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• Whole-exome ultra-high throughput sequencing in brain samples of suicide victims who had suffered from major depressive disorder and control subjects who had died from other causes

  We carried out whole-exome ultra-high throughput sequencing in brain samples of suicide victims who had suffered from major depressive disorder and control subjects who had died from other causes. This study aimed to reveal the selective accumulation of rare variants in the coding and the UTR sequences within the genes of suicide victims. We also analysed the potential effect of STR and CNV variations, as well as the infection of the brain with neurovirulent viruses in this behavioural disorder. As a result, we have identified several candidate genes, among others three calcium channel genes that may potentially contribute to completed suicide. We also explored the potential implication of the TGF-β signalling pathway in the pathogenesis of suicidal behaviour. To our best knowledge, this is the first study that uses whole-exome sequencing for the investigation of suicide.

  Study EGAS00001002818

• Whole-exome ultra-high throughput sequencing in brain samples of suicide victims who had suffered from major depressive disorder and control subjects who had died from other causes.

  We carried out whole-exome ultra-high throughput sequencing in brain samples of suicide victims who had suffered from major depressive disorder and control subjects who had died from other causes. This study aimed to reveal the selective accumulation of rare variants in the coding and the UTR sequences within the genes of suicide victims. We also analysed the potential effect of STR and CNV variations, as well as the infection of the brain with neurovirulent viruses in this behavioural disorder. As a result, we have identified several candidate genes, among others three calcium channel genes that may potentially contribute to completed suicide. We also explored the potential implication of the TGF-β signalling pathway in the pathogenesis of suicidal behaviour. To our best knowledge, this is the first study that uses whole-exome sequencing for the investigation of suicide.

  Study EGAS00001003081

• POPLAR clinical data

  Relevant clinical data for POPLAR including treatment arm, histology, overall survival, progression-free survival, and best confirmed overall response.

  Dataset EGAD00001008548

• OAK clinical data

  Relevant clinical data for OAK including treatment arm, histology, overall survival, progression-free survival, and best confirmed overall response.

  Dataset EGAD00001008549

• Bleomycin Induced Pneumonitis WGS dataset

  This is whole genome sequencing data from a cohort of 18 patients with germ cell tumours or Hodgkin Lymphoma, who developed clinically significant bleomycin-induced pneumonitis despite low clinical risk. DNA was extracted from whole blood, and 150-base paired-end reads were generated on an Illumina NovaSeq 6000 instrument to a minimum 30x depth. Sequence reads were aligned to the GRCh38 reference with BWA MEM, and germline variants were called following GATK best practice procedures. The dataset comprises per-sample read alignment files in BAM format, and a joint-called germline variant file in VCF format.

  Dataset EGAD50000002221

• Influence of the Microbiome on Epigenetic Mechanisms in IBD

  Live CD4 T cells were sorted from inflamed and non-inflamed tissue samples of IBD patients or from healthy and IBD blood samples. ATAC-Seq libraries were generated from live CD4 T cells sorted from i) inflamed and non-inflamed tissue samples, ii) healthy and IBD blood samples, or from iii) CD4 T cell subsets polarised from healthy blood samples. After isolating crude nuclei, live CD4+ T cells were treated with Tagment DNA buffer and Tagment DNA Enzyme (Nextera DNA Library Prep Kit, Illumina), and then the DNA was purified by MinElute PCR Purification Kit (Qiagen). Transposed DNA fragments were amplified using specific adapters followed by purification with MinElute PCR Purification Kit (Qiagen). Fragments from 240-360pb were selected in the PippinHT system (Sage Science). The quality of the library and its DNA concentration were assessed by Bioanalyzer instruments (Agilent Technologies) and ultimately submitted for sequencing using Illumina HiSeq 2500 sequencer, V4 chemistry. On the other hand, single cell RNA-Seq libraries were generated exclusively from inflamed and non-inflamed tissue samples of Crohn’s disease patients. Briefly, live CD4 T cells were captured and encapsulated before cDNA amplification using the 10X Genomics Chromium Platform. Samples were prepared as outlined by 10x genomics Single Cell 3’ Reagent Kits v2 user guide. Samples were sequenced on a HiSeq 2500 with the following run parameters: Read 1 – 26 cycles, read 2 – 98 cycles, index 1 – 8 cycles.

  Dataset EGAD00001011066

• Sleep Abnormalities in Rare Genetic Disorders: Angelman Syndrome, Rett Syndrome, and Prader-Willi Syndrome

  This research study will investigate sleep behavior in the rare neurological disorders Angelman Syndrome (AS), Rett Syndrome (RTT), Prader-Willi Syndrome (PWS) and Early-onset Morbid Obesity (EMO). Sleep is very important to proper health and plays a critical role in learning, memory, brain development and brain function. Sleep disturbances can have negative effects on health and the quality of life of children and their families. Sleep disorders are common in individuals with AS, RTT, PWS and EMO. As a result, individuals with AS, RTT, PWS and EMO are at risk for sleep-related health problems that can worsen existing daytime behaviors and lead to additional problems with learning and memory. The principal objectives of the study are to: Characterize sleep behavior in individuals with Angelman Syndrome, Rett Syndrome, Prader-Willi Syndrome and Early-onset Morbid Obesity. Compare sleep behavior in these individuals with sleep behavior in normal controls Assess the natural history of sleep behavior in individuals with Angelman Syndrome, Rett Syndrome, Prader-Willi Syndrome and Early-onset Morbid Obesity About this Study This is a questionnaire study that will evaluate the sleep behavior of individuals with AS, RTT or PWS (participants), or unaffected siblings of individuals with AS, RTT or PWS (controls). Those participating in the study will already be registered with the Rare Disease Clinical Research Network (RDCRN) and have a confirmed diagnosis of AS, RTT or PWS or be an unaffected sibling. We will look at the medical records on file with the RDCRN to confirm diagnosis of AS, RTT or PWS. Study participants will participate in the study at their regularly scheduled RDCRN clinic visits. Participants will be asked to complete questionnaires at the study visits that will document their sleep behaviors. The questionnaires are not difficult and participants should be able to complete them in approximately 15-30 minutes. Parents and legal guardians are allowed to assist participants or answer on their behalf. Questionnaires will be administered at the initial study visit and at a 12 month follow-up visit to document any changes in sleep behavior. We hope to enroll approximately 1400 individuals with either AS, RTT or PWS or their unaffected siblings.

  Study phs001292

• Adaptive Therapy Exploits Fitness Deficits in Chemotherapy-Resistant Ovarian Cancer to Achieve Long-Term Tumor Control Open Access

  Drug resistance results in poor outcomes for cancer patients. Adaptive therapy is a potential strategy to address drug resistance that exploits competitive interactions between sensitive and resistant subclones. Here, we showed that adapting carboplatin dose according to tumor response (adaptive therapy) significantly prolonged survival of murine ovarian cancer models compared to standard carboplatin dosing, without increasing mean daily drug dose or toxicity. Platinum resistant ovarian cancer cells exhibited diminished fitness when drug was absent in vitro and in vivo, which caused selective decline of resistant populations due to reduced proliferation and increased apoptosis. Conversely fitter, sensitive cells re-grew when drug was withdrawn. Using a bioinformatics pipeline that exploits copy number changes to quantify the emergence of treatment resistance, analysis of cell‐free DNA obtained longitudinally from ovarian cancer patients during treatment showed subclonal selection through therapy, and measurements of resistant population growth correlated strongly with disease burden. These preclinical findings pave the way for future clinical testing of personalized adaptive therapy regimens tailored to the evolution of carboplatin resistance in individual ovarian cancer patients.

  Study EGAS50000001142

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• Circulating cell-free DNA analysis in Small Cell Lung Cancer

  Small cell lung cancer (SCLC) accounts for ~250,000 deaths worldwide each year. Acquisition of adequate tumour biopsies is challenging and liquid biopsies present the best option for patient stratification and response monitoring. We present genome-wide and targeted plasma DNA sequencing data that identifies tumour related changes in 91% of limited (LS-SCLC) and 100% of extensive stage (ES-SCLC) patients. Parallel analysis of circulating tumour cells (CTCs, by CellSearch) based on ≥ 1 CTC/7.5ml blood increased tumour detection frequencies to 98% patients (95% for LS-SCLC) where CTC count and plasma DNA readouts correlated with disease stage and overall survival (OS). Targeted plasma DNA sequencing identified potential therapeutic targets in >50% of patients. This approach will support trials of targeted therapies where improved patients outcomes are urgently required.

  Study EGAS00001003110