We sequence >1000 whole genomes from 9 patients with CML, providing the largest sequencing dataset for this cancer. We reconstruct phylogenetic trees using somatic mutations and infer BCR::ABL1 timing and tumour growth rates. We correlate mutation landscapes and clonal trajectories with clinical features.
This data contains DNA methylation data obtained from the PBMCs obtained from type 2 diabetes adolescents and controls. There are 21 diabetic samples and 10 controls. This dataset also contains metabolic data obtained from the serum of 155 samples. There are 113 diabetic and 42 control samples.
Paired whole exome sequencing data of the HIPO head and neck cancer (HNC) (n=83), using Agilent SureSelect V4+UTRs and V6+UTRs with the sequencing platforms HiSeq2000 and HiSeq2500. The reads were aligned to hg19. This is part of project H019.
4 HPS1 patient monocyte-derived macrophages and 4 controls were RNA sequenced at baseline and after Salmonella Typhimurium infection. We used paired end sequencing on an Illumina HiSeq 4000. Each sample was run on 3 lanes for sequencing depth, which we combined for our analysis.
This dataset contains the count matrices and corresponding metadata for our study on bronchial epithelial cells response to RSV in healthy and in asthma. This scRNAseq data is from primary cells, that have been differentiated in ALI cultures and infected with RSV.
RNA-Seq and ATAC-Seq of iPSC derived neurons under baseline and KCl stimulation conditions from 10 distinct donors, including 5 healthy controls and 5 schizophrenic individuals. scATAC of human post mortem prefrontal cortex from 4 adult individuals including 2 neurotypical individuals and 2 schizophrenic individuals.
We wish we perform whole genome sequencing on known clonal libraries of human oesophagus to provide a detailed investigation into differences in mutational burden, copy number and mutational signatures both within and between individuals.
Bacteriophage Immunoprecipitation Sequencing (PhIP-Seq) of LLD participants. Libraries and protocol were developed in the Weizmann Institute of Science. Two different libraries were used, containing microbial and other immunological peptides respectively.
Overview: Our overall long-term goal is to determine risk factors for the complex (multifactorial) disease, venous thromboembolism (VTE), that will allow physicians to stratify individual patient risk and target VTE prophylaxis to those who would benefit most. In this genome-wide association case-control study (1300 cases and 1300 controls) we hope to identify susceptibility variants for VTE. Mutations within genes encoding for important components of the anticoagulant, procoagulant, fibrinolytic, and innate immunity pathways are risk factors for VTE. We hypothesize that other genes within these four pathways or within other pathways also are VTE disease-susceptibility genes. Therefore, we performed a genome wide association (GWA) screen and analysis using the Illumina 660W platform to identify SNPs within 1,300 clinic-based, non-cancer VTE cases primarily from Minnesota and the upper Midwest USA, and 1300 clinic-based, unrelated controls frequency-matched on patient age, gender, myocardial infarction/stroke status and state of residence. This is a subset of a slightly larger candidate gene study using 1500 case-control pairs to identify haplotype-tagging SNPs (ht-SNPs) in a large set of candidate genes (n~750) within the anticoagulant, procoagulant, fibrinolytic, and innate immunity pathways. Study Populations. Cases. VTE cases were consecutive Mayo Clinic outpatients with objectively-diagnosed deep vein thrombosis (DVT) and/or pulmonary embolism (PE) residing in the upper Midwest and referred by Mayo Clinic physician to the Mayo Clinic Special Coagulation Laboratory for clinical diagnostic testing to evaluate for an acquired or inherited thrombophilia, or to the Mayo Clinic Thrombophilia Center. Any person contacted to be a control but discovered to have had a VTE was evaluated for inclusion as a case. Cases were primarily residents from Minnesota, Wisconsin, Iowa, Michigan, Illinois, North or South Dakota, Nebraska, Kansas, Missouri and Indiana. A DVT or PE was categorized as objectively diagnosed when (a) confirmed by venography or pulmonary angiography, or pathology examination of thrombus removed at surgery, or (b) if at least one non-invasive test (compression duplex ultrasonography, lung scan, computed tomography scan, magnetic resonance imaging) was positive. A VTE was defined as: Proximal leg deep vein thrombosis (DVT), which includes the common iliac, internal iliac, external iliac, common femoral, superficial [now termed "femoral"] femoral, deep femoral [sometimes referred to as "profunda" femoral] and/or popliteal veins. (Note: greater and lesser saphenous veins, or other superficial or perforator veins, were not included as proximal or distal leg DVT). Distal leg DVT (or "isolated calf DVT"), which includes the anterior tibial, posterior tibial and/or peroneal veins. (Note: gastrocnemius, soleal and/or sural [e.g., "deep muscular veins" of the calf] vein thrombosis was not included as distal leg DVT). Arm DVT, which includes the axillary, subclavian and/or innominate (brachiocephalic) veins. (Note: jugular [internal or external], cephalic and brachial vein thrombosis was not included in "arm DVT"). Hepatic, portal, splenic, superior or inferior mesenteric, and/or renal vein thrombosis. (Note: ovarian, testicular, peri-prostatic and/or pelvic vein thrombosis was not included). Cerebral vein thrombosis (includes cerebral or dural sinus or vein, saggital sinus or vein, and/or transverse sinus or vein thrombosis). Inferior vena cava (IVC) thrombosis Superior vena cava (SVC) thrombosis Pulmonary embolism Patients with VTE related to active cancer, antiphospholipid syndrome, inflammatory bowel disease, vasculitis, a rheumatoid or other autoimmune disorder, a vascular anomaly (e.g., Klippel-Trénaunay syndrome, etc.), heparin-induced thrombocytopenia, or a mechanical cause for DVT (e.g., arm DVT or SVC thrombosis related to a central venous catheter or transvenous pacemaker, portal and/or splenic vein thrombosis related to liver cirrhosis, IVC thrombosis related to retroperitoneal fibrosis, etc.), with hemodialysis arteriovenous fistula thrombosis, or with prior liver or bone marrow transplantation were excluded. Controls. A Mayo Clinic outpatient control group was prospectively recruited for this study. Controls were frequency-matched on the age group (18-29, 30-39, 40-49, 50-59, 60-69, 70-79, and 80+ years), sex, myocardial infarction/stroke status, and state of residence distribution of the cases. We selected clinic-based controls using a controls' database of persons undergoing general medical examinations in the Mayo Clinic Departments of General Internal Medicine or Primary Care Internal Medicine. Additionally persons undergoing evaluation at the Mayo Clinic Sports Medicine Center, and the Department of Family Medicine were screened for inclusion as controls. This study is part of the Gene Environment Association Studies initiative (GENEVA, http://www.genevastudy.org) funded by the trans-NIH Genes, Environment, and Health Initiative (GEI). The overarching goal is to identify novel genetic factors that contribute to venous thrombosis through large-scale genome-wide association studies of 1,300 clinic-based, VTE cases and 1300 clinic-based, unrelated controls. Genotyping was performed at the Johns Hopkins University Center for Inherited Disease Research (CIDR). Data cleaning and harmonization were done at the GEI-funded GENEVA Coordinating Center at the University of Washington.
Aims and objectives 1. To produce a ‘first generation map’ of mutational burdens and mutational processes that operate in normal human tissues. 2. To examine clonal units and their distribution across normal human tissues with the emphasis on these particular areas: a) Tissues with an architecturally defined unit: Are architectural structures populated by a progeny derived from a single stem cell? Are clonal units confined to a given architectural structure? Examples of tissues where such approach will be used include prostate gland (acini and ducts), small bowel (crypts), thyroid gland (follicles) and others. b) Tissues without an architecturally defined unit: What is the average size of clonal populations? This group includes stratified/pseudostratified epithelia with a basal layer within which there are stem cells that give rise to a progeny of cells showing upwards migration and lateral expansion (e.g. urothelium, cervical squamous epithelium, respiratory epithelium). This approach can also be used in tissues with a sheet-like cell arrangement, for example brain and adrenal gland. Methods To answer these questions, we will use a range of normal human tissue samples which have already been collected from a single deceased individual. The samples are currently stored in a -80C freezer. Ethanol fixed frozen sections will be prepared from these biopsies. Putative clonal units will be identified and dissected out using laser capture microscopy. DNA extraction will be performed using the in-house (CGP) protease based method. In terms of sequencing methods, the project will be split into 2 phases (2 different approaches): - Phase 1: This part of the project will utilise a combination of low input library preparation (developed by Peter Ellis) and standard whole genome sequencing (HiSeqX). The phase has already started (December 2016). This approach will be particularly useful in investigation of mitotically active tissues. - Phase 2: This part of the project will utilise a combination of low input library method (Peter Ellis) and Bottle-neck sequencing (BotSeqS). BotSeqS is a type of duplex sequencing method that offers a more accurate variant calling and allows genome interrogation at a single cell level. This method is currently being developed and is expected to be implemented in 3-6 months (March-April 2017). This approach will be particularly useful for post-mitotic tissues and tissues without pre-defined architectural units.
