha-synuclein triggered an inflammatory glial state associated with TLR activation, viral responses, and cytokine secretion. This reactive state resulted in loss of neurosupportive functions, and the induction of neuronal toxicity. Notably, interferon response pathways were activated leading to upregulation, and isoform switching of the RNA deaminase enzyme, ADAR1. ADAR1 mediates A-to-I RNA editing, and increases in RNA editing were observed in inflammatory pathways in cells, as well as in post-mortem human PD brain. Aberrant, or dysregulated, ADAR1 responses and RNA editing may lead to sustained inflammatory reactive states in astrocytes triggered by alpha-synuclein aggregation, and this may drive the neuroinflammatory cascade in Parkinson’s.

  Study EGAS50000000751

• Application of targeted long-read methylation sequencing to dissected breast cancer tissues

  Four regions defined by pathological view were dissected from fresh frozen sections of breast cancer tissue using Millisect system. DNA and RNA extracted from the dissected tissues were applied to short-read WGS, short-read RNA-seq, short-read EM-seq, and targeted long-read methylation analysis t-nanoEM.

  Study JGAS000758

• Comprehensive molecular and clinicopathological profiling of desmoid tumors

  Previous studies have not clearly identified a prognostic factor for desmoid tumors (DT). Whole-exome sequencing and/or RNA sequencing were performed in 64 cases of DT to investigate the molecular profiles in combination with the clinicopathological characteristics.

  Study JGAS000270

• Genome-wide integrative analysis of pediatric pancreatoblastoma

  Pancreatoblastoma is the most common pancreatic malignancy of young children, but its molecular pathogenesis remains poorly understood. To understand the molecular pathogenesis of pancreatoblastoma, we comprehensively analysed the whole exome sequencing, RNA sequencing, SNP array, and methylation array data of pancreatoblastoma.

  Study JGAS000088

• Whole Exome Sequencing of Uveal Melanoma

  Uveal melanoma is a rare form of melanoma that occurs in the eye and has no effective treatment once metastatic. To further characterize the genomic events driving uveal melanoma, whole exome sequencing was performed on 61 primary tumors derived from enucleations, 3 liver metasases, and paired normal DNA. Recurrent somatic genetic alterations including point mutations, small insertions and deletions, as well as copy number variations were identified. In addition, RNA sequencing of uveal melanoma cell lines expressing shRNAs was performed from total RNA as well as polysome-associated mRNA in order to identify transcripts regulated by EIF1AX at the level of translation.

  Study phs001370

• SPECTA Lung cancer RNA FASTQ files

  SPECTA Lung cancer RNA FASTQ files (Illumina TST170 targeted analysis)

  Dataset EGAD00001006222

• RNA Sequencing of ECOG-E1308

  This study reports the RNA sequencing of HPV positive oropharyngeal squamous cell carcinoma samples from patients with HPV-associated stage III or stage IV cancer of the oropharynx that was surgically resectible. These patients participated in the ECOG-E1308 trial, a phase II trial that studied paclitaxel, cisplatin, and cetuximab followed by cetuximab and two different doses of intensity-modulated radiation therapy.

  Study phs003320

• HipSci RNA sequencing for embryonic stem cell control lines

  The HipSci project brings together diverse constituents in genomics, proteomics, cell biology and clinical genetics to create a UK national iPS cell resource and use it to carry out cellular genetic studies. In this sub-study we perform RNA sequencing on commercially available embryonic stem cell lines as control samples against which to compare HipSci's iPS cell lines.

  Study EGAS00001001727

• Single cell RNA sequencing of bone marrow mononuclear cells

  Bone marrow aspirates were obtained from patients with relapsed/refractory large B cell lymphoma (rrLBCL), mononuclear cells isolated by ficoll density-gradient centrifugation, and loaded onto a 10X Chromium for single cell RNA-sequencing using 5’ chemistry without prior cryopreservation. Healthy donor bone marrow mononuclear cells were obtained from healthy allogeneic stem cell transplant donors and analyzed following viable cryopreservation.

  Study EGAS00001006836

• Identification of gene mutations and fusion genes in patients with Sézary Syndrome

  Sezary syndrome (SS) is a leukemic form of cutaneous T-cell lymphoma (CTCL) with an aggressive clinical course. The goal of our study is to understand the genetic basis of the disease by looking for driver gene mutations and fusion genes in 15 erythrodermic patients with circulating Sezary cels, fourteen of them fulfilling the diagnostic criteria of SS. Peripheral blood samples were collected for each patient and CD4+ T-lymphocytes and Granulocytes were isolated. DNA and RNA was extracted for matched normal and tumor materials. Whole exome sequencing was performed on matched normal and tumor tissues of 12 patients and RNA sequencing was performed on 10 patients. For 7 of these patients, we have both exome as well as RNA sequencing data. In this study, we present a complex genomic landscape of Sezary syndrome with several point mutations, copy number variations and fusion events which could contribute to the pathogenesis of SS.

  Study EGAS00001001706

• RNA-sequence analysis in patients with inclusion body myositis

  This study aimed to elucidate the molecular features of inclusion body myositis (IBM). We performed RNA sequencing analysis of muscle biopsy samples from myositis patients with the pathological finding of CD8-positive T cells invading non-necrotic muscle fibers expressing major histocompatibility complex class I (IBM, polymyositis, and unclassifiable myositis), and controls.

  Study JGAS000068

• DIGEST: Dietary Influences on Glucuronidation, a Cross-Sectional Study of Diet and Metabolism

  Plasma samples derived from a study population of control participants (DIGEST: Dietary Influences on Glucuronidation, a Cross-Sectional Study of Diet and Metabolism) were used to profile miRNA circulating in plasma. RNA was isolated from plasma samples using the Qiagen miRNeasy kit. Libraries were prepared using Illumina TruSeq Small RNA Library Prep Kit. Libraries were sequenced on a HiSeq. Data from this sequencing project will be available through dbGaP.

  Study phs003223

• Expression profiling of Gorlin iPSCs in the osteoblast induction culture

  In this study, we utilized human induced pluripotent stem cell (iPSC)-based models of the two diseases, named Gorlin syndrome and McCune Albright synfrome, to understand the roles of Hh signaling in osteogenesis, especially in mineralization. To examine which signaling pathways and genetic networks were affected by Gorlin syndrome-associated PTCH1 mutation in human osteoblastogenesis, we performed RNA sequencing (RNA-seq) analysis in the osteoblast induction culture of WT and Gorlin iPSCs.

  Study JGAS000218

• Effect of inflammation on human hematopoietic stem cells in a xenograft model

  Transcriptional heterogeneity in cord blood HSCs was investigated by 10X single-cell Multiome (RNA+ATAC). To investigate the effect of inflammatory stress on human HSC, 10X single-cell Multiome profiling of cells from xenografted mice recovered from repeated inflammatory challenge was performed. To investigate transmission of inflammatory stress-related molecular programs from HSC to their progeny, 10X single-cell RNA sequencing was performed on committed progenitor and myeloid cells from the same mice.

  Study EGAS50000001624

• Evolution of Core Archetypal Phenotypes in High-Grade Serous Ovarian Cancer (HGSOC)

  The evolution of resistance in high-grade serous ovarian cancer (HGSOC) cells in response to chemotherapy is only partially understood. To uncover phenotypic changes associated with chemotherapy resistance, we performed single-cell RNA-sequencing (scRNA-seq) or whole-genome sequencing of 23 total patients, with longitudinal samples collected from 9, treatment-naïve samples from 8 patients, and post-treatment samples from 6 patients. Our study revealed that the HGSOC transcriptome could be described using three core archetypal phenotypes, defined as oncogenic tasks that describe majority of the transcriptional data. We implemented a multi-task learning approach to identify the biological tasks of each archetype and identified metabolism and proliferation, cellular defense response, and DNA repair signaling. The “metabolism and proliferation” archetype evolved during treatment and was enriched in cancer cells from patients that received multiple-lines of treatment and had elevated tumor burden indicated by CA-125 levels. The emergence of archetypes was not consistently linked to specific whole-genome driver mutations. However, archetypes were closely associated with sub-clonal clusters at the single-cell level, indicating that cancer cell sub-populations specialize in particular biological tasks. Our study reveals a defining principle of ovarian tumor evolution using temporal scRNA-seq profiles, identifies the key phenotypic features across patients and links metabolic shifts with a response to chemotherapy.

  Study phs002294

• BIRC5 Upregulation Enhances DNMT3A-Mutant T-ALL Cell Survival and Pathogenesis

  The goal of this study was to determine how patients with T-ALL who have DNA methyltransferase 3 alpha (DNMT3A) mutations develop resistance to therapy. Since DNMT3A is a methyltransferase, we examined the effect of those mutations on epigenetic regulation using whole genome bisulfite sequencing (WGBS). We also assessed any changes in gene expression using RNA-sequencing. We found that T-ALL patients with DNMT3A mutations are resistant to apoptosis and some chemotherapies. WGBS showed that DNMT3A mutated patients clustered together by their epigenetic profile, which was associated with hypomethylation at TERT and HOX genes. RNA sequencing identified differences in JAK/STAT signaling.

  Study phs003623

• Identification of RNA biomarkers in Parkinson's disease patients

  Parkinson?s disease (PD) is an age-related, chronic and progressive neurodegenerative disorder characterized by a loss of dopaminergic neurons and subsequent motor symptoms. These overt motor symptoms are often preceded by prodromal non-motor symptoms. Though a number of genetic and environmental factors have been identified to play a role in PD, more exact methods for both diagnosing and assessing prognosis are yet to be discovered. By analyzing the transcriptome of early-stage PD patients, this study aims to identify genes (including important non-coding RNAs) and pathways altered at disease onset that may be used as novel biomarkers for PD diagnosis as well as potential new drug targets. The study consists of three main sources of data: first year blood transcriptomes, second year blood transcriptome and matched neural stem cell (NSC)/neuron transcriptomes. All transcriptome libraries were synthesized and sequenced using no-amplification non-tagging cap analysis of gene expression (nAnT-iCAGE) on the Illumina HiSeq 2500 platform. Resulting data was mapped to the human genome annotation (hg38), processed CAGE tags were clustered ready for differential expression analyses. First year blood sequencing consisted of 22 PD patients and 10 healthy controls across four lanes. In the second year, a further four lanes were sequenced containing 17 PD patients (12 patients from the first year and 5 new patients) along with 10 healthy controls and 5 first year blood samples matching the new second year patients.

  Study JGAS000119

• Genome analysis of common diseases among older Japanese adults and development of clinical genome information storage

  A comprehensive gene expression analysis of the process leading up to the onset of Alzheimer???s disease (AD) would be helpful for understanding the mechanism. We performed an RNA sequencing analysis on a cohort of 1227 Japanese blood samples, representing 424 AD patients, 543 individuals with mild cognitive impairment (MCI), and 260 cognitively normal (CN) individuals. A total of 883 and 1169 statistically significant differentially expressed genes (DEGs) were identified between CN and MCI (CN-MCI) and between MCI and AD (MCI-AD), respectively. Pathway analyses using these DEGs, followed by protein???protein interaction network analysis, revealed key roles of ribosomal genes (RPL7, RPL11, and RPL14) and phagosomes (CDC42, PTPRC, PLCG1, and ACTR2) in MCI progression, whereas immune-related genes were involved in AD progression. Given the known effectiveness of delaying MCI progression in preventing AD, the genes related to ribosomal function and phagocytosis might emerge as biomarkers for early diagnosis.

  Study JGAS000755

• Human CD4+ T cells regulate peripheral immune responses in rheumatoid arthritis via IGFL2

  To elucidate the role of the immunoregulatory mechanisms of human CD4+ T cells, we analyzed CD4+ T cells in PBMC, synovium and synovial fluid using single-cell RNA sequencing (scRNA-seq). We identified insulin-like growth factor (IGF) like family member 2 (IGFL2), an evolutionary novel paralogous inflammatory factor found exclusively in primates. ScRNA-seq of RA synovium showed that IGFL2 is specifically expressed by CD4+ T cells, predominantly within peripheral helper T (Tph) cells, with upregulation correlating to disease severity. IGFL2 promotes TGF-��-induced CXCL13 production in CD4+ T cells. In addition, IGFL2 activates NF-��B signaling and induces monocyte gene signatures associated with pathogenic macrophages from RA synovial tissue, including CXCL10 and CXCL9. Notably, blood IGFL2 protein levels significantly correlate with RA disease severity and effectively discriminate RA patients. These findings highlight the substantial involvement of IGFL2 in RA pathogenesis, emphasizing how human CD4+ T cells exert pleiotropic regulation of local immune responses via this novel primate-specific soluble factor.

  Study JGAS000727

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

  To elucidate the regulation of gene expression in immune cell subsets and its contribution to autoimmune diseases, Whole blood and various immune cell subsets from 119 Systemic Lupus Erythematosus (SLE), 65 Dermatomyositis & Polymyositis, 67 Systemic Sclerosis, 19 Mixed Connective Tissue Disease, 18 Sjogren's syndrome, 24 Rheumatoid Arthritis, 23 Behcet's disease, 18 Adult Onset Still���s Disease, 25 ANCA-associated Vasculitis, 16 Takayasu���s Arteritis and 141 healthy controls (C) were collected (Naive_CD4, Mem_CD4, Fr._I_nTreg, Fr._II_eTreg, Fr._III_T, Th1, Th2, Th17, Tfh, NK, Naive_CD8, Mem_CD8, EM_CD8, CM_CD8, TEMRA_CD8, Naive_B, USM_B, SM_B, DN_B, Plasmablast, CL_Mono (or CD16n_Mono), CD16p_Mono, Int_Mono, NC_Mono, mDC, pDC, LDG, Neu). Whole genome sequencing was performed with whole blood samples. RNA-seq was performed with each immune cell subset samples. After filtering and normalization of the gene expression data, eQTL analysis was performed in each immune cell type. 15 immune cell subsets ATAC-seq was also performed in 8 SLE and HCs, each.

  Study JGAS000220

• Single cell sequencing data of PBMC and CSF from a cohort of Multiple Sclerosis patients and other neurological disease controls

  Neuroinflammation is often characterised by immune cell infiltrates in the cerebrospinal fluid (CSF). Here we apply single-cell RNA sequencing to explore the functional characteristics of these cells in patients with various inflammatory, infectious and non-inflammatory neurological disorders. We show that CSF is distinct from the peripheral blood in terms of both cellular composition and gene expression. We report that the cellular and transcriptional landscape of CSF is altered in neuroinflammation, but is strikingly similar across different neuroinflammatory disorders. We find clonal expansion of CSF B and T cells in all disorders but most pronounced in inflammatory diseases, and we functionally characterise the transcriptional features of these cells. Finally, we explore the genetic control of gene expression in CSF lymphocytes. Our results highlight the common features of immune cells in the CSF compartment across diverse neurological diseases and may help to identify new targets for drug development or repurposing in Multiple Sclerosis.

  Study EGAS50000000739

• GATA6 expression distinguishes classical and basal-like subtypes in advanced pancreatic cancer.

  PURPOSE: To determine the impact of basal-like and classical subtypes in advanced PDAC and to explore GATA6 expression as a surrogate biomarker. EXPERIMENTAL DESIGN: Within the COMPASS trial patients proceeding to chemotherapy for advanced PDAC undergo tumour biopsy for RNA sequencing. Overall response rate (ORR) and overall survival (OS) were stratified by subtypes and according to chemotherapy received. Correlation of GATA6 with the subtypes using gene expression profiling, in situ hybridization (ISH) were explored. RESULTS: Between December 2015-May 2019, 195 patients (95%) had enough tissue for RNA sequencing; 39 (20%) were classified as basal-like and 156 (80%) as classical. RECIST response data were available for 157 patients; 29 basal-like and 128 classical where the ORR was 10% vs. 33% respectively (p=0.02). In patients with basal-like tumours treated with modified FOLFIRINOX (mFFX) (n=22) the progression rate was 60% compared to 15% in classical PDAC (p= 0.0002). Median OS in the intention to treat population (n=195) was 9.3 months for classical vs. 5.9 months for basal-like PDAC (HR 0.47 95% CI 0.32-0.69, p=0.0001). GATA6 expression by RNAseq highly correlated with the classifier (p<0.001) and ISH predicted the subtypes with sensitivity of 89% and specificity of 83%. In a multivariable analysis, GATA6 expression was prognostic (p=0.02). In exploratory analyses, basal-like tumours, could be identified by keratin 5, were more hypoxic and enriched for a T cell inflamed gene expression signature. CONCLUSIONS: The basal-like subtype is chemoresistant and can be distinguished from classical PDAC by GATA6 expression.

  Dataset EGAD00001006081

• Understanding the Progression of Metastatic Colorectal Cancer

  This study is to understand (1) the clonal evolution of metastatic colorectal cancer using DNA sequencing and (2) long non-coding RNAs associated with metastatic colon cancer using RNA sequencing. Our goal is to better understand the progression of aggressive colorectal cancer.

  Study phs001722

• Integrated genetic and epigenetic analysis of myxofibrosarcoma

  Myxofibrosarcoma (MFS) is a common histological subtype of adult soft tissue sarcoma characterized by an infiltrative growth pattern and a high propensity for local recurrence. We underwent whole exome sequencing, RNA sequencing, and methylation analysis of MFS.

  Study EGAS00001002889

• Genomics of Acute Myeloid Leukemia

  Sequence data from the Genomics of AML PPG program at Washington University since 2009 is made available. This repository contains data from tumors (bone marrow or peripheral blood) from Acute Myeloid Leukemia (AML) and several other related disorders - myelodysplastic syndromes (MDS), secondary AML (sAML) and therapy-related AML (tAML). It also contains matched normal data (skin or buccal swab) and healthy donors for comparison. A variety of DNA sequencing assays were used, including whole genome sequencing (WGS), exome sequencing, targeted panels of AML genes, or targeted panels for validation. Other modalities, including RNA-seq, small RNA-seq, whole genome bisulfite sequencing, CHIP-seq, ATAC-seq, and single-cell RNAseq are also represented.

  Study phs000159

• Characterization of Structural Variants in Acute Myeloid Leukemia Patients

  Acute myeloid leukemia (AML) is the most common form of acute leukemia in adults and is expected to increase in frequency as the population ages. Most subtypes of AML are difficult to treat, in part due to a lack of understanding of possible molecular targets. Furthermore, the peak incidence of AML is in the sixth decade, and patients over the age of 65 do not tolerate chemotherapeutic regimens well. Moreover, AML has been highly studied as a model for other cancers. An RNA Biology Program is established aiming to develop comprehensive datasets through the profiling of all different classes of RNA expression, RNA editing, alternative splicing, and non-coding RNAs in CD34+ normal hematopoietic stem cells (HSC), their differentiated progeny, and AML clinical samples that could be utilized to understand leukemia. These datasets will allow us to computationally identify and characterize various RNA species and processes to enable the development of effective therapeutics to AML, leukemia and other types of cancers. Epigenetic factors such as methylation and histone modifications will also be characterized from these clinical samples allowing for integrated dataset analysis to look at the cross-talk between RNA and DNA/epigenomics in leukemia. The following is a subsidiary study of the above study description where whole genome sequencing was performed on two collected AML patients' samples using Illumina and Oxford Nanopore sequencing technologies. The aim is to characterize the roles of structural variants (SV) in RNA biology which are potentially important for AML development using our own established long-read SV characterization tool, NanoVar. The advent of Oxford Nanopore sequencing technologies has opened a new avenue for better SV characterization by having longer sequencing reads. NanoVar is an accurate and rapid SV characterization tool that utilizes low-depth Nanopore sequencing data. NanoVar makes use of split-reads and hard-clipped reads for SV discovery and employs a simulation-trained neural network classifier for true positive enrichment. NanoVar exhibited higher accuracy and faster computational speed amongst other long-read SV detection tools in simulated data. In AML patient data, NanoVar displayed excellent accuracy in SV characterization (16/16 SVs validated in two patients) by using only 4x depth sequencing data. In summary, NanoVar improves the accuracy and speed of SV characterization at a lower sequencing cost, an approach compatible with clinical studies.

  Study phs001847

• RNA-seq of multiple myeloma patient samples

  RNA from CD138+ plasma cells from patients with a plasma cell dyscrasia were sequenced using the TruSeq Stranded Total RNA Ribo-zero Gold kit (Illumina). Paired-end 75bp reads were generated on a NextSeq500 or HiSeq4000 (Illumina). The dataset consists of 1 MGUS sample, 5 SMM samples, 69 newly diagnosed myeloma samples, 1 relapsed myeloma sample, 1 previously treated myeloma samples, and 4 PCL samples. Matching whole genome sequencing data are available for these samples under study EGAS00001003164.

  Dataset EGAD00001004543

• To profile the landscape of sebaceous tumours_RNAseq

  Sebaceous tumours are a rare cutaneous cancer with potential for aggressive behaviour. However, limited information is available on these cancers with few published cases. Here we wish to exome sequence these cancers to define the first genomic landscape for this malignancy. We will extract RNA from formalin-fixed, paraffin-embedded (FFPE) cores. Cores may be obtained from lesional and non-lesional tissues of primaries as well as matching metastases. The extracted RNA will be used for RNA sequencing.

  Dataset EGAD00001015368

• WGS, RNA-seq and methyl-seq data for multiple tumour clones from a single glioblastoma case.

  10 bams of WGS data from HiSeqXTen platform; 10 bams of RNA-seq data from HiSeq2500 platform; 7 bams of TruSeq Methyl Capture EPIC sequencing data from HiSeq4000 platform

  Dataset EGAD00001004773

• Presence of bacterial infection in brains of patients with Huntington's disease (HD)

  Bacterial isolation in infected brains in patients with Huntington's disease. Here we used next generation sequencing of 16S ribosomal RNA gene PCR amplicons (NGS 16S amplicon analysis)

  Study EGAS00001003678

• Presence of bacterial infection in brains of patients with Parkinson's disease (PD)

  Isolation of bacteria in infected brains in patients with Parkinson's disease. Here we used next generation sequencing of 16S ribosomal RNA gene PCR amplicons (NGS 16S amplicon analysis).

  Study EGAS00001003643

• Chronic lymphocytic leukemia patient-derived xenografts recapitulate clonal evolution to Richter transformation

  Whole-genome sequencing (WGS) and RNA-seq data from patient-derived xenografts (PDXs) obtained from CLL and RT primary samples as described in Playa-Albinyana et al.

  Study EGAS00001006965

• ICGC PedBrain: RNA sequencing

  ICGC PedBrain: RNA sequencing

  Dataset EGAD00001000328

• Gene Expression Signatures Characterized by Longitudinal Stability and Inter-Individual Variability Delineate Baseline Phenotypic Groups with Distinct Responses to Immune Stimulation

  RNA sequencing (RNAseq) of peripheral blood lymphocytes was used to develop a means to assess immune function in a way that can be used in discovery science and applied to patients individually in clinical settings. The premise is that profiles of RNA present in immune cells is reflective of the combined influence of genetic and environmental variation on immune potential of individuals and that this potential can be tapped to understand human immunity in a variety of biological contexts. CD4+ cells were isolated from fresh whole blood via positive magnetic bead selection and cell lysates were prepared using Qiazol (QIAGEN) and stored at -80ºC for 3 to 8 months. RNA was extracted in batches for cDNA library preparation and RNA-Seq. For this study, we developed standard operating procedures for handling human blood samples and determined: a) the best way to enrich for CD4+ T cells from whole blood and yield high quality RNA, b) the sensitivity of this RNA profiling strategy, and c) the reproducibility of generated immune profiles from healthy subjects. We then developed bioinformatics processes to establish immune response signatures and immune response phenotypes within cohorts of individuals.

  Study phs001512

• Development and Validation of Patient-Derived Xenografts from Fibrolamellar Carcinoma Human Tissue

  We developed and validated Patient-Derived Xenografts (PDX) of Fibrolamellar Carcinoma human tissue from surgical resections. Human tissues from primary liver tumor, recurrent liver, and liver metastases were implanted into NOD-SCID-Gamma (NSG) mice (Jackson laboratories) and monitored for tumor growth. Some of the original tissues were frozen for further analysis including RNA sequencing. Tumors that grew were then harvested and passaged into additional mice. Some tumor tissues from the PDX samples were frozen for RNA-Seq analysis. The PDX was validated by histologic, transcriptomic and proteomic analysis. The RNA-Seq analysis was performed on original tissue samples including primary liver tumor, recurrent liver, liver metastases, normal liver, and the derived PDX.

  Study phs002435

• Transcriptomics of PPD and Control LCLs Exposed to Steroid Hormones

  Lymphoblastoid cell lines (LCLs) were derived from women with (n=11) and without (n=9) past postpartum depression (PPD) and compared transcriptomically in two studies. Data provided represents: 1) normalized RNA-seq expression (CPM) or 2) Ampliseq-RNA Expression (CPM).The two studies are described below.1) The first examined estradiol (E2) and progesterone (P) hormone conditions mimicking pregnancy and parturition: supraphysiologic E2+P-addback; supraphysiologic E2+P-withdrawal; and no added E2+P (Baseline). RNA-sequencing identified unique differentially expressed genes (DEGs, p2) The second exposed control and PPD LCLs to ALLO or DMSO vehicle for 60 hours and used Ampliseq to detect differentially expressed genes (DEGs, pnominal

  Study phs003820

• Single-cell RNA sequencing on single CD45+ immune cells isolated from peripheral blood, lymphnode, ascites, tumour and adjacent normal tissues from six hepatocellular carcinoma patients.

  Single-cell RNA sequencing on single CD45+ immune cells isolated from peripheral blood, lymphnode, ascites, tumour and adjacent normal tissues from six hepatocellular carcinoma patients. The transcriptional properties of these individual cells, were used to delineate the molecular subtypes, lineage, and functional properties of each cell group

  Study EGAS00001003449

• The Genetic and Transcriptomic Evolution of Melanoma

  The overarching goal of the study was to better understand the evolution of melanoma. To do this, we collected archival tissue of melanomas adjacent to their intact, remnant precursor lesions. We also collected archival tissue of primary melanomas and their matching metastases. From the formalin-fixed paraffin-embedded (FFPE) blocks, we microdissected non-neoplastic (normal), precursor, and descendent portions of tissue. Both RNA and DNA were extracted from the microdissected tissues and subjected to next generation sequencing. In summary, we performed matched DNA/RNA sequencing of melanoma/precursor/normal trios, allowing us to trace the genetic and transcriptomic evolution of melanoma.

  Study phs001550

• scRNA-seq of patient-derived PDAC organoids and matched CAFs

  We established direct three-dimensional (3D) co-cultures of primary PDAC organoids and patient-matched CAFs. Single-cell RNA sequencing was performed for three organoid/CAF pairs in mono- and co-culture to uncover transcriptional changes induced by tumor-stroma interaction. Single-cell RNA sequencing data evidenced induction of a pro-inflammatory phenotype in CAFs in co-cultures. Organoids showed increased expression of genes associated with epithelial-to-mesenchymal transition (EMT) in co-cultures and several potential receptor-ligand interactions related to EMT were identified, supporting a key role of CAF-driven induction of EMT in PDAC chemoresistance.

  Study EGAS00001006661

• Application of organoid culture system of human gastrointestinal and thoracic cancer in genome medicine

  In order to establish preclinical models, we have established a kind of lung cancer tumoroids derived from a mucus-producing solid pulmonary adenocarcinoma patient. We performed whole exome sequencing and RNA sequencing to analyze genetic background of the tumoroids.

  Study JGAS000664

• Application of organoid culture system of human gastrointestinal and thoracic cancer in genome medicine

  In order to establish preclinical models, we have established a kind of lung cancer tumoroids derived from a mucus-producing solid pulmonary adenocarcinoma patient. We performed whole exome sequencing and RNA sequencing to analyze genetic background of the tumoroids.

  Study JGAS000653

• Indonesian RNA-seq data

  Transcription data were collected to study patterns of functional variation across the broad geography of Indonesia. The region has extremely diverse populations, with very different demographic histories and multiple genetic ancestries. This dataset reports high-throughput RNA-sequencing data for individuals from three islands spanning this geographical region: Mentawai, Sumba and West Papua.

  Study EGAS00001003671

• RNA-Seq

  RNA Sequencing

  Dataset EGAD00001001121

• Regulatory Changes in Glioblastoma Brain Tumors and Xenografts Wave 1

  Non-coding elements in our genomes that play critical roles in complex disease are frequently marked by highly unstable RNA species. Sequencing nascent RNAs attached to an actively transcribing RNA polymerase complex can identify unstable RNAs, including those templated from gene-distal enhancers (eRNAs). However, nascent RNA sequencing techniques remain challenging to apply in some cell lines and especially to intact tissues, limiting broad applications in fields such as cancer genomics and personalized medicine. Here we report the development of chromatin run-on and sequencing (ChRO-seq), a novel run-on technology that maps the location of RNA polymerase using virtually any frozen tissue sample, including samples with degraded RNA that are intractable to conventional RNA-seq. We used ChRO-seq to develop the first maps of nascent transcription in 23 human glioblastoma (GBM) brain tumors and patient derived xenografts. Remarkably, >90,000 distal enhancers discovered using the signature of eRNA biogenesis within primary GBMs closely resemble those found in the normal human brain, and diverge substantially from GBM cell models. Despite extensive overall similarity, 12% of enhancers in each GBM distinguish normal and malignant brain tissue. These enhancers drive regulatory programs similar to the developing nervous system and are enriched for transcription factor binding sites that specify a stem-like cell fate. These results demonstrate that GBMs largely retain the enhancer landscape associated with their tissue of origin, but selectively adopt regulatory programs that are responsible for driving stem-like cell properties. We also identified enhancers and their associated transcription factors that regulate genes characteristic of each known GBM subtype, and discovered a core group of transcription factors that control the expression of genes associated with clinical outcomes. This study uncovers new insights into the molecular etiology of GBM and introduces ChRO-seq which can now be used to map regulatory programs contributing to a variety of complex diseases.

  Study phs001646