Search Results - EGA European Genome-Phenome Archive

Determination_of_cell_specific_regulatory_enhancers_in_hematopoetic_models

The BLUEPRINT project is a large-scale project investigating epigenetic mechanisms involved in blood formation, in health and disease. The human variation workpackage (WP10) of the project seeks to characterize the effect of common sequence variation on the epigenome status of a cell. To do this, the project will use highly purified blood cells to minimise “experimental noise” and therefore enhance the power to discover modest effects. Two peripheral blood cell types, the CD14+CD16- monocyte (an important central orchestrator of adaptive immunity and a bridge between innate and adaptive immunity) and the CD65+CD9- neutrophilic granulocyte (the frontline cell for innate immunity) have been selected for this purpose. The two types of cells will be obtained at high purity from adult blood (AB) of 200 healthy males and females, respectively. Cells will be purified by using already validated and fully operational protocols that are based on density gradient centrifugation of the buffy coat obtained from whole blood, followed by magnetic bead-based purification using monoclonal antibodies against Cluster of Differentiation (CD) lineage-specific cell surface markers. This data set contains functional genomics data for gene expression and chromatin state.

Study EGAS00001000586

Integrative_genome_profiling_in_AML

AML emerges as a consequence of accumulating independent genetic aberrations that direct regulation and/or dysfunction of genes resulting in aberrant activation of signalling pathways, resistance to apoptosis and uncontrolled proliferation. Given the significant heterogeneity of AML genomes, AML patients demonstrate a highly variable response rate and poor median survival in response to current chemotherapy regimens. For the past 4 years we have conducted gene expression profiling on purified bone marrow populations equating to normal haematopoietic stem and progenitor cells from healthy subjects and patients with de novo AML in order to identify AML signatures of aberrantly expressed genes in cancer versus normal. We are now applying a series of bioinformatic methodologies combined with clinical and conventional diagnostic data to establish novel genomics strategies for improved prognostication of AML. Additionally, we use our AML signatures to unravel oncogenic signalling pathway activities in AML patients and test inhibitory drugs for these pathways inn preclinical therapeutic programmes. We consider that superimposing GEP and clinical data for our AML patient cohort with additional data on their mutational status will significantly improve the prognostic power of the study as well as unravel yet unknown mutations associated with aberrant signalling activities of oncogenic pathways.

Study EGAS00001000858

Epigenome wide DNA methylation assay of gingivo-buccal oral squamous cell carcinoma using single base resolution high throughput array

Gingivo-buccal oral squamous cell carcinoma (OSCC-GB) is the most common cancer among men in India and is associated with high mortality. Although OSCC-GB is known to be quite different from tongue cancer in its genomic presentation and its clinical behavior, it is treated identically as tongue cancer. Predictive markers of prognosis and therapy that are specific to OSCC-GB are, therefore, required. To achieve this, we have carried out epigenomic (n=87) profiling of paired tumor-normal tissues collected from OSCC-GB patients from India and genome-wide DNA methylation assays were performed. DNA was isolated using DNeasy Blood and Tissue Kit (Qiagen). The purity and concentration was estimated using NanoDrop 2000 (Thermo Fisher Scientific). Approximately 500 ng genomic DNA from each sample was used for sodium bisulfite conversion using the EZ DNA methylation Gold Kit (Zymo Research, USA). Genome-wide DNA methylation was assayed using iScan (Illumina), for paired tumour and adjacent normal samples of 25 patients using the Infinium Human Methylation450 BeadChip and of 62 patients using the Infinium MethylationEPIC BeadChip.

Study EGAS00001003896

The Egyptian Collaborative Cardiac Genomics (ECCO-GEN) Project: Defining a Healthy Volunteer Cohort

The integration of comprehensive genomic and phenotypic data from diverse ethnic populations offers unprecedented opportunities towards advancements in precision medicine and novel diagnostic technologies. Current reference genomic databases are not representative of the global human population, making variant interpretation challenging, especially in underrepresented populations such as the North African population. To address this, the Egyptian Collaborative Cardiac Genomics (ECCO-GEN) Project launched a study comprising 1000 individuals free of cardiovascular disease (CVD). Here, we present the first 391 Egyptian healthy volunteers (EHVols) recruited to establish a pilot phenotyped control cohort. All individuals underwent detailed clinical investigation, including cardiac MRI, and were sequenced using a targeted panel of 174 genes with reported roles in inherited cardiac conditions (ICC). We identified 1,262 variants in 27 cardiomyopathy genes of which 15.1% were not captured in current global and regional genetic reference databases (here: gnomAD and Great Middle Eastern (GME) Variome). The ECCO-GEN project aims at defining the genetic landscape of an understudied population and providing individual-level genetic and phenotypic data to support future studies in CVD and population genetics.

Study EGAS00001004434

Duplexseq_of_the_interstrand_crosslinks_WGS

One of the most dangerous forms of DNA damage are interstrand crosslinks (ICLs), which covalently crosslink the two strands of the DNA double helix. The repair of these lesions is crucial for cellular survival due to their ability to block transcription and DNA replication. Initially, the major pathway that has been described in ICL repair involves a network of 22 genes that are mutated in a severe human genetic disease known as Fanconi Anemia (FA). Using synthetic lethality screens in the near-haploid human HAP1 cell line, we recently identified two potentially novel regulators of ICL repair, C1orf112 and THAP12. Loss of C1orf112 and THAP12 causes hypersensitivity to ICL-inducing DNA damaging agents, such as Mitomycin C (MMC). Additionally, C1orf112-depleted cells show elevated levels of micronuclei and accumulation of DNA damage in S-phase. To better understand how C1orf112 and THAP12 mediate the repair of ICLs, we want to perform mutational signature analysis, using the BotSeq method. Therefore, WT, C1orf112 and THAP12 knockout cells were cultured in vehicle or MMC treated conditions for 10 days and the genomic DNA was isolated. FANCA and FANCD2 knockout cells are taken along as controls in this experimental setting.

Study EGAS00001006545

H3Africa - Deciphering Developmental Disorders in Africa

Developmental disorders are typically rare conditions, causing an impairment in physical, learning, language, or behavioural areas. Genetic heterogeneity and highly variable clinical manifestations make diagnosing developmental disorders particularly challenging. Developmental disorders are increasing in prevalence in low- and middle-income countries, partly due to effective prevention and treatment of infectious diseases leading to a decrease in childhood mortality. New sequencing technologies are used effectively in the diagnosis of rare diseases and results can impact clinical practice significantly. Despite this international trend, very little implementation of these new approaches has taken place in low-resource settings, especially in Africa. The Deciphering Developmental Disorders in Africa (DDD-Africa) study aims to take advantage of an unbiased genotype-driven approach to improve healthcare services for patients. The study aims to recruit and perform detailed clinical phenotyping and exome sequencing (ES) on 500 African patients with a developmental disorder in whom a genetic diagnosis has not been confirmed. Where available, parents are also included in sequencing efforts. The project has two active research sites in Johannesburg (South Africa) and Kinshasa (Democratic Republic of Congo) representing diversity in geography, clinical, socio-economic, genetic and environmental factors.

Study EGAS00001008319

A Single-cell Atlas of Progressive TKI Resistance in Chronic Myeloid Leukemia

High-dimensional scRNA seq and CyTOF were used to identify features predictive of treatment outcome at diagnosis. An optimal TKI response was characterised by erythroid lineage skewing of the CD34+ HSPC compartment. While TKI-resistant CP was reminiscent of a BC-like state, where HSPCs were enriched for inflammation, stemness and quiescence. We designed a machine-learning approach which assessed the prognostic potential of all 32 sub-populations of our scRNA seq dataset. LSCs and NK populations harboured the highest prognostic power at diagnosis. Within the LSCs, erythroid lineage priming and MYC activation were features of an optimal and poor TKI responses, respectively. With the NK cell compartment, apart from a higher abundance of NK cells in TKI optimal responders, a memory-like HLA-DR+ adaptive NK and KLRC1+ NK populations were hallmarks of an optimal and poor TKI responses, respectively. Mechanistically, both cell intrinsic and extrinsic mechanisms contributed towards the higher sensitivity of EPs to TKI therapy. In summary, our high-dimensional single-cell atlas of TKI resistance highlights pivotal transcriptional features associated with TKI-resistance disease, some of which have the potential to be exploited as biomarkers.

Study EGAS00001005509

Genome Diversity in Africa Project: Benin (2021-02-16)

Globally, human populations show structured genetic diversity as a result of geographical dispersion, selection and drift. Understanding this genetic variation can provide insights into the evolutionary processes that shape both human adaptation and variation in disease. Populations from SSA have the highest levels of genetic diversity. This characteristic, in addition to historical genetic admixture, can lead to complexities in the design of studies assessing the genetic determinants of disease and human variation. However, such studies of African populations are also likely to provide new opportunities to discover novel disease susceptibility loci and variants and refine gene-disease association signals. A systematic assessment of genetic diversity within SSA would facilitate genomic epidemiological studies in the region. The Genome Diversity in Africa Project (GDAP) aims to produce a comprehensive catalogue of human genetic variation in SSA, including single nucleotide polymorphisms (SNPs), structural variants, and haplotypes. This resource will make a substantial contribution to understanding patterns of genetic diversity within and among populations in SSA, as well as providing a global resource to help design, implement and interpret genomic studies in SSA populations and studies comprising globally diverse populations, complementing existing genomic resources. Specifically, we plan to carry out high depth whole genome sequencing of up to 2000 individuals across Africa (25 individuals from each ethnolinguistic group). Our scientific objectives are to: 1) develop a resource that provides a comprehensive catalogue of genetic variation in populations from SSA accessible to the global scientific community; 2) characterise population genetic diversity, structure, gene flow and admixture across SSA; 3) develop a cost-efficient, next-generation genotype array for diverse populations across SSA; and 4) facilitate whole genome-sequencing association studies of complex traits and diseases by developing a reference panel for imputation and resource for enhancing fine-mapping disease susceptibility loci. These scientific objectives will be supported by cross-cutting operational activities, including network and management of the consortium, research ethics, and research capacity building in statistical genetics and bioinformatics This data is part of a pre-publication release. For information on the proper use of pre-publication data shared by the Wellcome Trust Sanger Institute (including details of any publication moratoria), please see http://www.sanger.ac.uk/datasharing/ . This dataset contains all the data available for this study on 2021-02-16.

Dataset EGAD00001006970

Studying the cellular diversity of the human hypothalamus

We use single-cell and spatial transcriptomics to catalogue cellular populations and their locations in the human hypothalamus

Study EGAS50000000716

johannesburg_20150706_autosomes

Genotype data and (in binary PLINK format) and imputed data (with merged 1000Gp3 and AGVP reference panel in GEMMA BIMBAM dosage format) for 750 individuals from Respiratory and Meningeal Pathogens Unit in Soweto, South Africa - autosomes.

Dataset EGAD00010002582

Genome sequencing of HCC from a Chinese cohort

project aims to understand somatic variants, differential expressed genes and signaling pathways in HBV- and NASH related HCC tumors.

Study EGAS00001001783

Dataset-linking-WGS-and-WES-files-from-EGAS00001004276-via-README-for-new-study-EGAS00001005327

This dataset contains 538 Tumor and Control WGS and WES files for samples already submitted and published in study EGAS00001004276

Dataset EGAD00001007817

Pharmacogenomic Evaluation of Antihypertensive Responses (PEAR and PEAR-2)

The primary aim of the Pharmacogenomic Evaluation of Antihypertensive Responses grant (funded by NIH Pharmacogenomic Research Network grant U01 GM074492) was to identify genetic determinants of blood pressure response and adverse events after antihypertensive treatments. Two different clinical trials with genomic information available were included: PEAR-1 and PEAR-2 studies. The PEAR-1 study (clinicaltrials.gov identifier NCT00246519) was a randomized controlled clinical trial evaluating genetic determinants of BP responses and adverse metabolic responses to atenolol and hydrochlorothiazide (HCTZ) monotherapy and in combination (PMID: 19249413). Briefly, PEAR-1 recruited 768 hypertension individuals with uncomplicated hypertension who were randomized to either monotherapy of atenolol 50 mg daily or HCTZ 12.5 mg daily for 3 weeks, followed by dose titration to 100 mg and 25 mg daily, then the combination therapy. BP and metabolic responses to monotherapy and combination therapy were assessed after an average of 9 weeks of antihypertensive treatment. BP was measured using three different methods: home, office and ambulatory. For the BP analysis, a composite weighted average of the office, home, ambulatory daytime and nighttime BP responses was calculated based on the row sums of the inverse of the inter-method covariance matrices. Genomic DNA from PEAR-1 participants was genotyped using the Illumina Human Omni1MQuad BeadChip (Illumina, San Diego, CA, USA). The PEAR-2 study was a multicenter sequential monotherapy clinical trial (clinicaltrials.gov identifier NCT01203852) evaluating genetic determinants of BP response to metoprolol monotherapy and chlorthalidone monotherapy. After a washout period (if necessary), eligible hypertensive patients with uncomplicated hypertension received metoprolol tartrate 50 mg twice daily for 3 weeks and the dose was increased to 100 mg twice daily for an additional six weeks if an inadequate response was observed (>120/70 mm Hg and heart rate >55 beats/min). After second washout period, patients received chlorthalidone monotherapy. Home and office BP measurements were collected in PEAR-2 study. We have previously demonstrated that home BP is the more informative single BP measurement compared to the office BP measurement. Therefore, home BP is the phenotype used for the genome-wide association analysis for PEAR-2. PEAR-2 samples were genotyped using the Illumina Human Omni2.5S Beadchip (Illumina, San Diego, CA, USA).

Study phs000649

Phase II Study of Cryoablation and Post-Progression Immune Checkpoint Inhibition in Metastatic Melanoma

Percutaneous cryoablation guided by imaging is a well-established, minimally invasive treatment for oncological conditions. We posited that cryoablation could alter the immune microenvironment by directly influencing the tumor, potentially eliciting an anti-tumor response in cases resistant to immune checkpoint inhibition (ICI). In this non-randomized phase II single-center study (NCT03290677), individuals with unresectable melanoma experiencing progression on ICI underwent cryoablation in a single progressing metastasis, while ICI was continued for at least two additional cycles. The main objectives were to assess safety and feasibility and to evaluate tumor response in non-ablated lesions. Between May 2018 and July 2020, 17 patients participated in the study. The treatment regimen proved safe, revealing an objective response rate of 23.5% and a disease control rate of 41% (comprising 4 partial responses and 3 stable diseases). In our investigation into the factors influencing response to cryoablation therapy in ICI-resistant melanoma, we conducted single-cell RNA sequencing (scRNA-seq) using both 10x Genomics and Smart-seq2 technologies on biopsies from metastatic sites of 15 patients. We collected pre-treatment samples from all patients and post-treatment samples from 5 patients, totaling 20 samples. After quality control, excluding cells specific to anatomical sites or rare cell types (e.g., alveolar type II, neurons), and batch correction, we analyzed 49,071 single cells spanning melanocyte, endothelial, stromal, T, myeloid, and B/plasma cell lineages. Differential gene expression (DGE) analysis between myeloid cells identified the genes MARCKS and IL10, two genes involved in anti-inflammatory responses that can inhibit macrophages activation to be associated with failed response. Moreover, DGE analysis of T cells identified the gene TXK, which acts as a Th1 transcription factor, and the gene CMKLR1 (chemerin-like-receptor-1), which triggers migration of CD8 T-cells to be upregulated in patients who benefited from cryoablation treatment. In contrast, MTHFD2 and GGH, two genes involved in one-carbon metabolism and the folate cycle, were upregulated in T cells from patients who did not respond to therapy. Our analysis revealed a significant increase in B/plasma cells in patients who responded positively to the therapy combination, along with an enrichment of oxidative phosphorylation in T cells among non-responsive patients with progressive disease. These findings advocate for further investigation into this innovative and synergistic therapeutic approach.

Study phs003579

Clinical Proteomic Tumor Analysis Consortium (CPTAC) Proteogenomic Confirmatory Study of Breast, Colon, Lung, and Ovarian Tumors

Recently, significant progress has been made in characterizing and sequencing the genomic alterations in statistically robust numbers of samples from several types of cancer. For example, The Cancer Genome Atlas (TCGA), International Cancer Genome Consortium (ICGC) and other similar efforts are identifying genomic alterations associated with specific cancers (e.g., copy number aberrations, rearrangements, point mutations, epigenomic changes, etc.). The availability of these multi-dimensional data to the scientific community sets the stage for the development of new molecularly targeted cancer interventions. Understanding the comprehensive functional changes in cancer proteomes arising from genomic alterations and other factors is the next logical step in the development of high-value candidate protein biomarkers. Hence, proteomics can greatly advance the understanding of molecular mechanisms of disease pathology via the analysis of changes in protein expression, their modifications and variations, as well as protein-protein interaction, signaling pathways and networks responsible for cellular functions such as apoptosis and oncogenesis. Realizing this great potential, the NCI launched the second phase of the CPTC initiative in September 2011. Renamed the Clinical Proteomic Tumor Analysis Consortium, CPTAC is beginning to leverage its analytical outputs from Phase I to define cancer proteomes on genomically-characterized biospecimens. The purpose of this integrative approach is to provide the broad scientific community with knowledge that links genotype to proteotype and ultimately phenotype. The data contained in this dataset are derived from samples designed to confirm CPTAC findings from the TCGA samples. These confirmatory samples contain breast, ovarian, colon, and lung tumors collected via a protocol optimized for proteomics. Specifically, ischemic time of the sample was controlled and restricted to less than 30 minutes. ACGT, Inc. produced whole exome, mRNAseq, and miRNAseq for these samples. Corresponding proteomic data are available at: https://cptac-data-portal.georgetown.edu/cptacPublic/ The study design was to profile colon, breast, ovarian, and lung tumors both genomically and proteomically. Germline DNA was obtained from blood. Normal control samples for proteomics varied by organ site: adjacent colon tissue for colon cases, contralateral breast tissue for some breast cases, and Fallopian tube fimbria for some ovarian cases. Lung cases had no normal control for proteomic analysis. All cancer samples were derived from primary and untreated tumors.

Study phs000892

Robust detection of translocations in lymphoma FFPE samples using Targeted Locus Capture-based sequencing

Chromosomal translocations with immunoglobin (IG) loci are the classic drivers in a large subset of B-cell lymphomas. Detection of these translocations is important for confirmation of diagnosis and for prognosis and therapy decisions. Currently, molecular diagnosis of translocations in lymphomas is not addressed well by Next Generation Sequencing (NGS). The standard method for detection of translocations is Fluorescence In Situ Hybridization (FISH), which is labor-intensive, and can be difficult to interpret. There is a need for a robust technology that can be standardized. Targeted Locus Capture (TLC) selectively enriches and sequences entire genes based on the crosslinking of physically proximal sequences, and thereby enables complete sequencing of genes of interest, including detection of large structural variants. Because the technology is based on the crosslinking and fragmenting of DNA, it has particular advantages in the analysis of Formalin-Fixed, Paraffin-Embedded (FFPE) samples, in which DNA is inherently crosslinked and fragmented. In order to validate the FFPE-TLC technology as a novel approach for translocation detection in lymphoma samples, we have developed a panel assay containing genes with frequent translocations (MYC, BCL2, BCL6, IG loci). With this assay we have analyzed >140 lymphoma and control FFPE samples of variable input amounts and qualities that had previously been analyzed with FISH, and a subset also with standard targeted NGS. Good concordance with FISH results was observed for both translocation positive and negative samples. In 10 cases for which FFPE-TLC detected a relevant fusion and FISH had been called negative, discordance could be explained by higher sensitivity of FFPE-TLC or by inconclusive FISH results. In a specific case, FFPE-TLC detected a small-distance rearrangement on chromosome 3 that caused a BCL6 fusion but led to insufficient and therefore undetectable break-apart with FISH. Secondly, the FFPE-TLC approach was tested on a set of 19 B-cell lymphoma FFPE samples that had previously been analyzed using standard targeted NGS and FISH and was enriched for discordant results between these methods. FFPE-TLC-based NGS enables more robust translocation calling as the detection relies on broad sequencing coverage across the translocation partner rather than on breakpoint sequences only. In 3 cases, FFPE-TLC could proof false negative calls in standard targeted NGS due to breakpoints located in regions difficult to capture or to sequence. In 1 case, standard targeted NGS had made a false positive call on a breakpoint sequence that was shown to be caused by a small insertion rather than a genuine translocation. This study shows that FFPE-TLC promises to be a robust alternative for FISH analysis and standard targeted NGS procedures in lymphoma diagnostics and possibly in other cancers with frequent structural variants. The FFPE-TLC approach enables a single, DNA-based NGS test detecting both small mutations and translocations.

Study EGAS00001004760

Expressed Pseudogenes in the Transcriptional Landscape of Human Cancers

In this study, we describe a systematic analysis of pseudogene 'transcription' from an RNA-Seq resource of 293 samples, from 13 cancer and normal tissue types. We observed a highly prevalent, genome-wide expression of pseudogenes that could be categorized as universally expressed or lineage- and/or cancer-specific. We also explored disease subtype specificity and functions of selected expressed pseudogenes. We provide evidence that transcribed pseudogenes are a significant contributor to the transcriptional landscape of cells and are positioned to play significant roles in cellular differentiation and cancer progression. Our work provides a transcriptome resource that enables high-throughput analyses of pseudogene expression.

Study phs000525

Genetic Basis of Cryptorchidism

Non-syndromic cryptorchidism is a common malformation, but the genetic loci that increase susceptibility to cryptorchidism remain unknown. A genome-wide association study (GWAS) was completed to determine whether common allelic variants are associated with susceptibility to cryptorchidism. Two sets of discovery groups were genotyped. Group 1 (559 cases and 1772 controls) was genotyped with HumanHap550v1.0, HumanHap550v3.0 or Human610-quad v1.0. Group 2 (353 cases and 1149 controls) was genotyped with HumanOmniExpress-12v1 or HumanOmniExpress-12v1-1. The sample and marker QCs were performed separately using PLINK (v1.07; http://pngu.mgh.harvard.edu/purcell/plink/) and logistic regression analyses were performed with first and second multidimensional scaling (MDS) components as covariates.

Study phs000986

Estonian Biobank | Estonian Genome Center, University of Tartu

The Estonian Biobank is the population-based biobank of the Estonian Genome Centre of University of Tartu. The biobank is conducted according to the Estonian Gene Research Act and all participants have signed broad informed consent. The cohort size is currently 51,535 people from 18 years of age and up. Metabolite concentrations (over 110; NMR and MS) are available for about 12,000 subjects; metabolic follow-up has been done for more than 2000 donors. GWAS has been performed on 20,000 subjects with different Illumina arrays and 2,500 have whole exomes and 2,400 full sequence. The data for the 2,400 fully sequenced samples is available through dbGaP.

Study phs001230

Small RNA Sequencing across Diverse Biofluids Identifies Optimal Methods for exRNA Isolation

We tested the efficiency and reproducibility of 10 RNA isolation methods on 5 different biofluids. Pooled human plasma and serum, bile and urine were used along with cell culture supernatants from human embryonic stem cells (hESC), primary neonatal rat ventricular myocytes (NRVM) and human cholangiocarcinoma cells (KMBC). 4 RNA isolation methods designed to isolate total RNA from bio fluids without enrichment of exRNA carriers were used. 6 methods that preferentially enriched for exRNA carriers were also compared. Small RNA libraries were constructed using the NEBNext small-RNA library prep. The efficiency and reproducibility of the different RNA isolation methods was compared using small-RNA seq.

Study phs002143

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

Integrative Analysis of Lung Adenocarcinoma in EAGLE (Version 2)

We performed a comprehensive analysis of intratumor heterogeneity of somatic mutations in cancer driver genes, copy number aberrations and DNA methylation in 292 tumor samples from 84 lung adenocarcinoma (LUAD) patients from the Environment And Genetics in Lung cancer Etiology (EAGLE) study. SNVs of 37 established lung cancer driver genes were profiled by deep target sequencing in 180 tumor samples and 55 blood samples and 1 buccal sample from 56 subjects. Somatic copy number alterations were profiled using SNP arrays in 268 tumor samples from 80 subjects. DNA methylation levels were profiled with methylation arrays in 205 tumor samples and 74 normal tissue samples from 68 subjects.

Study phs001169

Whole Exome Characterization of Squamous Cell Lung Cancers (Lung SQCC) from Appalachian Kentucky (APPKY)

This is a pilot study of squamous cell lung cancer and matched normal tissue pairs collected (convenience sample) from patients from Central Appalachia, in Southeastern Kentucky. This study performed whole exome sequencing on tumor and matched normal DNA samples from 51 lung squamous cell carcinoma (SQCC) subjects from Appalachian Kentucky (AppKY). Somatic genomic alteration profiles were compared between the AppKY and TCGA SQCC cohorts. We found that IDH1 and PCMTD1 had higher mutation rates in AppKY versus TCGA. These findings suggest population differences in the genetics of lung SQCC between AppKY and US populations that have implications for personalized treatment for this disease.

Study phs001651

Myocardial Infarction Genetics Exome Sequencing Consortium: Pakistan Risk Of Myocardial Infarction Study

The Pakistan Risk of Myocardial Infarction (PROMIS) study is a retrospective multicenter case-control cohort study of individuals with and without coronary heart disease from Pakistan. Multiple biological samples have been collected from the participants including DNA, plasma, serum, and whole blood. The goal of the study is to recruit 20,000 cases and 20,000 controls of Pakistani descent. All exome sequencing was performed at the Broad Institute of Harvard and MIT; samples sequence capture was performed using either Agilent's SureSelect Human All Exon Kit v2 or Illumina's ICE capture reagent; and sequencing was performed on an Illumina HiSeq 2000 or 2500.

Study phs000917

DNA Methylation age and mortality in the Lothian Birth Cohorts of 1921 and 1936

The study examined the association between DNA methylation age and mortality. Methylation age was estimated in 4 cohorts (including the Lothian Birth Cohorts of 1921 and 1936) and related to subsequent time-to-death. Across all four cohorts there was a strong correlation between predicted methylation age and chronological age. For individuals with a 5 year age acceleration (DNA methylation age - chronological age = 5), there was a meta analysed hazard ratio of mortality of 1.21 [1.14, 1.29]. Phenotype data associated with the study are available through dbGaP, the methylation raw data are available through the European Genome-phenome Archive (EGA; accession number EGAS00001000910).

Study phs000821

16792 results for "sec+and+unspecified+malignant+neoplasm"

in 37.41 milliseconds.