3968 results for "*geneti*"

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• BLUEPRINT ChIP-seq data for cells in the haematopoietic lineages, from adult and cord blood samples.

  ChIP-seq data for cells in the haematopoietic lineages, from adult and cord blood samples.

  Study EGAS00001000326

• Genome_Diversity_in_Africa_Project___GemCode_libraries

  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 Africa 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 Africa would facilitate genomic epidemiological studies in the region.The Genome Diversity in Africa Project (GDAP) will extend and expand the African Genome Variation (AGV) project, an international collaboration aimed to produce a comprehensive catalogue of human genetic variation in Sub-Saharan Africa (SSA). Using a sequencing-based approach, GDA project aims to capture human genetic variation in Africa, 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 Africa, as well as providing a global resource to help design, implement and interpret genomic studies in African populations and studies comprising globally diverse populations, complementing existing genomic resources. Specifically, we plan to carry out whole genome sequencing at high depth (30x) of up to 1000 individuals across Africa (25 individuals from each ethnolinguistic group). We have already completed sequencing from 5 ethno-linguistic groups and we are now adding others.Our scientific objectives are to: 1) develop a resource that provides a comprehensive catalogue of genetic variation in populations from Africa accessible to the global scientific community; 2) characterise population genetic diversity, structure, gene flow and admixture across Africa; 3) develop a cost-efficient, next-generation genotype array for diverse populations across Africa; 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.

  Study EGAS00001001589

• Illumina HumanCoreExome genotyping data from the British Society for Surgery of the Hand Genetics of Dupuytren’s Disease consortium (BSSH-GODD consortium) collection

  Dupuytren's Disease (DD - OMIM126900) is the most common heritable disorder of connective tissue. It is a fibroproliferative disorder of the palmer fascia, causing flexion contractures of affected digits. DD affects men more commonly than women. DD is an archetypal complex disease, with multiple genetic and environmental factors affecting the final expression of the disease phenotype. The incidence increases with age, and the prevalence of DD is therefore increasing as the UK population ages. Half of all patients present before age 60. DD causes significant functional impairment, and severe contractures can lead to permanent disability. The mainstay of current treatment is surgery, but recurrence and complications are both high. For severe contractures, the only suitable treatment option is amputation. The direct costs to the NHS are high, and underestimate the true economic costs to society. We collected salivary samples from adults in the UK who have had surgery for DD. We have genotyped these samples using the Illumina HumanCoreExome Beadchips. https://research.ndorms.ox.ac.uk/public/dupuytrens/what-is-dupuytrens-disease/

  Study EGAS00001001206

• Breast_Cancer_Matched_Pair_Cell_Line_Whole_Genomes

  We propose to definitively characterise the somatic genetics of matched pair breast cancer cell lines through generation of comprehensive catalogues of somatic mutations by high coverage genome sequencing coupled with integrated transcriptomic and methylation analyses.

  Study EGAS00001000166

• Adenoma to Carcinoma transition in Colorectal Cancer

  Although colorectal carcinoma development is well accepted as a step-wise and sequential process, it is commonly investigated using non-sequential adenoma and carcinoma samples. Here we compared molecular pathologies of the earliest carcinoma stages with those in their adenomatous precursors to unravel common and divergent genetic traits between matched neoplasms with a shared evolutionary history but different contemporary biology.

  Study EGAS00001003468

• Combination_therapies_for_personalized_cancer_medicine

  It is the ambition of the team formed by members of the Netherlands Cancer Institute (NKI) and the Cancer Genome Project at the Wellcome Trust Sanger Institute (WTSI) to unravel the genomic and phenotypic complexity of human cancers in order to identify optimal drug combinations for personalized cancer therapy. Our integrated approach will entail (i) deep sequencing of human tumours and cognate mouse tumours; (ii) drug screens in a 1000+ fully characterized tumour cell line panel; (iii) high-throughput in vitro and in vivo shRNA and cDNA drug resistance and enhancement screens; (iv) computational analysis of the acquired data, leading to significant response predictions; (v) rigorous validation of these predictions in genetically engineered mouse models and patient-derived xenografts. This integrated effort is expected to yield a number of combination therapies and companion-diagnostics biomarkers that will be further explored in our existing clinical trial networks.

  Study EGAS00001000655

• BASIS_RNAseq

  We propose to definitively characterise the somatic genetics of ER+ve, HER2-ve breast cancer through generation of comprehensive catalogues of somatic mutations in 500 cases by high coverage genome sequencing coupled with integrated transcriptomic and methylation analyses.

  Study EGAS00001000707

• Exome sequencing of uterine leiomyosarcomas

  Uterine leiomyosarcomas (ULMSs) are aggressive smooth muscle tumors associated with poor clinical outcome. Despite previous cytogenetic and molecular studies, their molecular background has remained elusive. To examine somatic variation in ULMS, we performed exome sequencing on 19 tumors. Altogether 43 genes were mutated in at least two ULMSs. Most frequently mutated genes included tumor protein P53 (TP53; 6/19; 33%), alpha thalassemia/mental retardation syndrome X-linked (ATRX; 5/19; 26%), and mediator complex subunit 12 (MED12; 4/19; 21%). Unlike ATRX mutations, both TP53 and MED12 alterations have repeatedly been associated with ULMSs. All the observed ATRX alterations were either nonsense or frameshift mutations. ATRX protein levels were reliably analyzed by immunohistochemistry in altogether 44 ULMSs, and the majority of tumors (23/44; 52%) showed clearly reduced expression. Loss of ATRX expression has been associated with alternative lengthening of telomeres (ALT), and thus the telomere length was analyzed with telomere-specific fluorescence in situ hybridization. The ALT phenotype was confirmed in all ULMSs showing diminished ATRX expression. Exome data also revealed one nonsense mutation in death-domain associated protein (DAXX), another gene previously associated with ALT, and the tumor showed ALT positivity. Aberrant expression of both TP53 and ATRX were associated with poor overall survival. In conclusion, exome sequencing revealed that TP53, ATRX, and MED12 are frequently mutated in ULMSs. ALT phenotype was commonly seen in tumors, indicating that ATR inhibitors, which were recently suggested as possible new drugs for ATRX-deficient tumors, could provide a potential novel therapeutic option for ULMS.

  Study EGAS00001001612

• PAGE: Prenatal Assessment of Genomes and Exomes

  The Prenatal Assessment of Genomes and Exomes (PAGE) study is a multicentre prospective trial, performing exome sequence analysis on samples from 1000 families with structural anomalies in prenatal ultrasound screening but normal aneuploidy results. The data will enable discovery of novel genetic disorders and increase the diagnostic yield. Where appropriate, results will be reported back to the families at the end of the pregnancy, after thorough clinical review. Ultimately, the translation of the acquired know-how into cost-effective prenatal diagnostic sequencing will improve genetics-derived prognoses and allow more informed parental counselling as well as management of pregnancy and childbirth.

  Study EGAS00001001713

• Fixation effects on variant-calling in a clinical resequencing panel

  Formalin fixation is the standard method for preservation of tissue for diagnostic purposes, including pathological review and molecular assays. However, this method is known to cause artifacts that can affect the accuracy of molecular genetic tests. We assessed the applicability of alternative fixatives to determine whether these perform significantly better on next-generation sequencing assays, and whether adequate morphology is retained for primary diagnosis, in a prospective study using a clinical-grade laboratory-developed targeted resequencing assay. We examined and quantified several parameters relating to sequencing quality and variant-calling from tumor and normal colon epithelial tissues. We identify one alterative fixative, Sakura Universal Molecular Fixative that suppresses many formalin-related artifacts while retaining adequate morphology for pathological review.

  Study EGAS00001003507

• Whole-Genome sequencing of hepatocellular carcinomas

  The French ICGC project on liver tumors is coordinated by Pr Jessica Zucman-Rossi and funded by Inca (French Institute for Cancer). The aim of the present project is to identify the catalog of somatic and germline mutations in liver tumors using whole genome and whole exome sequencing together with CGH-SNP, methylome and transcriptomic profiling. For this purpose, a series of 500 liver tumors are collected through the French National Liver Collection and these samples will be analyzed using the different omics technologies. The data will be deposited in the ICGC and EGA database to be publically available for the scientific community. Hepatocellular carcinoma (HCC) accounts for more than 90% of liver cancers, and is a major health problem. It is the 3rd cause of cancer-related mortality. Advances in genomic analyses have formed a comprehensive understanding of different underlying pathobiological layers resulting in hepatocarcinogenesis. Thus, the development of next-generation sequencing technologies has made it possible to generate more comprehensive catalogues of somatic alteration events (single nucleotide substitutions, structural variations, and epigenetic changes) in liver cancer genome than ever before. The dataset will include 50 whole genome sequencing tumor/germline pairs, of which 6 are deposited in February 2014.

  Study EGAS00001000706

• Evolutionary origin and methylation status of human intronic CpG islands that are not present in mouse

  Imprinting of the human RB1 gene is due to the presence of a differentially methylated CpG island (CGI) in intron 2, which is part of a retrogene derived from the PPP1R26 gene on chromosome 9. The murine Rb1 gene does not have this retrogene and is not imprinted. We have investigated whether the RB1/Rb1 locus is unique with respect to these differences. For this we have compared the CGIs from human and mouse by in silico analyses and found out that there are at least 2033 human intronic CGIs that are not present in the mouse. Among these CGIs, 104 show sequences similarities elsewhere in the human genome, which suggests that they arose by retrotransposition. We could narrow down the time points when most of these CGIs appeared during evolution. Their methylation status was analysed in two monocyte methylome datasets from whole genome bisulfite sequencing and in 18 published methylomes. Five CGIs appear to be differentially methylated, which suggests that they are subject of genomic imprinting. They are located in introns of the following genes: RB1, ASRGL1, PARP11, PDXDC1 and MYO1D. Four of these CGIs are parts of retrogenes. Our study supports the notion that imprinting builds on host defence mechanisms by which the genome protects itself against retrotransposed and foreign DNA and that the epigenetic fate of the retrotransposed DNA depends on selective forces at the integration site.

  Study EGAS00001000719

• Probabilistic modeling of personalized drug combinations from integrated chemical screen and molecular data in sarcoma

  Background: Cancer patients with advanced disease exhaust available clinical regimens and lack actionable genomic medicine results, leaving a large patient population without effective treatments options when their disease inevitably progresses. To address the unmet clinical need for evidence-based therapy assignment when standard clinical approaches have failed, we have developed a probabilistic computational modeling approach which integrates sequencing data with functional assay data to develop patient-specific combination cancer treatments. Methods: Tissue taken from a murine model of alveolar rhabdomyosarcoma was used to perform single agent drug screening and DNA/RNA sequencing experiments; results integrated via our computational modeling approach identified a synergistic personalized two-drug combination. Cells derived from the tumor were allografted into mouse models and used to validate the personalized two-drug combination. Computational modeling of single agent drug screening and RNA sequencing of multiple heterogenous sites from a single patient’s epithelioid sarcoma identified a personalized two-drug combination effective across all tumor regions. The heterogeneity-consensus combination was validated in a xenograft model derived from the patient’s primary tumor. Cell cultures derived from human and canine undifferentiated pleomorphic sarcoma were assayed by drug screen; computational modeling identified a resistance-abrogating two-drug combination common to both cell cultures. This combination was validated in vitro via a cell regrowth assay. Results Our computational modeling approach addresses three major challenges in personalized cancer therapy: synergistic drug combination predictions (validated in vitro and in vivo in a genetically engineered murine cancer model), identification of unifying therapeutic targets to overcome intra-tumor heterogeneity (validated in vivo in a human cancer xenograft), and mitigation of cancer cell resistance and rewiring mechanisms (validated in vitro in a human and canine cancer model). Conclusions These proof-of-concept studies support the use of an integrative functional approach to personalized combination therapy prediction for the population of high-risk cancer patients lacking viable clinical options and without actionable DNA sequencing-based therapy.

  Study EGAS00001003564

• Pangenomic classification of pituitary adenomas

  Pituitary neuroendocrine tumors (PitNETs) are common. They are classified in five main histological types: PitNETs of POU1F1 (Pit1) lineage -lactotroph, somatotroph and thyrotroph -, gonadotroph, and corticotroph PitNETs. Pituitary tumorigenesis is poorly understood. We report here a pangenomic characterization of 134 PitNETs from all types, based on exome, genome, transcriptome, miRnome and methylome. Pit1 lineage was associated with a specific epigenetic signature of diffuse DNA hypomethylation, and correlated with expression of Pit1 markers and chromosomal instability. 45% of somatotroph PitNETs showed GNAS mutations. GNAS-wild type somatotroph showed a distinct transcriptome profile, expressing gonadotroph transcription factor NR5A1 (SF1). Sparsely granulated somatotroph PitNETs was classified apart from somatotroph, owing to a thyrotroph transcriptome signature. 43% of corticotroph PitNETs showed USP8 mutations, sharing a low epithelial-mesenchimal transition (EMT) transcriptome signature. Silent corticotroph PitNETs showed a gonadotroph transcriptome signature evoking transdifferentiation, and lost somatostatin target SSTR5 expression.

  Study EGAS00001003642

• Whole genome sequencing of six ethnic groups from Burkina Faso, Cameroon, and Tanzania

  We conducted low-coverage (~10x) sequencing of six ethnic groups from three malaria-endemic countries in sub-Saharan Africa, with the aim of characterising genetic diversity and improving imputation performance for genotyped samples in these populations. This data is part of a pre-publication release and is available under managed access. Please see https://www.malariagen.net/data/terms-use/human-gwas-data for more information on MalariaGEN data access policies. The purpose of the project was to support the discovery and understanding of genetic variants that influence human disease. Specifically defined goals were: a. the discovery of single nucleotide variants at frequencies of 1% or higher in diverse populations, b. even more comprehensive discovery (variants down to frequencies of 0.1 - 0.5%) in functional gene regions, and c. discovery of structural variants, such as copy number variants, other insertions and deletions, and inversions, including sequence-level understanding of breakpoints.

  Study EGAS00001003648

• Succession Of Transiently Active Tumour-Initiating Cell Clones inHuman Pancreatic Cancer

  To elucidate whether newly acquired genetic alterations during serial transplantation of patient derived primary pancreatic cancer cultures contribute to the observed clonal dynamics in vivo, all coding genes of two patient derived primary cultures and derived genetically marked serial xenografts (1°/2°/3°) were sequenced.

  Study EGAS00001000882

• Developmental_Dysplasia_of_the_Hip__DDH_

  The National Joint Registry for England and Wales (NJR) has become established as one of the largest repositories of clinical information about patients undergoing hip and knee replacement. The primary aim of this proposal is to examine the feasibility of adding value to that clinical information by partnering it with a DNA dataset to allow its use to be extended to the study of the underlying pathogenesis of diseases of the hip and knee, and the complications of their treatment. We will do this 1) by establishing a mechanism for accessing and linking pseudo-anonymised demographic and phenotype data between the NJR database and the proposed DNA Biobank; 2) by validating the collection of postal DNA samples from consenting NJR patients; and 3) by genotyping genome-wide 900 patients with the condition developmental dysplasia of the hip (DDH) to find variants that play a role in this heritable condition. The successful demonstration that the NJR can be used to establish a DNA Biobank will provide a powerful platform to examine the genetic basis for a wide range of joint diseases, and the complications of their treatment. This proposal is to carry out the genotyping portion of this project on the current CoreExome array

  Study EGAS00001000916

• Clinical and Molecular Investigation of Familial CEBPA-mutated Acute Myeloid Leukaemia

  Myelodysplastic syndromes (MDS) and acute myeloid leukaemia (AML) are clonal diseases arising from the sequential acquisition of genetic aberrations in haematopoietic stem cells. Whilst the aetiology is predominantly sporadic, rare reports describe the autosomal dominant inheritance of MDS and AML (familial MDS/AML), often presenting in younger patients (<40 years of age) with a germline mutation in one of three haematopoietic transcription factors: RUNX1, CEBPA and GATA2. The clinical recognition of familial disease can be challenging due to wide variations in phenotype, latency and transmission, complicated further by the patients’ awareness and reporting of affected relatives. Distinct clinical manifestations have however been reported for each genetic subtype and whilst RUNX1 and GATA2 mutations can harbour prolonged dysplastic or cytopenic phases, germline CEBPA mutations universally present with AML de novo. Our group were the first to describe germline CEBPA mutations in 3 related individuals, all of whom developed AML between 10-30 years of age. The initial pedigree together with those described in the intervening period, were predominantly isolated case reports with limited follow up, hence long term outcomes for this group of patients remain poorly defined. This contrasts with CEBPA mutations occurring in 10-15% of sporadic AML with normal karytoype (NK-AML), where double mutations (CEBPAdm, found in approximately 50% of all CEBPA-AML) are considered a unique molecular entity, associated with favourable clinical outcomes. In sporadic and familial CEBPAdm AML, N’ terminal mutations enforce translation of the shorter P30-kDa isoform and are typically accompanied by C’ terminal insertions or deletions (disrupting the DNA-binding and/or Leucine zipper domains). Definition of the full molecular landscape awaits extensive whole exome sequencing, although GATA2 mutations (targeting the Zinc Finger 1, ZF1, domain) have been reported in 20-40% of sporadic CEBPAdm AML and recent targeted resequencing analysis revealed a further association with WT1 mutations. With minimal clinical and molecular information available for familial CEBPA-AML, we are often consulted regarding the management of this unique patient population. To address this need, we have investigated a multi-centre cohort of families with germline CEBPA mutations, providing extended clinical follow up, whole exome profiling of secondary mutations and molecular analysis of relapsed disease.

  Study EGAS00001000949

• The Druze analysis group

  To comprehensively characterize the genetic structure of the Druze population, we recruited and genotyped 40 parent-offspring trios from the Upper Galilee in Israel and the Golan Heights, attempting to capture different extended families (clans) across various geographical locations.

  Study EGAS00001000963

• Recent genetic history of Denmark

  The "Where Are You From?" project explores the extent to which recent and more distant historical events left their mark on the genetic structure of the current Danish population. The project's ultimate goal is to gain insights into the historical complexity of Denmark from the genetic perspective. To this goal, a data set consisting of approximately 800 high school students from across Denmark was used to run an extensive genetic analysis.

  Study EGAS00001001868

• Exome and RNA sequencing of relapsed TCF3-PBX1 t(1;19) acute lymphoblastic leukemia

  TCF3-PBX1 (E2A-PBX1) is a recurrent gene fusion in B-cell precursor lymphoblastic leukemia (BCP-ALL), which is caused by the translocation t(1;19)(q23;p13). TCF3-PBX1 BCP-ALL patients typically benefit from chemotherapy; however, many relapse and subsequently develop resistant disease with few effective treatment options. Mechanisms driving disease progression and therapy resistance have not been studied in TCF3-PBX1 BCP-ALL. Here, we aimed to identify novel treatment options for TCF3-PBX1 BCP-ALL by profiling leukemia cells from a relapsed patient, and determine molecular mechanisms underlying disease pathogenesis and progression. By drug sensitivity testing of leukemic blasts from the index patient, control samples and TCF3-PBX1 positive and negative BCP-ALL cell lines, we identified the phosphatidylinositide 3-kinase delta (p110δ) inhibitor idelalisib as an effective treatment for TCF3-PBX1 BCP-ALL. This was further supported by evidence showing TCF3-PBX1 directly regulates expression of PIK3CD, the gene encoding p110δ. Other somatic mutations to TP53 and MTOR, as well as aberrant expression of CXCR4, may influence additional drug sensitivities specific to the index patient and accompanied progression of the disease. Our results suggest that idelalisib is a promising treatment option for patients with TCF3-PBX1 BCP-ALL while other drugs could be useful depending on the genetic context of individual patients.

  Study EGAS00001001876

• Genetic landscape of malignant peripheral nerve sheath tumors

  Neurofibromatosis 1 is a hereditary syndrome characterized by the development of numerous benign neurofibromas, a small subset of which progress to malignant peripheral nerve sheath tumors (MPNSTs). To better understand the genetic basis for MPNSTs, we performed whole genome sequencing on four MPNSTs from patients with neurofibromatosis 1 and found that each of them had a somatic, inactivating mutation of SUZ12, a chromatin modifying gene adjacent to the NF1 gene responsible for the benign neurofibromas in these patients. We then performed targeted sequencing on an additional 46 MPNSTs and found that 12 had somatic mutations in SUZ12. Fifteen of the 17 (88%) mutations in SUZ12 were predicted to inactivate protein function, implicating it as a tumor suppressor gene possibly responsible for the progression from neurofibromas to MPNTs.

  Study EGAS00001000974

• Frequent alterations in cytoskeleton remodeling genes in primary and metastatic Chinese lung adenocarcinomas

  The landscape of genetic alterations in lung adenocarcinoma derived from Asian patients is largely uncharacterized. Here we present an integrated genomic and transcriptomic analysis of 335 primary lung adenocarcinomas and 35 corresponding lymph node metastases from Chinese patients. Altogether 13 significantly mutated genes are identified, including themost commonly mutated gene TP53 and novel mutation targets such as RHPN2, GLI3 and MRC2. TP53 mutations are furthermore significantly enriched in tumours from patients harbouring metastases. Genes regulating cytoskeleton remodelling processes are also frequently altered, especially in metastatic samples, of which the high expression level of IQGAP3 is identified as a marker for poor prognosis. Our study represents the first large-scalesequencing effort on lung adenocarcinoma in Asian patients and provides a comprehensive mutational landscape for both primary and metastatic tumours. This may thus form a basis for personalized medical care and shed light on the molecular pathogenesis of metastatic lung adenocarcinoma.

  Study EGAS00001000982

• McGill Epigenomics Mapping Centre

  The McGill Epigenomics Mapping Centre (EMC) and Data Coordination Centre (EDCC) were established in 2012 at the McGill University and Genome Quebec Innovation Centre (Montreal, Canada) to support large-scale human epigenome mapping for a broad spectrum of cell types and diseases. Previous epigenetic studies have provided profiles of specific chromatin marks in relation to basic biological processes, and future studies of molecular mechanisms must build upon these proofs-of-concept by integrating sequence-based variation with multiple levels of epigenetic and transcriptional regulation across the genome of human tissues and animal disease models. This project leverages the high-throughput sequencing infrastructure and expertise in genomics and transcriptomics at the McGill Innovation Centre to carry out this research. Controlled access to the data by collaborators and the greater scientific community is gained via a portal, which takes advantage of Compute Canada high-performance computing cluster resources to manage the large volume of data associated from the generation of reference epigenome maps. McGill University is one of two Canadian mapping and data coordination centres, the other based at the Michael Smith Genome Sciences Centre in Vancouver, British Columbia. The generation of comprehensive epigenome maps at McGill University is part of a larger international effort that is coordinated by the International Human Epigenome Consortium (IHEC), whose overall long-term objective is to determine the extent to which the epigenome shapes human populations over generations and in response to the environment. This project is funded under the Canadian Epigenetics, Environment, and Health Research Consortium (CEEHRC) by the Canadian Institutes of Health Research and by Genome Quebec, with additional support from Genome Canada. The computing and networking infrastructure, and part of the software development, are provided by Compute Canada and CANARIE.

  Study EGAS00001000995

• MutWP1__CRUK_Grand_Challenge_Mutographs_of_Cancer__Colorectal

  he Mutographs project aims to advance our understanding of the causes of cancer through studies of mutational signatures. Led by Mike Stratton, together with Paul Brennan, Ludmil Alexandrov, Allan Balmain, David Phillips and Peter Campbell, this large-scale international research endeavour was awarded a Cancer Research UK Grand Challenge. Different patterns of somatic mutation are generated by the different environmental, lifestyle and genetic factors that cause cancer, many of them are still unknown. Within Mutographs, the International Agency for Research on Cancer is coordinating the recruitment of 5000 individuals with cancer (colorectal, renal, pancreatic, oesophageal adenocarcinoma or oesophageal squamous cancers) across 5 continents to explore whether different mutational signatures explain marked variation in incidence. In brief, through an international network of collaborators around the world, biological materials are collected, along with demographic, histological, clinical and questionnaire data. Whole genome sequences of tumour-germline DNA pairs are generated at the Wellcome Trust Sanger Institute. Somatic mutational signatures are subsequently extracted by non-negative matrix factorisation methods and correlated with risk factors data. Through an enhanced understanding of cancer aetiology, Mutographs unprecedented effort is anticipated to outline modifiable risk factors, lead to new approaches to prevent cancer, and provide opportunities to empower early detection, refine high-risk groups and contribute to further therapeutic development.

  Study EGAS00001003774