22938 results for "ega"

in 106.03 milliseconds.

• scRNA-seq of patient-derived PDAC organoids and matched CAFs

  We established direct three-dimensional (3D) co-cultures of primary PDAC organoids and patient-matched CAFs. Single-cell RNA sequencing was performed for three organoid/CAF pairs in mono- and co-culture to uncover transcriptional changes induced by tumor-stroma interaction. Single-cell RNA sequencing data evidenced induction of a pro-inflammatory phenotype in CAFs in co-cultures. Organoids showed increased expression of genes associated with epithelial-to-mesenchymal transition (EMT) in co-cultures and several potential receptor-ligand interactions related to EMT were identified, supporting a key role of CAF-driven induction of EMT in PDAC chemoresistance.

  Study EGAS00001006661

• The molecular landscape of glioma in patients with Neurofibromatosis 1.

  Neurofibromatosis type 1 (NF1) is a common tumor predisposition syndrome in which glioma is one of the most prominent tumor type. Gliomagenesis in NF1 results in heterogeneous spectrum of tumors, from low grade to high grade glioma, occurring during the entire patient lifespan. In this study, we present the molecular landscape of low- and high-grade glioma in children and adults affected by NF1 (NF1-glioma). 59 tumor samples from 56 NF1-glioma patients with 43 matched normal were profiled with Whole Exome Sequencing, DNA Methylation array (31 tumors) and RNA sequencing (29 tumors).

  Study EGAS00001003186

• scRNAseq and scATACseq of placebo controlled-trial on MMR non-specific effects

  The project includes sequencing data of isolated PBMCs extracted from donors that received the MMR vaccine and donors that received placebo, both containg samples before and after the vaccine. In total, 6 MMR-vaccinated and 6 Placebo donors for both timepoints were included in the scRNAseq data. In total, 12 MMR-vaccinated and 12 Placebo donors for both timepoints were included in the scATACseq data. The main goal of the project is studying the non-specific effects of the vaccine and its possible use as an inducer of trained immunity in vivo.

  Study EGAS00001006787

• Spatial and temporal intra-tumoural heterogeneity in advanced High-Grade Serous Ovarian Cancer: implications for surgical and clinical outcomes

  Limited evidence exists on the extent and impact of spatial and temporal heterogeneity of high grade serous ovarian cancer (HGSOC) on tumour evolution and patients surgical and clinical outcome. We investigated this through systematic mapping of multi-site tumours at initial presentation and matched relapse from 49 chemo-naïve HGSOC patients with high tumour load, operated upfront. Our data provides a unique insight into the tumour evolution and metastatic pathways of HGSOC across time and space, how this complexity relates to surgical and clinical outcome and its consequences on clinical decision-making.

  Study EGAS00001007164

• AML FLT3 TCR study

  We identified a T-cell receptor (TCR) reactive to the recurrent FLT3 D835Y mutation in the tyrosine-kinase domain frequently expressed in acute myeloid leukemia (AML). To validate the TCRs' elimination efficacy of leukemic cells, we transplanted human AML cells with FLT3 D835Y mutation into NSG-SGM3 mice and treated either with TCR FLT3 D835Y redirected T cells, or control TCR (TCR 1G4). After treatment, we performed flow sorting of human AML cells from the mice (mCD45-hCD45+hCD3-hCD19-) and compared to primary AML blasts (hCD3-hCD19-) and primary T cells (hCD3+hCD8+orhCD4+hCD19-hCD33-) by whole-exome sequencing.

  Study EGAS00001007467

• Non-invasive prenatal diagnosis by genome-wide haplotyping of maternal cell-free plasma DNA

  Whereas non-invasive prenatal testing for aneuploidies (NIPT-A) is widely implemented, non-invasive prenatal testing for monogenic diseases (NIPT-M) is lagging. By capturing and targeted sequencing of 250000 polymorphic SNP loci from maternal plasma circulating cell-free DNA (cfDNA) and DNA from relatives, the fetal haplotype and chromosomal copy numbers are deduced. In all families tested, the cfDNA derived haplotypes are on average 97% concordant with the neonatal and embryo haplotype. This generic non-invasive prenatal diagnostic approach allows cost efficient scrutinizing the fetal genome for the presence of any inherited monogenic disease or trait.

  Study EGAS00001003634

• Whole genome and whole transcriptome sequencing of patients diagnosed with angiosarcoma.

  Angiosarcomas are rare, clinically-aggressive tumors with a predilection for the elderly and immunosuppressed, which has incited suspicion of an oncogenic virus. We studied the metagenomic landscape of angiosarcomas and identified reads mapping to human herpesvirus-7 (HHV-7). Overall, HHV-7 was present in two-thirds of angiosarcomas, particularly in cases with low tumor mutation burden and lacking signatures of ultraviolet-induced DNA damage. Transcriptomic profiling revealed the enrichment of tumor inflammation signatures in HHV7-positive angiosarcomas. In conclusion, we identified a distinct “inflammatory” subtype of angiosarcoma associated with HHV-7.

  Study EGAS00001003895

• Mutation signatures in melanocytic nevi reveal characteristics of defective DNA repair

  Nevi are common benign melanocytic neoplasms that can be found on any skin location and share many of the genomic hallmarks of melanoma. In our recent report involving whole-exome sequencing of acquired nevi (Stark et al., 2018), ultra-violet radiation (UVR) related somatic mutation signatures (“signature 7”) (Alexandrov et al., 2013) were frequently observed in all lesions that were located on sun-exposed sites. In the study presented herein, we sought to investigate whether an independent Spanish cohort (Valencia, Spain) of minimally sun exposed nevi had genomic features consistent with our previous findings.

  Study EGAS00001004274

• Human Developmental Biology Resource (HDBR) abnormal fetal samples

  The HDBR (www.hdbr.org) is a human embryonic and fetal tissue bank supplying registered researchers with access to these valuable research materials up to 22 weeks post-conception (PMC4640175). All of the samples collected are analysed for chromosomal abnormalities, and all samples with an abnormal phenotype are either analysed by SNP array, or exome sequenced. This dataset is generated from those abnormal samples that have been analysed by exome sequencing. To request access to this dataset, or if any researcher is interested in obtaining tissue from any of the samples HDBR collect, please email enquiries@hdbr.org.

  Study EGAS00001006300

• Whole transcriptome sequencing of chemotherapy-resistant muscle-invasive urothelial bladder cancer

  All mRNA sequencing data were acquired from single patients (BC159T) at a different time (BC159-T#1, BC159-T#2, and BC159-T#3). The first transurethral resection of bladder tumor (TUR-BT) (BC159-T#1) was diagnosed with non-MIUBC (muscle-invasive urothelial bladder cancer). Despite of intravesical bacillus Calmette-Guerin (BCG), the patient progressed into MIUBC at the second TUR-BT (BC159-T#2). After undergoing multiple neoadjuvant chemotherapy regimens (gemcitabine/paclitaxel and sequential paclitaxel), the patient developed local recurrence and multiple lung metastases and removed following palliative partial cystectomy (BC159-T#3).

  Study EGAS00001004232

• Molecular profiling of EBV associated diffuse large B-cell lymphoma

  We describe distinct molecular mechanisms leading to recurrent activation of JAK-STAT signaling, perturbation of epigenetic regulators as well as other direct targetable alterations such as PD-L1 amplification and overexpression contributing to immune evasion of lymphoma cells. Using the LymphGen 2.0 classifier, we combine data of recurrent mutations, somatic copy number alterations, and structural variants in an integrative analysis . For the first time, we reveal that less than 20% of primary EBV+ DLBCLs can be attributed to established molecular clusters of DLBCL NOS emphasizing the unique molecular character of this disease.

  Study EGAS00001006400

• Multiple Tissue Monitoring in Huntington disease - RNAseq skeletal muscle

  We examined whether peripheral tissues can serve as a source of readily accessible biological signatures at the RNA and protein level in Huntington disease (HD) patients. Under the MTM-HD study we generated large, high-quality human datasets from skeletal muscle, skin and adipose tissue, as well as primary human fibroblast lines to probe molecular changes in human pre-manifest and early manifest HD patients. We document the involvement of inflammation, energy metabolism and extracellular vesicle homeostasis. This demonstrates the potential to identify biological signatures from peripheral tissues in HD suitable as biomarkers in clinical trials.

  Study EGAS00001006474

• Alternative lengthening of telomeres in childhood neuroblastoma from genome to proteome

  Telomere maintenance by telomerase activation or alternative lengthening of telomeres (ALT) is a major determinant of poor outcome in neuroblastoma. Here, we screen for ALT in primary and relapsed neuroblastomas and characterize its features using multi-omics profiling. We aim to deepen the knowledge about the biology and clinical features of ALT-positive neuroblastomas by enriching ALT tumors in the study cohort independent of ATRX mutation status. Using a combination of genomic, transcriptomic and proteomic profiling, we provide evidence that this subgroup is clinically and molecularly distinct.

  Study EGAS00001004349

• 502 present-day genotypes included in the '137 ancient human genomes from across the Eurasian steppe' publication

  For thousands of years, the Eurasian steppe has been a centre for human migrations and cultural changes. To understand its population history following the Bronze Age migrations, 137 ancient humans were sequenced. These ancient DNA sequences were notably compared to the genetic data of present-day populations from Eurasia. Besides already published data, 502 individuals currently living in Inner Asia and Jordania were sampled and newly genotyped on diverse DNA-arrays. These new data, merged as a single dataset of 242,406 autosomal SNPs, are included in the present ENA study.

  Study EGAS00001002926

• 503 genotypes from Inner Asia used in 'Close inbreeding and low genetic diversity in Inner Asian human populations despite geographical exogamy' publication

  Inner Asia is particularly interesting to understand human history and evolution, as two groups presenting contrasting cultural traits (notably their language, their social organisation and matrimonial system) cohabit. We sampled 503 individuals from these two groups, belonging to 17 populations from 11 distinct ethnic groups (AltaiKizhi, Kazakh, Khakas, Kyrgyz, Mongolian, Shore, Tajik, Telengit, Tubalar, Turkmen and Uzbek). The samples were then genotyped with 5 different DNA-arrays and, after quality-control, the 253,532 autosomal SNPs present in all the arrays were merged together in the present dataset.

  Study EGAS00001002951

• The exomic landscape of t(14,18) negative diffuse follicular lymphoma with 1p36 deletion

  t(14,18) negative diffuse follicular lymphoma with 1p36 deletion is a well characterized variant of follicular lymphoma with typical clinical, morphological, immunophenotypical and genetic features. The genetic landscape of this variant is however largely unknown. We performed exome sequencing of six well characterised cases and detected 1642 single nucleotide variations and 641 insertions-deletions not reported in common databases (dbSNP and 1000G). We report several recurrent mutations, among which CREBBP, STAT6, KMT2D, HEATR6, LAMA5 and VPS13B are the most prevalent. Pathway annotation using GSEA showed an enrichment in mutated genes belonging to the MAPK pathway.

  Study EGAS00001002594

• Genetic determinants of glycated hemoglobin levels in the Greenlandic Inuit population

  We recently showed that a common genetic variant leads to a remarkably increased risk of type 2 diabetes (T2D) in the small and historically isolated Greenlandic population. Motivated by this, we aimed at investigating the genetic determinants for glycated hemoglobin (HbA1C). We found no novel associations but saw that for 10 out of 15 known HbA1C loci that the effects in Greenlandic Inuit were similar to previously reported. One locus, ANK1, showed a significant ancestral population specific effect. Our results shed light on the genetics effects across ethnicites.

  Study EGAS00001002641

• Natural variation of circulating RNAs in human serum

  Non-coding RNA (ncRNA) molecules have fundamental roles in cells and many are also stable in body fluids as extracellular RNAs. In these studies, we used RNA sequencing (RNA-seq) to investigate the profile of small non-coding RNA (sncRNA) in human serum. We analyzed more than 10 billion Illumina reads from more than 500 serum samples, included in the Norwegian population-based Janus Serum Bank (JSB). Our results suggest that many circulating RNAs in serum can be potential biomarkers and they are associated with different traits including age, sex, smoking, body size etc.

  Study EGAS00001002814

• Ibrutinib induces a global chromatin reorganisation in chronic lymphocytic leukaemia

  Chronic lymphocytic leukaemia (CLL) is the most common haematological malignancy in developed countries. Ibrutinib (PCI-32765), a specific and irreversible inhibitor of Bruton's Tyrosine Kinase (BTK) represents a major step forward in the treatment of CLL. We have undertaken a detailed analysis of the changes happening to the chromatin structure in CLL cells from patients continuously receiving oral doses of ibrutinib. ChIP-seq has been performed for H3K4me3, H3K27ac, H3K27me3 and EZH2 . We observed that Ibrutinib-dependent lymphocytosis correlates with a global and transient recruitment of EZH2 to active cis-regulatory elements and increased H3K27me3.

  Study EGAS00001002827

• CCND1-negative MCL

  A subset of CCND1-negative mantle cell lymphoma MCL (CCND1- MCL) has been recognized, and around half of them harbor CCND2 translocations. To identify other potential mechanisms driving MCL pathogenesis we investigated CCND1− MCL by by whole genome/exome sequencing. We identified a cryptic insertion of IGK and IGL enhancer regions near the CCND3 gene in three cases. Specific FISH probes detected 10 additional cryptic IGK juxtapositions to CCND3 (6 cases) and CCND2 (4 cases). In conclusion, virtually all CCND1-/SOX11+ MCL carry CCND2/CCND3 rearrangement with IG genes, including cryptic IGK/L enhancer regions not detected with currently used FISH probes.

  Study EGAS00001003060

• Primary breast cancers and paired brain metastases sequencing study

  Improving management of brain metastases (BM) from primary breast cancer (PBC) is a challenge in which targeted therapies play a promising role. However this approach is impaired by miss-knowledge of molecular patterns of the metastatic and drug-resistance processes.We performed a differential analysis of copy-number-alterations (CNAs) and mutations profiles by using pan-genomic array-CGH and targeted next-generation-sequencing of 494 cancer-associated genes, in a series of 14 pairs of matched PBC/BM and assessed if the observed genomic alterations may be used as a druggable agent in a clinical trial.

  Study EGAS00001003173

• Microsatellite unstable colorectal cancers

  Immune escape has been recognised as one of the hallmarks of cancer. Overcoming this immunomodulatory process by tumour cells has become a major therapeutic target. Here we utilize organoid technology to study immune-cancer interactions and assess immunomodulation by colorectal cancer (CRC). Transcriptional profiling and flow cytometry revealed that organoids maintain differential expression of immunomodulatory molecules present in primary tumours. Finally, we established a method to model antigen-specific epithelial cell killing and cancer immunomodulation in vitro using CRC organoids co-cultured with cytotoxic T cells. Our method may serve as a first step to rebuilding the tumor microenvironment in vitro.

  Study EGAS00001003366

• Pancreatic cancer organoids recapitulate disease and allow personalized drug screening

  We report derivation of 30 Patient-Derived Organoid lines (PDOs) from tumors arising in the pancreas and distal bile duct. PDOs recapitulate tumor histology and contain genetic alterations typical for pancreatic cancer. In vitro testing of a panel of 76 therapeutic agents revealed sensitivities currently not exploited in the clinic. The PRMT5 inhibitor EZP015556, shown to target MTAP negative tumors, was validated as such, but also appeared to constitute an effective therapy for a subset of MTAP+ tumors. Taken together, the work presented here provides a platform to identify novel therapeutics to target pancreatic tumor cells using PDOs.

  Study EGAS00001003369

• COMPARE study: participants typed during UK Biobank version 2 array development phase

  The COMPARE study enrolled 29,066 British blood between donors between February 2016 and March 2017, the study aim is to find the optimum technology for haemoglobin screening (ISRCTN 90871183). All participants were at the time of recruitment active blood donors. The 4,796 participants in this dataset have consented to join the NIHR BioResource. Genotyping data was produced using the Thermo Fisher Scientific Axiom Genotyping platform. The UK Biobank version 2 array design was used, content on this array has been added to allow for accurate DNA based identification of human blood group antigens.

  Study EGAS00001003748

• Chracterising_cellur_pathways_underlying_CD3_CD28_activation_of_human_CD4__cells

  We devised an approach to disentangle the TCR and CD28 pathways upon stimulation in naive and memory primary human CD4+ T cells (Tcons) in response to defined stimulatory signals. Isolated memory and naïve T cells were activated using anti-CD3, anti-CD28 or both in combination. As a control we cultured cells in the same conditions but without the stimuli. We carried Chipmentation using the H3K27ac antibody on 200,000 cross-linked cells. 1) 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 please see http://www.sanger.ac.uk/datasharing/

  Study EGAS00001002599

• T-cell reconstitution after reduced dose ATLG induction in kidney transplant recipients

  Pre-sensitized kidney transplant recipients have a higher risk for rejection following kidney transplantation and therefore receive a lymphodepletional induction therapy with anti human T-lymphocyte globulin (ATLG). The time course of lymphocyte reconstitution with regards to overall and donor-reactive T-cell receptor (TCR) specificity remains elusive. In this study we aimed to describe the TCR repertoire in a reduced dose ATLG regimen making it possible to evaluate shifts in the shape of the immune repertoire and to detect the reappearance of donor-reactive T-cells following reduced lymphodepletional induction therapy.

  Study EGAS00001005941

• Comprehensive genomic profiling of matched glioblastoma tumours, cell-lines, and xenografts reveals genomic stability and adaptation to disparate growth environments

  The mandate of this project was to use drug screening to deliver new drugs for glioblastoma (GBM) to clinical trials, and perform genomic assessment of GBM to discover new therapeutic targets and predictors of response. The sequencing data in this set was derived from GBM patient tumor samples, matched brain tumor initiating cells lines (BTICs), and tumor tissue derived from orthotopic implants.

  Study EGAS00001002709

• Single cell transcriptomic and genomic profiling of carcinogenesis in patients with familial adenomatous polyposis

  Familial Adenomatous Polyposis (FAP) is characterized by hundreds to thousands of adenocarcinomas at different evolutional stages in the colon and rectum. Much effort has been made to illuminate the key genomic alterations that facilitate the transition from adenoma to carcinoma. However, the strong heterogeneity of the tumors may hamper these efforts. Here, by sequencing matched adjacent normal tissues, adenomas at different stages and carcinomas from the same patient, we precisely traced the process of colorectal carcinogenesis. Our study offers an accurate genomic landscape during the initiation and progression of carcinogenesis, especially for the transition between adenomas and carcinomas.

  Study EGAS00001003598

• WXS of 147 lung cancer patients treated with immunotherapy

  We first attempted to predict MHC-binding neoantigens at high accuracy with convolutional neural networks. This prediction model outperformed previous methods in > 70% of test cases. Importantly, our method remarkably increased the predictive value of neoantigen load especially in combination with known resistance parameters. We then developed a classifier that can predict resistance from point mutations that are deleterious to protein function. Notably, genes involved in the adaptive immune response, cytokine signaling,and EGFR signaling held high explanatory power. Furthermore, when integrated with our neoantigen profiling, these anti-immunogenic mutations revealed significantly higher predictive power than known resistance factors.

  Study EGAS00001003781

• MutWP5__CRUK_Mutographs_of_Cancer__Lung__PD37920__Targeted_

  Sequencing of LCM-derived microbiopsies from explanted lung from COPD patient. Goal to assess the mutational burden, spectrum, and clonal dynamics within the tissue. Deep sampling throughout multiple regions of the lung will determine whether there are differences in smoking-related mutation burden in different portions of the lung. Targeted sequencing will be conducted on samples to identify drivers of interest and clonality of the samples, well-performing samples will be sent for subsequent whole-genome sequencing. Results from this portion of the study will be compared to other individuals with smoking-related diseases (COPD, pulmonary fibrosis, lung cancer), and normal, non-smoking lungs.

  Study EGAS00001003321

• Molecular profiling of blastic plasmacytoid dendritic cell neoplasm (BPDCN) as compared to acute myeloid leukemia (AML)

  Blastic plasmacytoid dendritic cell neoplasm (BPDCN) is a rare, male-predominant myeloid malignancy that is characterized by the malignant proliferation of precursor plasmacytoid dendritic cells (pDCs) with morphologic and molecular similarities to acute myeloid leukemia (AML) and myelodysplastic syndrome (MDS) in its presentation within the bone marrow and peripheral blood. To identify disease-specific molecular features of BPDCN, we profiled bone marrow, peripheral blood and serum samples from primary patient samples using an in-house hematologic malignancy panel (“T300” panel), transcriptome microarray, and serum multiplex immunoassays and compared results to a cohort of AML patients.

  Study EGAS00001003453

• Single-cell RNA-sequencing reveals that glioblastoma recapitulates a normal neurodevetlopmental hierarchy

  We discovered a conserved neural tri- lineage cancer hierarchy centered around glial progenitor-like cells. We also found that this progenitor population contains the majority of the cancer’s cycling cells, and, using RNA velocity, is often the originator of the other cell types. Finally, we show that this hierarchal map can be used to identify therapeutic targets specific to progenitor cancer stem cells. Our analyses show that normal brain development reconciles glioblastoma development, suggests a possible origin for glioblastoma hierarchy, and helps to identify cancer stem cell-specific targets.

  Study EGAS00001004422

• Characterization of four subtypes in morphologically normal tissue excised proximal and distal to breast cancer

  Our study provides insight into molecular alterations in HN tissues within the affected breast and offers a greater understanding of the spatial implications of these aberrations. This was achieved by performing a comprehensive analysis of RNA sequencing data and proteomic profiles from breast cancers (n=19) and their matched HN tissues (n=38), healthy breast from cosmetic reduction mammoplasty (RM; n=5), and risk reducing mastectomies (RR, n=5), with peritumoral samples excised at proximal (TP, <2 cm) and distal (TD, 5-10 cm) sites from the primary tumor.

  Study EGAS00001004510

• Transcriptomic analysis of the Phase 3 COMPARZ clinical trial

  Metastasis remains the main reason for renal cell carcinoma (RCC)-associated mortality. Tyrosine kinase inhibitors (TKI) impart clinical benefit for most RCC patients but the determinants of response are poorly understood. We report an integrated genomic and transcriptomic analysis of metastatic clear cell RCC (ccRCC) patients treated with TKI therapy and identify predictors of response. Patients in the COMPARZ phase III trial received first-line sunitinib or pazopanib with comparable efficacy. Microarray-based transcriptomic analyses with results from Next-gen genomic analyses of targeted genes revealed distinct molecular subgroups associated with response and survival.

  Study EGAS00001004534

• Whole Genome Sequencing of 317 individuals from the Pacific region

  Although genetic studies of modern Oceanians have revealed varying levels of admixture with populations of East Asian ancestry, attributed to the Austronesian expansion, the early peopling history of Oceania remains poorly characterized. Additionally, it is currently unknown whether and how the settlement of the Pacific was accompanied by genetic adaptation to island environments, and if archaic introgression facilitated this process in Oceanians, who present the highest worldwide levels of combined Neanderthal and Denisovan ancestry. This study reports the first whole genome-based survey that addresses a wide range of questions related to the demographic and adaptive history of Pacific populations.

  Study EGAS00001004540

• Indonesian Genome Diversity Project 2

  High-coverage whole genome sequences were collected to study patterns of genomic variation across the broad geography of Indonesia and New Guinea. This region has experienced an extremely complex demographic history, including repeated bouts of admixture with archaic and modern human groups. This dataset reports whole genome sequences for 82 individuals from different populations from Mentawai, New Guinea, Sumatra and Sumba islands. Particular attention has been paid in the original study to genomic signals that are informative for population history, including admixture with archaic hominins and the role of modern human admixture during the late Pleistocene and Holocene.

  Study EGAS00001003654

• Ultraviolet radiation drives mutations in a subset of mucosal melanomas

  Although identified as the key environmental driver of common cutaneous melanoma, the role of ultraviolet radiation (UVR)-induced DNA damage in mucosal melanoma is poorly defined. We present the largest cohort of mucosal melanomas of conjunctival origin to be analyzed by whole genome sequencing and show a predominance of UVR-associated single base substitution signature 7 (SBS7) in the majority of the samples. Our data shows mucosal melanomas with SBS7 dominance have similar genomic patterns to cutaneous melanomas and therefore this subset could benefit from treatments currently used for common cutaneous melanoma.

  Study EGAS00001004697

• Genomics_of_acral_lentiginous_melanoma

  Melanoma is the most aggressive type of skin cancer, causing about 75% of dermatological cancer deaths. Acral lentiginous melanoma (ALM) is the most common subtype of melanoma in admixed Latin American populations, but very few tumour genomes and exomes, all from European-descent individuals, have been analysed across several studies. Because of this, the genomic landscape of ALM is mostly unknown. Our aim in this project is to define this landscape and identify driver somatic alterations by whole-exome sequencing a collection of ALM germline/tumour paired FFPE samples from the National Cancer Institute of Mexico.

  Study EGAS00001003740

• HCA_Female_Reproductive_Adult_WSSS_RNA

  HCA Endometrium_LM The endometrium regenerates monthly and its transformation is executed through dynamic changes in states and interactions of multiple cell types. Using transcriptomics methods we seek to profile changes of the endometrium across the menstrual cycle. Our map will have implications in women’s health and cancer, by enabling the interpretation of GWAS analyses or the studying functional consequences of somatic mutations. 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/

  Study EGAS00001004727

• NRG1 Fusions in KRAS Wild-type Pancreatic Cancer (H021)

  We used whole-genome and transcriptome sequencing to identify clinically actionable gene fusions in young adults with KRAS wild-type (KRASwt) pancreatic ductal adenocarcinoma (PDAC). These alterations included recurrent NRG1 rearrangements predicted to drive PDAC development through aberrant ERBB receptor-mediated signaling, and pharmacologic ERBB inhibition resulted in clinical improvement and remission of liver metastases in two patients with NRG1-rearranged tumors that had proved resistant to standard treatment. Our findings demonstrate that systematic screening of KRASwt tumors for oncogenic fusion genes will substantially improve the therapeutic prospects for a sizeable fraction of PDAC patients.

  Study EGAS00001002759

• Genomics_of_acral_lentiginous_melanoma___RNAseq

  Melanoma is the most aggressive type of skin cancer, causing about 75% of dermatological cancer deaths. Acral lentiginous melanoma (ALM) is the most common subtype of melanoma in admixed Latin American populations, but very few tumour genomes and exomes, all from European-descent individuals, have been analysed across several studies. Because of this, the genomic landscape of ALM is mostly unknown. Our aim in this project is to define this landscape and identify driver somatic alterations by whole-exome sequencing a collection of ALM germline/tumour paired FFPE samples from the National Cancer Institute of Mexico.

  Study EGAS00001003758

• Single cell T cell Landscape and T Cell Receptor Repertoire Profiling of AML in Context of PD-1 Blockade Therapy

  Eight pretreatment and 14 posttreatment bone marrow (BM) aspirates from 8 patients with R/R AML treated with azacitidine and nivolumab along with 2 control BM from healthy donors were profiled with scRNA sequencing with matching scTCR -, scBCR - and scATAC sequencing. Additionally, the targeted DNA sequencing in at least 1 time point per patient (total evaluated 17/22 samples, two samples were performed using CLIA-certified molecular diagnostic assay and data is not available) was performed. The Fastq files and/or bam files are available in this dataset.

  Study EGAS00001004894

• Transcriptome sequencing of intravenous leiomyomatosis and uterine myoma

  Up to now, there are two hypothesis about the pathogenesis of the relationship of intravenous leiomyomatosis and uterine myoma. One theory suggests that the IVL comes from the smooth muscle cell in the vessel wall.The other theory indicates that the IVL derives from the uterine myometrium. However, limited to the technology, few studies have been deeply explore the underlying relation. In this study, we employ the RNA sequencing to explore the molecule relationship between IVL and uterus myoma. In order to identify the molecule relationship between IVl and uterine myoma we conducted transcriptome sequencing and bioinformaitc analysis

  Study EGAS00001002504

• The aim of this study was to identify underlying hub genes and dysregulated pathways associated with the development of HCC using bioinformatics analysis.

  In the present study, we identified differentially expressed protein-coding genes from RNA transcriptional profiling performed on 11 paired cancer tissues and adjacent non-cancerous tissues. Then, we conducted GO, KEGG, PPI network and centralities analyses to study and identify changes in pathways and hub genes. The aim of this study was to improve understanding of HCC carcinogenesis by providing information concerning the genetic changes that occur during disease progression and to uncover the expression of biomarkers with potential use for clinical diagnosis, treatment, and monitoring of disease progression.

  Study EGAS00001002526

• Progression to AML is predictable and distinct from age related clonal hematopoiesis

  To examine the occurrence of somatic mutations prior to the development of acute myeloid leukemia, we undertook deep ECS (estimated limit of detection 1 mutation in 2500 cells) of 261 AML associated genes in 96 pre-AML cases and 420 age and gender-matched healthy controls of an average of 3853 unique DNA molecules covering each of the 1.19M bases spanning the target gene panel. The findings suggest that the development of clonal hematopoiesis and accumulation of somatic mutations is distinct and accelerated in pre-AML cases compared to healthy individuals

  Study EGAS00001002570

• NanoSring of PBMC from bladder cancer and RCC patients

  PBMCs from patients were isolated using 50 mL Leucosep™ tubes (Greiner Bio-One International, Germany) and Ficoll-Paque™ PLUS (GE Healthcare, Sweden). Whole blood drawn into sodium heparin blood collection tubes were diluted 3x with phosphate-buffered saline (PBS) without calcium or magnesium (Lonza, Walkersville, MD). Diluted cell suspensions were carefully layered on Leucosep tubes and centrifuged for 15 minutes at 800 x g at room temperature (RT). Interphase containing PBMCs were harvested and washed with PBS and subsequently centrifuged for 10 minutes at 250 x g at RT before further processing.

  Study EGAS00001004229

• Transcriptome profiling of human plucked frontal and occipital hair follicles

  Androgenetic alopecia (AGA) is characterized by a progressive and androgen-dependent loss of hair from the frontal and vertex regions of the scalp. Although large-scale genetic analyses have identified >300 genetic risk factors, the underlying causal genes and pathways, and their involvement in core pathophysiological mechanisms, remain unclear. In the present study, systematic profiling of differential mRNA and microRNA expression was performed in human hair follicle samples from frontal and occipital scalp regions. Taken together, the present data improve understanding of the genomic regions, genes, and pathways that are implicated in AGA pathobiology.

  Study EGAS00001002832

• Exploring_the_heterogeneity_of_sarcoma_using_single_cell_sequencing_

  Multi region samples are collected from patients, with consent, immediately after resection of the tumour. Samples are digested and sorted using FACS as single cells into lysis buffer. Cells are then stored until further processing for G&T-seq. After sequencing, we will explore intra-tumour heterogeneity using computational approaches to integrate RNA and DNA data onto the tumour phylogeny 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/

  Study EGAS00001002866

• Identification of hypermutation and defective mismatch repair in ctDNA from metastatic prostate cancer

  DNA mismatch repair defects (MMRd) and tumor hypermutation are rare and under-characterized in metastatic prostate cancer. Furthermore, since hypermutated MMRd prostate cancers can respond to immune checkpoint inhibitors, there is an urgent need for practical detection tools. We analyzed cell-free DNA targeted sequencing data from 434 metastatic prostate cancer patients with circulating tumor DNA (ctDNA) purity above 2%. Samples with somatic hypermutation were subjected to 150x whole exome sequencing. These data allowed us to interrogate the salient genomic properties of this rare prostate cancer subtype and correlate findings with patient clinical outcomes.

  Study EGAS00001003899

• Single cell exome sequencing of lung adenocarcinoma

  Single cell exome sequencing was performed on 200 single cells isolated from a lung adenocarcinoma, female, non-smoker patient. The cells were derived from two distant tumour sectors and a far normal sector. The single cells were amplified on the Fluidigm C1 machine using the GE Healthcare illustra GenomiPhi V2 DNA Amplification Kit prior to sequencing library preparation. In addition, bulk exome sequencing was also conducted for each tumour sectors. For this study, somatic variations were detected from the single cells and phylogenetic clustering was conducted to elucidate the evolutionary trajectory of lung cancer.

  Study EGAS00001002972