3786 results for "RNA AND sequencing OR transcriptome"

in 21.27 milliseconds.

• 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, 24 peripheral blood immune cell subsets from 50 Systemic Sclerosis and 48 Healthy Controls were collected (Naive_CD4, Mem_CD4, Fr._I_nTreg, Fr._II_eTreg, Fr._III_T, Th1, Th2, Th17, Tfh, NK, Naive_CD8, EM_CD8, CM_CD8, TEMRA_CD8, Naive_B, USM_B, SM_B, DN_B, Plasmablast, CL_Mono, Int_Mono, NC_Mono, mDC, pDC). RNA-seq was performed with each immune cell subset samples. After gene expression quantification samples were filtered.

  Study JGAS000296

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

  Various peripheral blood immune cell subsets from 89 healthy volunteers and 136 systemic lupus erhythematosus (SLE) donors were collected (Naive_CD4, Mem_CD4, Th1, Th2, Th17, Tfh, Fr._I_nTreg, Fr._II_eTreg, Fr._III_T, Naive_CD8, EM_CD8, CM_CD8, TEMRA_CD8, NK, Naive_B, USM_B, SM_B, DN_B, Plasmablast, CL_Mono (or CD16n_Mono), CD16p_Mono, Int_Mono, NC_Mono, mDC, pDC, Neu, LDG). 22 SLE donors were analyzed longitudinally. RNA-seq was performed with each immune cell subset samples. After gene expression quantification samples were filtered.

  Study JGAS000486

• RNA-Seq dataset for Genomic rearrangements in Pediatric Cancer

  RNA-Seq data for systematic gene fusion detection in Pediatric Cancer

  Dataset EGAD00001008152

• BAM files of total RNA-Seq data of POPS control samples (GRCh37)

  Placental biopsies (n = 64 female placentas, n = 67 male placentas) were selected from healthy pregnancies from the POPs cohort. A quality control process was also applied for the RNA-Seq datasets: reads were trimmed with Trim Galore!, which uses cutadapt internally and were mapped to the same version of human genome reference (hg19). TopHat2, a splice-aware mapper built on top of Bowtie2 short-read aligner, was used in the mapping process in which so-called two-pass (or two-scan) alignment protocol was applied to rescue unmapped reads from the initial mapping step. In the second mapping, previously unmapped reads were re-aligned to the exon-intron junctions detected in the first-mapping by TopHat2 and were combined across all 131 placenta samples. The initial and second mapped reads were merged by samtools

  Dataset EGAD00001003462

• Risk Factors for Asymptomatic Diverticulosis

  Data for this analysis came from a prospective study of colonic diverticulosis at the University of North Carolina Hospital in Chapel Hill, North Carolina (NIH R01DK094738). This is a case-control genetic and transcriptomic study to identify the genetic and cellular determinants underlying colonic diverticulosis and the relationship with other gastrointestinal disorders. The study inclusion and exclusion are described below. DNA and RNA sequencing were performed on colonic tissue from 404 patients with (N=172) and without (N=232) diverticulosis. We assessed variation in the transcriptome associated with diverticulosis and integrated this variation with human intestine single-cell RNA-seq data. We integrated our expression quantitative trait loci with GWAS using Mendelian Randomization. A polygenic risk score analysis examined associations between severity of diverticulosis and other gastrointestinal disorders. We identified 38 genes with differential expression and 17 genes with varied transcript usage linked to diverticulosis. Our results suggest tissue remodeling as a primary mechanism for diverticula formation. The presence of diverticulosis was linked to stromal and epithelial cells in the colon including endothelial cells, myofibroblasts, fibroblasts, goblet, tuft, enterocytes, neurons, and glia. MR highlighted five genes including CCN3, CRISPLD2, ENTPD7, PHGR1, and TNFSF13. In diverticulosis cases, ENTPD7 upregulation was confirmed. A greater burden of diverticula was positively correlated with genetic predisposition to diverticulitis. The data related to the study including total RNA-Seq, SNP array and imputed genotypes will be available through dbGaP.

  Study phs003556

• Whole exome and transcriptome analysis of UV-exposed epidermis and carcinoma in situ reveals early drivers of carcinogenesis

  Squamous cell carcinoma in situ (SCCIS) is a prevalent precancerous lesion that can progress to cutaneous squamous cell carcinoma (cSCC). Although SCCIS is common, its pathogenesis remains poorly understood. To better understand SCCIS development, we performed laser-captured microdissection of human SCCIS and adjacent epidermis to isolate genomic DNA and RNA for next generation sequencing. Whole exome sequencing (WES) identified UV-signature mutations in multiple genes including Notch 1-3 (GeneID:4851, GeneID:4853, GeneID:4854) in the epidermis and SCCIS and oncogenic TP53 (GeneID:7157) mutations in SCCIS. Novel gene families, including SCHLAFEN genes, contained UV/oxidative-signature disruptive (UVD) epidermal mutations that manifested positive selection in SCCIS. The frequency and distribution of NOTCH and TP53 mutations indicate that NOTCH mutations may precede TP53 mutations. RNA sequencing identified 1166 differentially expressed genes; the top 5 enriched GO biological processes included: 1) immune response, 2) epidermal development, 3) protein phosphorylation, 4) regulation of catalytic activity, and 5) cytoskeletal regulation. The NEURL1 ubiquitin ligase, which targets Notch ligands for degradation, was upregulated in SCCIS. Neuralized 1 protein was found to be elevated in SCCIS suggesting that increased levels could represent a novel mechanism for downregulating Notch during UV-induced carcinogenesis. The data from DNA and RNA sequencing of epidermis and SCCIS provide insights regarding SCCIS formation.

  Study phs002019

• Single-cell characterization of human GBM reveals regional differences in tumor-infiltrating leukocyte activation

  Background: Glioblastoma (GBM) harbors a highly immunosuppressive tumor microenvironment (TME) which influences glioma growth. Major efforts have been undertaken to describe the TME on a single-cell level. However, human data on regional differences within the TME remain scarce. Goals: we performed single-cell RNA sequencing (scRNAseq) on paired biopsies from the tumor center, peripheral infiltration zone and blood of five patients with primary GBM Details: This EGA study includes raw data sequencing files for the scRNA-seq samples. The processed data (output from Alevin, UMI count matrix and cell metadata) are available from GEO https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE197543

  Study EGAS50000000302

• Determining off-target effects of splice-switching antisense oligonucleotides using short read RNAseq in neuronally differentiated human induced pluripotent stem cells

  Neuronal cells derived from female healthy control hiPSC lines LUMCi003-A, LUMCi003-B and LUMCi023-A were transfected with in total four different splice-switching AONs targeting three different human transcripts. Untransfected samples as well as samples transfected with a scrambled AON were included as controls. Three days after transfection, RNA was isolated for sequencing using Illumina Novaseq6000 in order to perform differential gene expression analysis and differential splicing analysis to determine off-target effects. Sequencing was performed in two batches: one containing the samples from cell line LUMCi003-A and the other containing cell lines LUMCi003-B and LUMCi023-A.

  Dataset EGAD50000001742

• ICARUS-LUNG01 dataset

  A total of 46 frozen tumor biopsies underwent WES analysis, while 41 blood samples were used as germline controls.Tumor samples qualified for whole exome sequencing (WES) if they contained ≥10% tumor cells. For bulk RNA-seq, 20 paired baseline and on-treatment frozen tumor biopsies were analyzed. Tumor samples qualified if they contained ≥30% tumor cells. For GeoMx spatial transcriptomic study we used 7 patients from the ICARUS LUNG01 trial focusing on tumour and immune cell compartments. We selected 7 paired baseline and on-treatment patient samples for analysis. We selected up to 4 regions of interest (ROI) per sample tissue. We identified tumour and immune cell areas of illumination (AOI) using CK and CD45 antibodies respectively

  Dataset EGAD50000001014

• Dataset for upper_gastrointestinal_tumor-RNA

  Rare cancer sequencing data of 44 runs in tumor/control pairs, which were uploaded to umbrella studies. The sequencing was always paired

  Dataset EGAD00001008853

• Tumor-derived cell lines as pharmacogenomic models to predict therapeutic vulnerabilities in hepatocellular carcinoma

  Hepatocellular carcinoma (HCC) is a heterogeneous aggressive malignancy with low efficacy of current therapies at advanced stages. We integrated molecular and pharmacological profiling of a large panel of liver cancer cell lines (LCCL) to assess their clinical relevance as HCC preclinical models and identify new effective therapies and biomarkers of response. Here, we performed multi-omic analysis including whole-exome, RNA and microRNA sequencing in a series 34 LCCL. Molecular profiles of LCCL and primary HCC were compared and we searched for molecular features associated with drug response. Our panel of LCCL faithfully recapitulated the most aggressive molecular “proliferation class” of HCC.

  Dataset EGAD00001004938

• Bulk RNAseq from in vitro generated macrophages and T cells

  Monocyte derived macrophages were polarised into M1 or M2 using IFNg+ ILP or IL-4 respectively (n =4) . Pan T cells were cultured with or without IL-2 for 4 days (n=4 - 6). Pan T cells were co-cultured with THP1 tumour cells for 20 hours in the presence or absence of ImmTAC molecules and in the presence or absence of M2 macrophages. Sorted T cells and macrophage populations prior and post co-culture were analysed by bulk RNA sequencing (60 million reads per sample) using the Illumina NovaSeq system

  Dataset EGAD50000001226

• Tumor Thrombus Dataset

  the dataset contains Exome and RNA fastq files of Renal Cell Carcinoma patients, which belongs to "Integrated genomic analysis of tumor thrombus"/

  Dataset EGAD00001008010

• Orthotopic murine Group 3 medulloblastoma in C57Bl/6 mice treated with sham or craniospinal irradiation

  Mice with medulloblastoma (Group 3) were treated with sham (isofluorane and imaging xray) or CSI as described by Abbas et al (2022). Total RNA was isolated with RNeasy Plus Mini Kit (Qiagen), library preparation (SureSelect, Agilent), rRNA depletion (Ribo-Zero Plus, Illumina) and sequencing were carried out by GenomicsWA or Australian Genome Research Facility. Libraries were sequenced on NovaSeq 6000 S1 flow cells as paired-end 150bp reads (Illumina).

  Dataset EGAD00001008510

• ProstOmics - Bulk Transcriptomics

  Bulk transcriptomics data from 176 prostate tissue samples (37 patients, 27 with post-surgery relapse) that were acquired using the SENSE mRNA-Seq Library Prep Kit V2 and Illumina NextSeq 500 instrument. The raw transcriptomics data is single-read RNA-seq. The individual samples have information on patient origin and sample type (cancer, cancer-adjacent field-effect normal or normal sample far from cancer). Patient metadata include information of age at surgery, time (months) until reported relapse, pre-surgery PSA and post-surgery T-stage.

  Dataset EGAD50000000604

• Cambridge COVID-19 Single-cell PBMC

  Single-cell multi-omic profiling of healthy controls, asymptomatic and hosptial-admitted COVID19 patients recruited from Addenbrookes and Royal Papworth hospitals, in collaboration with the NIHR Cambridge Bioresource. Data represent RNA-seq, surface protein measurements (CITE-seq) of 192 antibody targets, along with VDJ-seq profiling of single T cell and B cell receptors. Samples are pooled, with 4 donors per pool. Germ-line genotypes are provided (VCF) to aid demultiplexing of single-cell and assignment to specific patient donor samples.

  Dataset EGAD00001007867

• RNA-seq analysis of CCO+/CCO- hepatocytes in normal human liver

  RNAseq data from Passman et al 2023. Clonal CCO-deficient hepatocyte patches and nearby CCO-proficient hepatocytes were identified in morphologically normal human livers and sampled at varying distances along the PT-CV axis. Samples are characterised according to their location within the liver lobule, with "PT" denoting samples abutting the portal triad, "CV" denoting samples abutting the central hepatic vein, and "Mid" sampled acquired midway between these structures. Analysis was performed on an Illumina Nextseq using a high output kit and 100 single-end cycles.

  Dataset EGAD00001010033

• Oncogenic cooperation between the TCF7-SPI1 fusion and NRAS(G12D) requires β-catenin activity to drive T-cell acute lymphoblastic leukemia.

  In this study we investigate the role of TCF7-SPI1 fusions, more specifically in cooperation with RAS mutations. We make use of patients samples. This study contains paired-end RNA sequencing of the patients, Oxford Nanopore Technologies (ONT) sequencing, single cell RNA sequencing and RNA sequencing of treatment with inhibitors of these samples.

  Study EGAS00001005097

• Five Mantle Cell Lymphoma Patients Before and After Failure of Standard Chemotherapy

  MCL cells were isolated from different tissues of five patients with MCL at diagnosis, and at the time of the first clinical relapse after failure of standard immunochemotherapy based on alternation of R(ituximab)-CHOP and R-high-dose-araC. All patients signed informed consent according to the Declaration of Helsinki. Four patients were diagnosed with classical nodal aggressive MCL, and all these patients experienced early relapse (i.e., progression of disease POD < 12 months). One patient was diagnosed with indolent non-nodal MCL and relapsed 9 years after initial MCL diagnosis. The dataset presents single cell RNA sequencing data as well as whole exome sequencing data for these five patients.

  Dataset EGAD50000001213

• Cell line data (RNAseq, ATACseq, ChIPseq)

  Content: 2 GB RTK I cell lines (LN229, ZH487) in two conditions (NT control and shSOX10). RNAseq: single replicates per condition, polyA+ RNA sequencing, SE. ATACseq: biological replicates per condition, SE. ChIPseq (histone H3 modifications, LN229 only): all marks for each condition were pooled and sequenced on two lanes for each pool. ChIPseq (BRD4 and SOX10): SOX10 libraries were sequenced on single lanes. BRD4 samples were multiplexed and sequenced in two lanes. ChIPseq input samples are also included. Data type and technology: RNAseq: SE 50bp sequenced on HiSeq2000/4000. ATACseq: SE 50bp sequenced on HiSeq2000/4000. ChIPseq: SE 50bp sequenced on HiSeq2000/4000.

  Dataset EGAD00001005493

• UCSF-CASCADE analysis of metastatic prostate cancer

  Targeted cancer therapy inevitably selects for tumor cells that harbor some form of therapy resistance. This phenomenon is a principle reason why advanced prostate cancer, which can be treated with agents targeting androgen signaling dependency and DNA repair failure, is a lethal condition. The influence of a patient's clinical history and disease evolution on how their disseminated tumors develop resistance has been difficulty to study, because few autopsy studies have been performed in heavily treated patients with DNA-repair deficient metastatic castration-resistant prostate cancer (mCRPC). Here, we assessed how resistance to targeted cancer therapies evolved in an autopsy cohort of 54 mCRPC tumors from six men. This dataset includes targeted sequencing, exome sequencing, and RNA-seq conducted on these biopsies.

  Dataset EGAD00001010275

• UMCU_Molpheno_Restricted

  This dataset contains Whole Genome Sequencing and, if available, RNA-sequencing and/or ATAC-sequencing data obtained from PBMCs derived from blood samples of 34 patients with intellectual disability and/or multiple congenital anomalies and their biological parents (58) included in the University Medical Center Utrecht (The Netherlands).

  Dataset EGAD00001004865

• Personalized RNA mutanome vaccines mobilize poly-specific therapeutic immunity against cancer RNA-Seq

  The goal of the sequencing study was to determine the neoantigen profile of melanoma patients. We performed whole exome sequening of the tumor and respective patien matched PBMC samples (2x50nt) and RNA-sqeuencing of the tumor samples. The was analyzed for somatic point mutaions, using the RNA-Seq data to determine mutation expression. This study contains the patient matched RNA-Sequencing data.

  Study EGAS00001003307

• RNA-sequencing of HCC patients undergoing sorafenib treatment

  RNA-sequencing of hepatocellular carcinomas at various stages of sorafenib treatment

  Study EGAS00001005662

• Whole-genome landscape of adult T-cell leukemia/lymphoma

  Whole-genome sequencing (WGS) data of tumor-normal pairs from 139 ATL patients and RNA sequencing (RNA-seq) data of tumors from 28 ATL patients.

  Study EGAS00001005237

• Non-invasive human skin transcriptome analysis using mRNA in skin surface lipids

  Non-invasive acquisition of mRNA data from the skin can be extremely useful for understanding skin physiology and diseases. Inspired by the holocrine process, in which the sebaceous glands secrete cell contents into the sebum, we focused on the possible presence of mRNAs in skin surface lipids (SSLs). We found that measurable levels of human mRNAs exist in SSLs, where the sebum protects them from degradation by RNases. The AmpliSeq transcriptome analysis was modified to measure SSL-RNA levels, and our results revealed that the SSL-RNAs predominantly comprised mRNAs derived from sebaceous glands, the epidermis, and hair follicles. Analysis of SSL-RNAs non-invasively collected from patients with atopic dermatitis revealed significantly increased expression of inflammation-related genes and decreased expression of terminal-differentiation���related genes, consistent with the results of previous reports. Further, we found that lipid-synthesis���related genes were downregulated in the sebaceous glands of patients with atopic dermatitis. These results indicate that the analysis of SSL-RNAs is a promising strategy to understand the pathophysiology of skin diseases.

  Study JGAS000416

• Non-invasive human skin transcriptome analysis using mRNA in skin surface lipids

  Non-invasive acquisition of mRNA data from the skin can be extremely useful for understanding skin physiology and diseases. Inspired by the holocrine process, in which the sebaceous glands secrete cell contents into the sebum, we focused on the possible presence of mRNAs in skin surface lipids (SSLs). We found that measurable levels of human mRNAs exist in SSLs, where the sebum protects them from degradation by RNases. The AmpliSeq transcriptome analysis was modified to measure SSL-RNA levels, and our results revealed that the SSL-RNAs predominantly comprised mRNAs derived from sebaceous glands, the epidermis, and hair follicles. Analysis of SSL-RNAs non-invasively collected from patients with atopic dermatitis revealed significantly increased expression of inflammation-related genes and decreased expression of terminal-differentiation���related genes, consistent with the results of previous reports. Further, we found that lipid-synthesis���related genes were downregulated in the sebaceous glands of patients with atopic dermatitis. These results indicate that the analysis of SSL-RNAs is a promising strategy to understand the pathophysiology of skin diseases.

  Study JGAS000418

• Non-invasive human skin transcriptome analysis using mRNA in skin surface lipids

  Non-invasive acquisition of mRNA data from the skin can be extremely useful for understanding skin physiology and diseases. Inspired by the holocrine process, in which the sebaceous glands secrete cell contents into the sebum, we focused on the possible presence of mRNAs in skin surface lipids (SSLs). We found that measurable levels of human mRNAs exist in SSLs, where the sebum protects them from degradation by RNases. The AmpliSeq transcriptome analysis was modified to measure SSL-RNA levels, and our results revealed that the SSL-RNAs predominantly comprised mRNAs derived from sebaceous glands, the epidermis, and hair follicles. Analysis of SSL-RNAs non-invasively collected from patients with atopic dermatitis revealed significantly increased expression of inflammation-related genes and decreased expression of terminal-differentiation���related genes, consistent with the results of previous reports. Further, we found that lipid-synthesis���related genes were downregulated in the sebaceous glands of patients with atopic dermatitis. These results indicate that the analysis of SSL-RNAs is a promising strategy to understand the pathophysiology of skin diseases.

  Study JGAS000417

• RNA Splicing Dysregulation in the Pathogenesis of Chronic Lymphocytic Leukemia

  RNA splicing dysregulation is a hallmark of cancers, promoting the onset and progression of disease. In chronic lymphocytic leukemia (CLL), spliceosome mutations leading to aberrant splicing occurs in approximately 20% of patients. However, the underlying mechanism for splicing defects in spliceosome unmutated CLL cases remains elusive. To discover posttranscriptional regulation of RNA splicing, we performed RNA sequencing using RNA derived from B cells from 6 healthy donors and 36 CLL patients, along with MAZTER sequencing from 9 CLL patients (8 matched with RNA sequencing cohort) and B cells from 5 healthy donors. We found that CLL cells have dysregulated m6A modification sites on transcripts from splicing factors, suggesting a critical role of m6A modification in RNA splicing dysregulation.

  Study phs003191

• Single-cell RNA sequencing of 16 NPM1 mutated AML patients

  NPM1 mutated AML is the largest class in WHO classification, however several subtypes within NPM1 were already reported. Here, we sequence 16 NPM1 mutated AML samples with single-cell RNA-sequencing and multi-color flow cytometry from three major NPM1 subtypes we previously identified, totaling more than half a million cells. We show that the differences among three NPM1 subtypes are mainly driven by cell composition, and these differences are also reflected at cell surface protein level. With the re-analysis of CITE-seq data from another cohort and single cell variant calling on our data, we also report two distinct stem cell phenotypes: one with leukemic (CD34dimCD38-CD45RA+) and another with pre-leukemic (CD34+CD38-CD45RA-) origin. We believe that our data and findings provide novel insights regarding the etiology of NPM1 mutated AML.

  Study EGAS50000000332

• Single cell RNA sequencing of human umbilical cord blood lymphoid progenitors

  We performed single cell RNA sequencing of human umbilical cord blood. To explore the differentiation pathway for human lymphoid lineage deeply, our target cells contain CD34+CD38+CD45RA+CD19-CD7-CD10+ cells (CD10SP). All these populations are evaluated by single cell RNA sequencing.

  Study JGAS000551

• RaScALL: Rapid (Ra) screening (Sc) of RNA-seq data for prognostically significant genomic alterations in acute lymphoblastic leukaemia (ALL)

  RNA-sequencing (RNA-seq) efforts in acute lymphoblastic leukaemia (ALL) have identified numerous prognostically significant genomic alterations which can guide diagnostic risk stratification and treatment choices when detected early. However, a full RNA-seq Bioinformatics workflow is time-consuming and costly in a clinical setting where rapid detection and accurate reporting of clinically relevant alterations are essential. To accelerate the identification of ALL-specific alterations (including gene fusions, single nucleotide variants and focal gene deletions), we developed the rapid screening tool RaScALL, capable of identifying more than 100 prognostically significant lesions directly from raw sequencing reads. RaScALL uses the k-mer based targeted detection tool km and known ALL variant information to achieve a high degree of accuracy for reporting subtype defining genomic alterations compared to standard alignment-based pipelines. Gene fusions, including difficult to detect fusions involving EPOR and DUX4, were accurately identified in 98% (164 samples) of reported cases in a 180-patient Australian study cohort and 95% (n=63) of samples in a North American validation cohort. Pathogenic sequence variants were correctly identified in 75% of tested samples, including all cases involving subtype defining variants PAX5 p.P80R (n=12) and IKZF1 p.N159Y (n=4). Accurate detection of intragenic IKZF1 deletions resulting in aberrant transcript isoforms was also detectable with 98% accuracy. Importantly, the median analysis time for detection of all targeted alterations averaged 22 minutes per sample, significantly shorter than standard alignment-based approaches, ensuring accelerated risk-stratification and therapeutic triage.

  Dataset EGAD00001009087

• Evolutionary Analysis of Chronic Lymphocytic Leukemia Cells During Relapse After Allogeneic Hematopoietic Stem Cell Transplant

  We investigated the molecular dynamics driving relapse of chronic lymphocytic leukemia (CLL) following allogeneic hematopoietic stem cell transplant (allo-HSCT) through an integrated analysis of whole exome, bulk transcriptome, bulk methylome and single cell transcriptional data from paired leukemic samples representing 19 patients. We found that their clinical kinetics corresponded to distinct genetic and epigenetic evolutionary trajectories and suggest that the selection pressures of the post-transplant, immunologic bottleneck are distinct from those imposed by chemotherapy.In order to discover cancer antigens derived from annotated and unannotated protein-coding regions of the genome, we carried out ribosome profiling (Ribo-seq) and RNA-sequencing on CLL samples and isolated primary B cells from healthy donors. We discovered novel or unannotated open reading frames (nuORFs), their expression levels, as well as somatic mutations within them to predict potential neoantigens.

  Study phs001998

• Identification and characterization of tertiary lymphoid structures in brain metastases

  Brain metastases (BrM) are the most common cancers in the brain. We performed transcriptome-wide gene expression profiling combined with spatial immune cell profiling to characterize the tumor immune microenvironment in BrM from different primary tumors. We found that BrM from lung carcinoma and malignant melanoma showed overall higher immune cell infiltration as compared to BrM from breast carcinoma. RNA sequencing-based immune cell deconvolution revealed gene expression signatures indicative of tertiary lymphoid structures (TLS) in subsets of BrM from lung cancer and melanoma. This finding was corroborated by multiplex immunofluorescence staining of immune cells in BrM tissue sections. Detection of TLS signatures was associated with prolonged survival after BrM diagnosis in lung cancer patients. Our findings highlight the cellular diversity of the tumor immune microenvironment in BrM of different cancer types and suggest a role of TLS formation for BrM patient outcome.

  Study EGAS50000000563

• NGS data of human NES cells and tumors

  Raw RNA-seq data for WT and 2 Gorlin NES cells, tumors derived from MYCN mis-expressed WT NES cells, tumors derived from Gorlin NES cells, and tumors derived from Gorlin NES cells transduced with mutant DDX3X (R351W and R534S) and CRISPR/Cas9 targeting GSE1 (each sample has 3 replicates/tumors except Gorlin NES cell tumors have 4). Raw whole exome sequencing data for WT and Gorlin 1 NES cells, tumors derived from MYCN mis-expressed WT NES cells, and tumors derived from Gorlin NES cells (each sample has 3 replicates/tumors except Gorlin NES cell tumors have 4). Raw data for amplicon sequencing of GSE1 and KDM3B at regions targeted by CRISPR/Cas9 in Gorlin NES cells.

  Dataset EGAD00001004990

• Deciphering molecular mechanisms underlying hematological malignancies and development of novel therapeutic approaches

  We aim to identify epigenomic features dysregulated in hematological malignancies through epigenetic analyses of hematological malignant cells. We also perform RNA sequencing to profile tumor cell-specific transcriptomes and target gene sequencing to profile somatic gene mutations in tumor cells. Regarding identified epigenomic abnormalities, we perform further analysis to determine whether they could be good candidates to translate into therapy development. To this end, we will modulate the activity of targets by using their activators and inhibitors in vitro and establish xenograft mouse models of hematological malignancies and manipulate their activity in vivo. Through these studies, we aim to develop new therapeutic agents or modalities that lead to improved patients��� prognosis.

  Study JGAS000603

• 'KOREAN' never-smoker female adenocarcinoma RNA-seq

  Multi-layered genomic studies such as the TCGA project have greatly advanced our understanding on molecular pathogenesis of lung cancer. For Asian nonsmoker patients, however, majority of studies have been limited to mutational analyses, emphasizing ethnic differences in driver mutations (e.g. more frequent EGFR mutations and ALK fusions). In essence, a comprehensive multi-layered characterization that could lead to molecular etiology and patient stratification scheme to be translated into clinical applications for this patient group is still missing. Here we report molecular profiling of tumor and matched normal tissues from 114 non-small-cell lung adenocarcinoma patients using whole exome sequencing, transcriptome sequencing, and array comparative genomic hybridization (CGH).

  Study EGAS00001003789

• Raw RNA sequencing of hepatoblastoma PDX cell line HB-303-LEF

  Raw RNA sequencing of hepatoblastoma PDX cell line HB-303-LEF

  Study EGAS50000000928

• Characterization of Human Transcriptome by Computational and HTS Approaches

  We have deeply sequenced total RNA and whole exome of six different post-mortem human snap-frozen tissues (brain, liver, lung, striated muscle, kidney, heart) from three unrelated healthy Caucasian individuals (males, aged 47-54) with the aim to characterize post-transcriptional events due to alternative splicing and RNA editing. In addition, to facilitate the detection of RNA editing sites we have also resequenced the entire genome of each individual. Data are also used to investigate tissue-specific abundance of mitochondrial DNA from exomes and its correlation with mitochondrial transcription, mass and respiratory activity. Tissues were obtained from Cureline (South San Francisco, CA, USA). DNA and RNA were purified using the DNeasy Blood and Tissue Kit (Qiagen, Hilden, Germany) and the RNeasy Plus Mini Kit (Qiagen, Hilden, Germany), respectively. Exome capture was performed using the TruSeq Exome Enrichment Kit (Illumina, San Diego, CA) and the sequencing was carried out at IGA Technology Services in Udine (Italy) on Illumina HiSeq 2000 (generating for each tissue approximately 40 millions of 100bp paired-end reads). Strand-oriented RNA reads (2x100bp) were generated using the TruSeq Stranded Total RNA Sample Prep Kit (Illumina, San Diego, CA, USA) and sequenced at IGA Technology Services in Udine (Italy) on Illumina HiSeq 2000 platform. Whole genome resequencing was performed at Personal Genomics in Italy on an Illumina HiSeq 2000 platform (2x100bp) with a mean coverage of 30X. MiRNA-Seq was instead performed at IBBE Institute (Italy) using the TruSeq Small RNA Sample Prep Kit on Illumina MiSeq platform. Preliminary bioinformatics analyses have been performed to check quality using FASTQC software and inconsistent read regions have been trimmed using trim_galore. All reads were mapped onto the human reference genome (version hg19) using GSNAP.

  Study phs000870

• Identification of the Global miR-130a Targetome Reveals a Novel Role for TBL1XR1 in Hematopoietic Stem Cell Self-Renewal and t(8;21) AML

  In this study, we identified miR-130a as a regulator of HSC self-renewal and differentiation. To characterize gene expression changes following enforced expression of miR-130a OE, we performed RNA-seq in CD34+ cord blood (CB) cells transduced with control and miR-130a OE lentiviruses. To capture miRNA targets in an unbiased, transcriptome-wide manner, we perfomed enhanced CLIPseq procol in 2 replicates of CD34+ CB cells and Kasumi-1 cell line, which represent a model system for t(8;21) AML. We chose this cell line, as we found miR-130a to be highly expressed in this AML subtype where it is critical for maintaining the oncogenic molecular program mediated by AML1-ETO. Chimeric Ago2 eCLIPseq in CD34+ CB cells combined with Mass Spectrometry data analysis identified TBL1XR1 as a principal target of miR-130a. To elucidate gene expression changes associated with TBL1XR1 loss of function, we performed RNA-seq in CD34+CD38- CB cells transduced with control and shRNA targeted against TBL1XR1. To determine the functional significance of high miR-130a expression levels in Kasumi-1 cells on the molecular network controlled by AML1-ETO, we performed CUT&amp;RUN assay and RNA-seq in Kasumi-1 cells following miR-130a knock-down (KD). Collectively, our findings reveal a unique role of miR-130a in regulating normal hematopoietic stem cell self-renewal and how elevated levels of miR-130a in t(8;21) AML contribute to the leukemogenesis of this AML subtype.

  Dataset EGAD00001008412

• Global RNA sequencing data of human iPSC-derived microglia from frontotemporal dementia (FTD) patients

  Global RNA sequencing was performed in RNA samples extracted from human iPSC-derived microglia from healthy controls and sporadic (non-genetic) and genetic C9orf72 hexanucleotide repeat expansion-carrying patients with FTD.

  Study EGAS50000001688

• Single-cell spatiotranscriptomic dissection of ex vivo human heart right atrial appendage and pericardial fluid in ischemic heart disease and heart failure

  We use cardiac and pericardial fluid biopsies collected during open-heart surgery in control, ischemic heart disease, heart failure, and myocardial infarction context. For each sample, single-nuclei RNA sequencing experiment is performed. We also perform spatial transcriptomics on the heart samples. We annotate the cells in major cell types, in addition to subtypes annotation of vascular and immune cells. The disease annotation enables us to reveal substantial differences in gene expression at the cell subpopulation levels. Our results demonstrate the importance of high-resolution cellular type/state mapping in the elucidation of human cardiovascular disease pathogenesis.

  Study EGAS50000000653

• RNAseq data to study PRPF6 regulated splice forms in colon cancer cell lines

  Alternative splicing plays critical roles in differentiation, development, and cancer (Pettigrew et al., 2008; Chen and Manley, 2009). The recent identification of specific spliceosome inhibitors has generated interest in the therapeutic potential of targeting this cellular process (van Alphen et al., 2009). Using an integrated genomic approach, we have identified PRPF6, an RNA binding component of the pre-mRNA spliceosome, as an essential driver of oncogenesis in colon cancer. Importantly, PRPF6 is both amplified and overexpressed in colon cancer, and only colon cancer cells with high PRPF6 levels are sensitive to its loss. Our data clearly point to an important role for PRPF6 in colon cancer growth and suggest that a better understanding of its role in alternative splicing in colon cancer is warranted. To determine the specific alternative splice forms that PRPF6 regulates in colon cancer, we plan three experiments: 1. The first involves knocking down expression of PRPF6 in two different cancer cell lines with 3 different siRNAs, and then completing RNA-seq to determine the gene expression changes that occur relative to a non-targeting control siRNA. Because of the role for PRPF6 in pre-mRNA splicing, we especially want to quantify the changes in splice-specific forms of all genes genome-wide to identify genes whose splicing is altered upon PRPF6 knockdown. 2. The second involves immunoprecipitating PRPF6 from two different cancer cell lines and isolating any RNA that is bound to PRPF6, since PRPF6 is an RNA-binding protein. We then want to carry out RNA-seq to identify which RNA molecules co-immunoprecipitated with PRPF6. This will help us determine possible functions for PRPF6 in regulating colon cancer growth. 3. The third involves overexpressing PRPF6 in cell lines and then carrying out RNA-seq to identify any changes in splice-specific gene expression. This will allow us to determine whether increased PRPF6 expression is sufficient to drive alternative splicing changes.

  Dataset EGAD00001000817

• RNA sequencing of 12 NSCLC samples from 4 patients at MDACC

  Multi-region RNA sequencing of 12 NSCLC samples from 4 patients at MDACC

  Study EGAS00001005951

• Single cell RNA sequencing of human cord Blood CD34 Cells

  We performed single cell RNA sequencing and ATAC e valuation of human umbilical cord blood. To explore the differentiation pathway for human lymphoid lineage, our target cells contain CD34-positive cord blood. That population is evaluated by single cell RNA sequencing and single cell ATAC.

  Study JGAS000528

• Dataset for melanoma-RNA

  Rare cancer sequencing data of 49 runs in tumor/control pairs, which were uploaded to umbrella studies. The sequencing was always paired

  Dataset EGAD00001008858

• Dataset for gynecologic_cancer-RNA

  Rare cancer sequencing data of 48 runs in tumor/control pairs, which were uploaded to umbrella studies. The sequencing was always paired

  Dataset EGAD00001008856

• Dataset for hematopoietic_malignancy-RNA

  Rare cancer sequencing data of 47 runs in tumor/control pairs, which were uploaded to umbrella studies. The sequencing was always paired

  Dataset EGAD00001008860

• Integrated clinical, whole genome, and transcriptome analysis of multisampled lethal metastatic prostate cancer

  We report the first combined analysis of whole genome sequence, detailed clinical history, and transcriptome sequence of multiple prostate cancer metastases in a single patient (A21). Whole genome and transcriptome sequence was obtained from 9 anatomically separate metastases, and targeted DNA sequencing was performed in cancerous and noncancerous foci within the primary tumor specimen removed 5 years prior to death. Transcriptome analysis revealed increased expression of AR-regulated genes in liver metastases that harbored an AR p.L702H mutation, suggesting a dominant effect by the mutation despite being present in only 1 of an estimated 16 copies per cell. The metastases harbored several alterations to the PI3K/AKT pathway, including a clonal truncal mutation in PIK3CG and present in all metastatic sites studied. The list of truncal genomic alterations shared by all metastases included homozygous deletion of TP53, hemizygous deletion of RB1 and CHD1, and amplification of FGFR1. If the patient were treated today given this knowledge, use of second-generation androgen-directed therapies, cessation of glucocorticoid administration, and therapeutic inhibition of the PI3K/AKT pathway or FGFR1 receptor could provide personalized benefit. Three previously unreported truncal clonal missense mutations (ABCC4 p.R891L, ALDH9A1 p.W89R, and ASNA1 p.P75R) were expressed at the RNA level and assessed as druggable. The truncal status of mutations is critical for actionability, and can only be determined through analysis of multiple sites of metastasis. Our findings suggest that a large set of deeply analyzed cases could serve as powerful guide to more effective prostate cancer basic science and personalized cancer medicine clinical trials.

  Study EGAS00001001659

• Effect of the Placental Transcriptome on Stunting in a Longitudinal African Cohort

  Mammals with placentas and flowering plants evolved genomic imprinting in nutritive tissues, the placenta and endosperm, respectively. In these tissues, the genomes inherited from the mother and father are in conflict over resource allocation to offspring. In imprinted genes, transcription is repressed on the paternal or the maternal allele, resulting in allele specific expression (ASE). We investigated the variation in ASE of imprinted genes in term human placentas in order to detect loss of imprinting (LOI), which leads to partial expression of the repressed allele. We collected the placental tissue from birth to women in our multigenerational, prospective cohort study in Mali, West Africa. We followed the women from their own infancies, early childhood to adulthood (age 18+ years). Contingent on prior informed consent, we collected placental tissue and umbilical cord tissue. We conducted RNA-Seq of the fetal compartment of the placentas and targeted DNA-Seq of the umbilical cord tissue, which is fetal, and of saliva samples from parents. Our sequencing effort produced two datasets. The first dataset is the whole transcriptome RNA-Seq dataset of 111 biopsies (59 placentas) and genotyping of 96 genes. Birth length, weight, and placental weight for the children associated with this dataset are listed in the phenotype file (DOI: 10.1093/molbev/msz226). The second dataset includes targeted RNA-Seq of 262 samples (251 placentas) and targeted DNA-Seq for 766 genes. The genes were selected because they met any one of the following criteria: (1) imprinted and reported in some studies, (2) highly expressed in placenta, or (3) relevant to diseases of interest in this cohort (https://doi.org/10.1093/g3journal/jkab176). This study provides the first systematic analysis of variation in LOI across genes and individuals in a human population, and should shed light on the hypothesis that the modulation of imprinting is an epigenetic mechanism and plays a role in the regulation of offspring growth.

  Study phs001782