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• Characterisation of the genetic landscape of cutaneous leiomyoma and leiomyosarcoma - Leiomyosarcoma RNA

  Cutaneous leiomyoma (cLM) and leiomyosarcoma (cLMS) are rare benign and malignant soft tissue neoplasms showing smooth muscle differentiation, respectively, that arise from mesenchymal cells in the dermis and subcutis. Through whole exome sequencing of cLM and cLMS cases, we observed distinct differences between the somatic mutational profile of these tumour types. FH was identified as a driver gene in cLM with genetic alterations of FH occurring via somatic point mutation, somatic copy number loss, biallelic inactivation and germline point mutations. TP53 and RB1 were identified as driver genes in the cLMS cohort, with genetic alterations of TP53 occurring via somatic and germline point mutations, copy number loss and biallelic inactivation. Using RNA-sequencing, we identified recurrent gene fusions, including CRTC1/3-MAML2 in cLMS and a novel MYLK-MAP3K2 fusion. Analysis of the cell types present in the tumour microenvironment revealed a significantly increased presence of macrophages and decreased presence of myeloid dendritic cells in the cLMS cohort relative to the cLM cohort. Additionally, we identified common driver genes between cLMS and LMS from other sites. Thus, we provide the first in-depth profile of the genetic landscape of cLM and cLMS.

  Dataset EGAD00001014790

• STARR-seq of ERa binding sites in MCF7 and Ishikawa cell lines

  A oligo-captured STARR-seq library was generated using as targets ERa binding regions indetified by ChIP-seq in Ishikawa (Endometrial cancer) and T47D (breast cancer) cell lines and, breast cancer primary tissues. STARR-seq assays have been performed in MCF-7 and Ishikawa cell lines. Cells have been cultured for 3 days in hormone deprivated (phenol-red free) media and stimulated for 6 hours by 10nM estradiol (E2) or DMSO (negative control).

  Dataset EGAD50000000015

• Genomic and transcriptomic analysis of thymic epithelial tumors

  Thymic epithelial tumors (TETs), comprising various histologic types of thymomas and thymic carcinomas, originate from thymic epithelial cells. Each histologic type is typically associated with a distinct immune cell composition and clinical manifestation. A better understanding of the cellular origins and molecular pathways underlying this heterogeneity is needed to improve patient stratification and treatment. Here, we conducted an integrated genomic and transcriptomic analysis of 124 thymomas and 13 thymic carcinomas, including 20 newly sequenced cases combined with 117 cases from publicly available datasets. This approach stratified TETs into three subgroups with different possible origins: GTF2I-mutant (GTF2I-type) thymomas, copy number-altered (CN-type) thymomas, and thymic carcinomas.

  Study EGAS00001004227

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

  Patients with amyotrophic lateral sclerosis (ALS), a rare fatal neurodegenerative disease, face a lengthy diagnostic process, and, although most survive only 2 to 4 years from diagnosis, lack information regarding their specific anticipated disease course due to a lack of prognostic tools. Although ALS is a heterogeneous disease of varied etiology, peripheral immune system dysfunction is ubiquitous, reflected in altered whole blood transcriptome. Herein, we profiled whole blood gene expression by RNA sequencing in a large cohort of ALS cases versus controls. Several machine learning classifiers trained on our gene expression dataset predicted case-control status and survival, and integration analysis with external cohorts led to the identification of drug candidates.

  Study EGAS50000001019

• H3Africa EPIGEN EWAS

  Data from 59 whole blood samples from pregnant mothers, unexposed and exposed to the Rwandan genocide, was generated using Infinium MethylationEPIC BeadChip Kit.

  Dataset EGAD00010002383

• Ovarian cancer cfDNA dataset

  The dataset contains 23 ovarian cancer and 2 healthy control urine cfDNA samples. Shallow WGS was performed on an Illumina Novaseq S4 PE150bp. Samples are provided as raw reads without any prior processing.

  Dataset EGAD00001010848

• Phase 1/2 Study of the Indoleamine 2,3-Dioxygenase 1 Inhibitor Linrodostat Mesylate Combined With Nivolumab or Nivolumab and Ipilimumab in Advanced Solid Tumors or Hematologic Malignancies

  Purpose: To evaluate the safety, efficacy, pharmacokinetics, pharmacodynamics, and biomarker data of linrodostat mesylate, a selective, oral indoleamine 2,3-dioxygenase 1 (IDO1) inhibitor, combined with nivolumab ± ipilimumab in advanced solid tumors and hematologic malignancies. Patients and Methods: In this phase 1/2 study, patients received once-daily (QD) linrodostat (part 1 [escalation], 25-400 mg; part 2 [expansion], 100 or 200 mg) plus nivolumab (480 mg every [Q] 4 weeks [W] or 240 mg Q2W) or triplet therapy (part 3, linrodostat 20-100 mg QD; nivolumab 360 mg Q3W or 480 mg Q4W; ipilimumab 1 mg/kg Q6W or Q8W). Endpoints included safety and efficacy (co-primary; parts 2, 3), pharmacokinetics, pharmacodynamics, biomarkers, and efficacy (part 1). Results: Fifty-five, 494, and 41 patients were enrolled in parts 1, 2, and 3, respectively. Linrodostat exposures exceeded predicted therapeutic target concentrations starting at 50 mg. Rates of grade 3/4 adverse events were 50.1%-63.4%. The maximum tolerated linrodostat dose was 200 mg; dose-limiting toxicities were primarily immune related. Responses were observed across different cohorts, study parts, and tumor types, particularly in immunotherapy-naive patients. Kynurenine decreased with linrodostat + nivolumab, regardless of response. In contrast, interferon gamma (IFN-γ) gene expression signature was associated with response; in nonmelanoma patients, a composite of low tryptophan 2,3-dioxygenase (TDO2) gene expression plus high IFN-γ signature was associated with response. Conclusions: Linrodostat + nivolumab ± ipilimumab demonstrated a manageable safety profile. Kynurenine changes supported IDO1 pathway inhibition but did not correlate with response. A composite biomarker of low TDO2 expression plus high IFN-γ gene expression may predict response to linrodostat + nivolumab.

  Study EGAS50000000710

• Single-cell transcriptomic data from tumor samples

  Extramedullary multiple myeloma is an aggressive form of multiple myeloma where the myeloma cells escape BM microenvironment and infiltrate distant tissues.We analyse using single cell techniques, the composition and functional state of major immune cells in EMM tumor microenvironment, T and NK cells. This dataset contains the singlecell RNAseq data used in the publication. It includes scRNAseq data from tumor samples across extramedullary multiple myeloma soft tissue (EMM) (n=5; 3 additional samples in the study are under accession numbers mentioned in the publication), EMM bone marrow (EMM_BM) (n=5), and relapsed/refractory multiple myeloma (RRMM_BM) BM (n=6).

  Study EGAS50000001038

• Integrated Transcriptomic and Regulatory RNA Profiling Reflects Complex Pathophysiology and Uncovers a Conserved Gene Signature in End Stage Heart Failure RNA-Seq data

  Heart failure (HF) is a complex syndrome. Despite availability of multiple treatment options, the mortality remains high and the quality of life poor. Better understanding of the underlying pathophysiological processes can lead to development of novel therapies. Multiple comparative transcriptomics studies, which revealed gene level changes in the key pathophysiological pathways in failing hearts, point towards heterogeneity from interplay of disease stage, etiologies and ethnicity. Transcriptomic characterization of HF in patients from different ethnicities can potentially help in understanding the heterogeneity imparted by various factors and the core elements in heart failure.

  Study EGAS50000000810

• Intercepting Progression from Pre-Invasive to Invasive Lung Adenocarcinoma

  An improved understanding of the biology of lung cancer is needed to intercept the disease at an early point in its progression. In this project we have used multidimensional methods to profile the tumor microenvironment (TME) and to determine the crosstalk between cancer cells and the TME in pre-invasive to invasive human lung non-solid adenocarcinomas. Comparative analysis of the cellular and molecular events associated with the distinct histological stages will lead to identification of the critical events triggering progression and thereby identify targets to intercept disease progression. The data being submitted represents the genomic profiles of patient samples with pre-invasive and invasive human lung adenocarcinomas.

  Study phs002818

• RNA-sequencing of T-cell Acute Lymphoblastic Leukemia (T-ALL)

  This dataset contains raw fastq files from the RNA-Seq of 96 T-Acute Lymphoblastic Leukemia. Libraries where prepared using Agilent SureSelect XT-HS2 RNA Reagent Kit. As such, reads contain molecular barcodes that could be specifically handled using the AGeNT tool.

  Dataset EGAD00001010273

• Epigenome maps of time-resolved monocyte to macrophage differentiation and innate immune memory

  Innate immune memory is the phenomenon whereby innate immune cells such as monocytes or macrophages undergo functional reprogramming after exposure to microbial components such as LPS. We apply an integrated epigenomic approach to characterize the molecular events involved in LPS-induced tolerance in a time dependent manner. ChIP-seq, RNA-seq, WGBS and ATAC-seq data were generated. This analysis identified epigenetic programs in tolerance and trained macrophages, and the potential transcription factors involved. Experimental set-up Time-course in vitro culture of human monocytes. Two innate immune memory states can be induced in culture through an initial exposure of primary human monocytes to either LPS or BG for 24 hours, followed by removal of stimulus and differentiation to macrophages for an additional 5 days. Cells were collected at baseline (day 0), 1 hour, 4 hour, 24 hour and 6 days.

  Dataset EGAD00001002693

• Metabolic and molecular consequences of the TBC1D4 p.Arg684Ter variant in human skeletal muscle

  Skeletal muscle of Inuit homozygous carriers of the common Greenlandic TBC1D4 p.Arg684Ter variant is severely insulin resistant but have normal metabolic responses during exercise

  Dataset EGAD50000000059

• FFPE CRC WGS Data

  The data consists of 3 BAM files. Two of three BAMs are tumour FFPE samples (1 repaired-FFPE; 1 unrepaired-FFPE); The other BAM file is sequenced from normal colon tissue

  Dataset EGAD00001007716

• single cell RNA-seq data of 10 small cell lung cancer patients

  This dataset contains 10 paired fastq files sequenced on Illumina NextSeq 550 sequencer. Tumors were rapidly dissociated after the surgical procedure using the Miltenyi Biotec Human Tumor Dissociation kit (cat# 130-095-929). Libraries were constructed using the VDJ NextGEM v1.1 10x Genomics Chromium kit. Single cell RNA-seq analysis was performed using Seurat R package.

  Dataset EGAD50000002034

• RNA-Seq Profiles from CA017-003 Clinical Trial

  The dataset contains RNAseq profiles of 182 patients from the CA017-003 clinical trial. The Allprep DNA/RNA FFPE kit was used to simultaneously purify genomic DNA and total RNA from formalin-fixed, paraffin embedded (FFPE) tissue sections. RNAseq libraries (50PE, 50M) were constructed using Illumina TruSeq RNA Access method. Fastq files are included.

  Dataset EGAD50000000991

• RNA Transcriptomic and DNA Methylation Landscape in FTLD-TDP and Controls

  Frontotemporal lobar degeneration (FTLD) is one of the leading causes of dementia in individuals younger than 65 years, with the aggregation of TDP-43 as one of the most common forms of FTLD. FTLD-TDP is clinically, genetically and pathologically heterogeneous, with GRN and C9orf72 as the most common genetic forms (although more than 50% of the cases are genetically unexplained), and A, B and C as the most common pathological subtypes. To investigate the molecular differences between the different forms of FTLD-TDP, we performed bulk RNA sequencing (RNAseq) and reduced representation bisulfite sequencing (RRBS) from different brain regions of FTLD-TDP patients and controls. The RNAseq dataset includes samples from the frontal cortex of 149 individuals, comprising 127 FTLD-TDP cases (genetically unexplained types A (27), B (20) and C (22), 24 GRN mutation carriers, and 34 C9orf72 expansion carriers) and 22 controls. The RRBS dataset includes samples from the frontal cortex of 158 individuals —119 FTLD-TDP cases (genetically unexplained types A (25), B (24), and C (25), 20 GRN mutation carriers, and 25 C9orf72 expansion carriers) and 39 controls; and from the cerebellum of 151 individuals —113 FTLD-TDP cases (genetically unexplained types A (24), B (21), and C (23), 20 GRN mutation carriers, and 25 C9orf72 expansion carriers) and 38 controls. In total, the study consists of data from 183 unique individuals, with some overlap across the different datasets.

  Study phs004075

• Small cell carcinoma of the ovary, hypercalcemic type, displays frequent inactivating germline and somatic mutations in SMARCA4

  Small cell carcinoma of the ovary of hypercalcemic type (SCCOHT) is an extremely rare, aggressive cancer affecting children and young women. We identified germline and somatic inactivating mutations in the SWI/SNF chromatin-remodeling gene SMARCA4 in 75% (9/12) of SCCOHT patients in addition to SMARCA4 protein loss in 82% (14/17) of SCCOHT tumors, but in only 0.4% (2/485) of other primary ovarian tumors. These data implicate SMARCA4 in SCCOHT oncogenesis.

  Study EGAS00001000714

• RNAseq profiles from the CheckMate-142 clinical trial

  The dataset contains RNAseq profiles of 57 patients from the CheckMate-142 clinical trial. The Allprep DNA/RNA FFPE kit was used to simultaneously purify genomic DNA and RNA from formalin-fixed, paraffin embedded (FFPE) tissue sections. Baseline tumor tissue samples were processed using the Illumina TruSeq RNA Access in-solution hybrid capture panel and underwent subsequent NGS on the Illumina NovaSeq platform. Fastq files are included.

  Dataset EGAD50000000609

• TCR Repertoire Sequencing to Evaluate the Diversity of Follicular Helper T Cells in HIV Infected Lymph Nodes

  The TCR repertoire of CD4+ T cells in human lymph nodes is a case-based analysis of the TCR repertoire of CD4+ T cells in human lymph nodes. The study aims to determine how HIV infection alters the repertoire complexity of follicular helper T cells (TFH) in relationship to other T cell subsets in the lymphoid compartment. This study performs TCR repertoire sequencing using Molecular Identifier Clustering-based Immune Repertoire Sequencing (MIDCIRS). We found TFH cells become clonally expanded and convergently selected in LNs from patients with chronic HIV infection.

  Study phs001548

• Whole genome bisulfite sequencing of prostate cancer samples upon oral pimonidazole administration

  Whole genome bisulfite sequencing was performed using laser-capture of microdissected specimen sections comparing PIMO positive and negative carcinoma areas. A hypoxia related methylation molecular signature was generated.

  Study EGAS50000000069

• Small molecule screen reveals synergy of cell cycle checkpoint kinase inhibitors with DNA-damaging chemotherapies in medulloblastoma (methylation dataset)

  human medulloblastoma xenograft isolated from mouse brain was frozen and genomic DNA or RNA was extracted. Bisulfite converted DNA was processed and hybridised to illumina EPIC or 450K arrays using standard protocols. RNAseq was performed on total RNA.

  Dataset EGAD00001006583

• SEQCAP_Internation_1q_Type_2_Consortium - Agilent SureSelec

  The aim of this project is to identify rare variants in the 1q region associated with type 2 diabetes. To this end 651 case samples and 651 control samples from six populations have been pooled (pool sizes range from 27-33 individuals), and are being sequenced. The hybridization solution being used captures the exons and UTRs of genes in the 1q region.

  Dataset EGAD00001000421

• T cell receptors of pathogenic CD4 T cells isolated by using distinct phenotypic markers in celiac disease

  The dataset contains rearranged TCR‐α and TCR‐β genes of Ttet+/Tpat+, Ttet-/Tpat+ and Ttet-/Tpat- CD4+ cells from gut biopsies (exvivo) or that of T cell clones generated from gut biopsies (invitro) from 12 CeD patients.

  Dataset EGAD00001008098

• HiC-sequencing in human monocyte differentiation

  This dataset consists of in situ HiC-seq data from human monocytes, monocyte-derived dendritic cells as well as monocyte-derived cells that were subjected to siRNA treatment targeting CTCF or RAD21. In total, the data set includes 42 samples.

  Dataset EGAD00001007955