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• Quantitative analysis of a novel DNA hypermethylation panel for lung cancer diagnosis using bronchial specimens

  Non-diagnostic findings in Transbronchial Lung Biopsy (TBLB) and Endobronchial Ultrasound-guided Transbronchial Lung Biopsy (EBUS-TBLB) are not uncommon. A challenge is to improve lung cancer detection by TBLB/EBUS-TBLB. In order to improve the diagnostic yield of bronchoscopy, we used 850K methylation chip to identify methylation sites that distinguish malignant from benign lung nodules.We found that the combination of HOXA7, SHOX2,and SCT methylation analysis has the best diagnostic yield in 123 bronchial washing (sensitivity: 74·1%; AUC: 0·851) and 172 brushing samples (sensitivity: 86·1%; AUC: 0·915). We developed a kit comprising these three genes and validated the kit in 329 unique bronchial washing samples, 397 unique brushing samples, and 179 unique patients with both washing and brushing samples. The diagnostic accuracy of the panel alone in lung cancer diagnosis was 86·9%, 91·2% and 95% in bronchial washing, brushing, and washing+brushing samples, respectively. The panel's sensitivity in combination with cytology, rapid on-site evaluation (ROSE), and histology in lung cancer diagnosis was 90·8% and 95.8% in bronchial washing and brushing samples, respectively, and 100% in washing+brushing samples. Quantitative analysis of the three-gene panel improves lung cancer diagnosis by bronchoscopy.

  Study EGAS00001007089

• Comprehensive genetic analysis of uveal melanoma heterogeneity during metastatic progression

  Uveal melanoma (UM) is the most common primary intraocular malignancy in adults. Despite improvement of diagnosis and treatment of the primary tumor, there is no effective treatment of metastatic disease and approximately half of patients will die within one year or less following metastases detection. Tumor heterogeneity has been proposed as a key factor of drug resistance. However, it has been scarcely studied in UM. The present project aims searching for specific drivers of the metastatic progression, describing the genomic and transcriptomic landscape of metastatic UM, exploring tumor heterogeneity and investigating its role in drug resistance. Thus whole exome sequencing and transcriptomics have been performed on constitutional, primary tumor and metastatic samples from 28 UM patients.

  Study EGAS00001002761

• sWGS data from 362 tumor with non muscle invasive bladder cancer and 30 blood samples (15 males and 15 females)

  A better understanding of the molecular landscape of non-muscle-invasive bladder cancer (NMIBC) is essential to improve risk assessment and identify potential therapeutic targets. Here, we perform a comprehensive genomic analysis of patients diagnosed with NMIBC based on whole-exome- (n=438), shallow whole-genome- (n=362), and total RNA-sequencing (n=414). This dataset contains 876 BAM files corresponding to the full WES dataset. This dataset contains 392 BAM files corresponding to the full sWGS dataset. Tumor samples were sequenced to median coverage of 2.14x (1.24-9.01).

  Dataset EGAD50000000732

• Whole-exome sequencing of 20 samples of actinic keratosis (10s) and cutaneous squamous cell carcinoma (10s)

  Whole-exome sequencing of 20 samples of actinic keratosis (10) and cutaneous squamous cell carcinoma (10) was performed to investigate a potential relationship between DNA methylation-based subtypes and genetic mutation patterns. 7 samples were shown to belong to the stem cell-like subclass (4 AK and 2 SCC), 12 - to the keratinocyte-like subtype (6 AK and 6 SCC) and one SCC sample is unclassified (was not included in the methylation analysis). Exome regions were captured using Agilent Low Input Exome-Seq Human v5 kit and sequenced on Illumina Hiseq4000 with paired-end 100-nucleotide reads.

  Dataset EGAD00001003765

• Genomic Evolution of Breast Cancer Metastasis and Relapse

  Recurrent breast cancer is almost universally fatal. We characterize 170 patients locally relapsed or distant metastatic cancers using massively parallel sequencing. We identify that the relapse-seeding clone disseminates late from the primary tumor. TP53 and AKT1 appear to be enriched in ER-positive cancers predisposed to relapse. Mutation acquisition continues at relapse as the same mutation signatures continue to operate and new signatures, such as that caused by radiotherapy appear de novo. In 49% of cases we identify drivers mutations private to the relapse and these are sampled from a wider range of cancer genes, including SWI-SNF complex and JAK-STAT signaling.

  Dataset EGAD00001002697

• Progress in Diabetes Genetics in Youth (ProDIGY) Exome Sequencing Study: SEARCH for Diabetes in Youth

  The ~52,000 sample Type 2 Diabetes Exome Sequencing project is a collaboration of six consortia with various funding mechanisms that have joined together to investigate genetic variants for type 2 diabetes (T2D) using the largest T2D case/control sample set compiled to date. This includes samples from: Type 2 Diabetes Genetic Exploration by Next-generation sequencing in multi-Ethnic Samples (T2D-GENES) Genetics of Type 2 Diabetes (GoT2D) Exome Sequencing Project (ESP) Slim Initiative in Genomic Medicine for the Americas (SIGMA) Lundbeck Foundation Centre for Applied Medical Genomics in Personalised Disease Prediction, Prevention, and Care (LuCAMP) Progress in Diabetes Genetics in Youth (ProDIGY) This data generated from the SEARCH for Diabetes in Youth cohort was part of the ProDIGY (Progress in Diabetes Genetics in Youth) consortium, which is a NIDDK-funded research consortium that investigated genetic variants for childhood type 2 diabetes (T2D). This consortium involved sequencing multiethnic samples from childhood T2D cases located across the United States. The individuals were obtained from over 20 cohorts across the 6 consortia that are listed in Table 1. The strategy was to perform deep exome sequencing of individuals, 24,991 with T2D and 24,953 controls, divided among five ancestry groups: Europeans, East Asians, South Asians, American Hispanics, and African Americans. The T2D-GENES, ProDIGY and SIGMA studies, sequencing was performed at the Broad Institute using the Agilent v2 capture reagent or Illumina Rapid Capture on Illumina HiSeq machines. Please note that while we summarize the full sample list in publications and below, two of the cohorts below are not in dbGAP, due to the samples not being consented for deposition. This includes the Kooperative Gesundheitsforschung in der Region Augsburg (KORA) study and Lundbeck Foundation Centre for Applied Medical Genomics in Personalised Disease Prediction, Prevention, and Care (LuCamp) study. The Exome Sequencing Project (ESP) was deposited in dbGAP as part of their initial study and the phs numbers for that project can be found here: https://esp.gs.washington.edu/drupal/dbGaP_Releases. Table 1. 52,000 sample T2D Case/Control Whole Exome Sequencing Studies table, th, td { border: 1px solid black; border-collapse: collapse; } Ancestry Consortia Study Countries of Origin # Cases # Controls African American T2D-GENES Project 1 Jackson Heart Study US 500 526 African American T2D-GENES Project 1 Wake Forest School of Medicine Study US 518 530 African American ESP Exome Sequencing Project (ESP) US 467 1374 African American T2D-GENES Follow up study BioMe Biobank Program (BioMe) US 1297 1256 East Asian T2D-GENES Project 1 Korea Association Research Project Korea 526 561 East Asian T2D-GENES Project 1& Follow up Study Singapore Diabetes Cohort Study; Singapore Prospective Study Program Singapore (Chinese) 1486 1568 East Asian T2D-GENES Follow up study Korea SNUH South Korea 450 475 East Asian T2D-GENES Follow up study Research Studies in Hong Kong (Hong Kong) Hong Kong 493 485 European T2D-GENES Project 1 Ashkenazi US, Israel 506 355 European T2D-GENES Project 1 Metabolic Syndrome in Men Study (METSIM) Finland 484 498 European GoT2D Finland-United States Investigation of NIDDM Genetics (FUSION) Study Finland 472 476 European GoT2D Kooperative Gesundheitsforschung in der Region Augsburg (KORA) Germany 97 90 European GoT2D UK Type 2 Diabetes Genetics Consortium (UKT2D) UK 322 320 European GoT2D Malmo-Botnia Study Finland, Sweden 478 443 European LuCamp Lundbeck Foundation Centre for Applied Medical Genomics in Personalised Disease Prediction, Prevention, and Care (LuCamp) Denmark 997 997 European ESP Exome Sequencing Project (ESP) US 390 2843 European T2D-GENES Follow up study Genetics of Diabetes and Audit Research Tayside Study (GoDARTS) Scotland, UK 960 966 European T2D-GENES Follow up study Framingham Heart Study (FHS) US 396 596 Hispanic T2D-GENES Project 1 San Antonio Family Heart Study, San Antonio Family Diabetes/ Gallbladder Study, Veterans Administration Genetic Epidemiology Study, and the Investigation of Nephropathy and Diabetes Study Family Component US 272 218 Hispanic T2D-GENES Project 1 & SIGMAv2 Starr County, Texas US 1762 1738 Hispanic SIGMAv1 Mexico City Diabetes Study Mexico 281 549 Hispanic SIGMAv1 & v2 Multiethnic Cohort (MEC) US 1476 1443 Hispanic SIGMAv1 & v2 UNAM/INCMNSZ Diabetes Study (UIDS) Mexico 1998 1977 Hispanic SIGMAv1 & v2 Diabetes in Mexico Study (DMS) Mexico 1522 1546 Multi ethnic ProDIGY Treatment Options for Type 2 Diabetes in Adolescents and Youth (TODAY) US 3097 0 Multi ethnic ProDIGY SEARCH for Diabetes in Youth (SEARCH) US 553 0 South Asian T2D-GENES Project 1 London Life Sciences Population Study (LOLIPOP) UK (Indian Asian) 551 538 South Asian T2D-GENES Project 1 & Follow up study Singapore Indian Eye Study Singapore (Indian Asian) 1640 1478 South Asian T2D-GENES Follow up study Pakistan Risk of Myocardial Infarction Study (PROMIS) Pakistan 914 932 The SEARCH study contributed 553 cases and 0 controls to 52k T2D exome sequencing study.

  Study phs001511

• Slim Initiative in Genomic Medicine for the Americas (SIGMA): Mexico City Diabetes Study (MCDS)

  The ~52,000 sample Type 2 Diabetes Exome Sequencing project is a collaboration of six consortia with various funding mechanisms that have joined together to investigate genetic variants for type 2 diabetes (T2D) using the largest T2D case/control sample set compiled to date. This includes samples from: Type 2 Diabetes Genetic Exploration by Next-generation sequencing in multi-Ethnic Samples (T2D-GENES) Genetics of Type 2 Diabetes (GoT2D) Exome Sequencing Project (ESP) Slim Initiative in Genomic Medicine for the Americas: Type 2 Diabetes (SIGMA T2D) Lundbeck Foundation Centre for Applied Medical Genomics in Personalised Disease Prediction, Prevention, and Care (LuCAMP) Progress in Diabetes Genetics in Youth (ProDIGY) This data generated from the SIGMA Mexico City Diabetes Study was part of the Slim Initiative in Genomic Medicine for the Americas: Type 2 Diabetes (SIGMA T2D), which is an international research consortium funded by the Carlos Slim Foundation that seeks to identify the genetic risk factors for type 2 diabetes (T2D) in Mexico and Latin America and translate those findings into improved treatment and prevention of diabetes. The SIGMA T2D project has sequenced and genotyped more than 13,000 samples from Mexican and Mexican Americans. The individuals were obtained from over 20 cohorts across the 6 consortia that are listed in Table 1. The strategy was to perform deep exome sequencing of individuals, 24,991 with T2D and 24,953 controls, divided among five ancestry groups: Europeans, East Asians, South Asians, American Hispanics, and African Americans. The T2D-GENES, ProDIGY and SIGMA studies, sequencing was performed at the Broad Institute using the Agilent v2 capture reagent or Illumina Rapid Capture on Illumina HiSeq machines. Please note that while we summarize the full sample list in publications and below, two of the cohorts below are not in dbGaP, due to the samples not being consented for deposition. This includes the Kooperative Gesundheitsforschung in der Region Augsburg (KORA) study and Lundbeck Foundation Centre for Applied Medical Genomics in Personalised Disease Prediction, Prevention, and Care (LuCamp) study. The Exome Sequencing Project (ESP) was deposited in dbGaP as part of their initial study and the phs numbers for that project can be found here: https://esp.gs.washington.edu/drupal/dbGaP_Releases Table 1. 52,000 sample T2D Case/Control Whole Exome Sequencing Studies Ancestry Consortia Study Countries of Origin # Cases # Controls African American T2D-GENES Project 1 Jackson Heart Study US 500 526 African American T2D-GENES Project 1 Wake Forest School of Medicine Study US 518 530 African American ESP Exome Sequencing Project (ESP) US 467 1374 African American T2D-GENES Follow up study BioMe Biobank Program (BioMe) US 1297 1256 East Asian T2D-GENES Project 1 Korea Association Research Project Korea 526 561 East Asian T2D-GENES Project 1& Follow up Study Singapore Diabetes Cohort Study; Singapore Prospective Study Program Singapore (Chinese) 1486 1568 East Asian T2D-GENES Follow up study Korea SNUH South Korea 450 475 East Asian T2D-GENES Follow up study Research Studies in Hong Kong (Hong Kong) Hong Kong 493 485 European T2D-GENES Project 1 Ashkenazi US, Israel 506 355 European T2D-GENES Project 1 Metabolic Syndrome in Men Study (METSIM) Finland 484 498 European GoT2D Finland-United States Investigation of NIDDM Genetics (FUSION) Study Finland 472 476 European GoT2D Kooperative Gesundheitsforschung in der Region Augsburg (KORA) Germany 97 90 European GoT2D UK Type 2 Diabetes Genetics Consortium (UKT2D) UK 322 320 European GoT2D Malmo-Botnia Study Finland, Sweden 478 443 European LuCamp Lundbeck Foundation Centre for Applied Medical Genomics in Personalised Disease Prediction, Prevention, and Care (LuCamp) Denmark 997 997 European ESP Exome Sequencing Project (ESP) US 390 2843 European T2D-GENES Follow up study Genetics of Diabetes and Audit Research Tayside Study (GoDARTS) Scotland, UK 960 966 European T2D-GENES Follow up study Framingham Heart Study (FHS) US 396 596 Hispanic T2D-GENES Project 1 San Antonio Family Heart Study, San Antonio Family Diabetes/ Gallbladder Study, Veterans Administration Genetic Epidemiology Study, and the Investigation of Nephropathy and Diabetes Study Family Component US 272 218 Hispanic T2D-GENES Project 1 & SIGMAv2 Starr County, Texas US 1762 1738 Hispanic SIGMAv1 Mexico City Diabetes Study Mexico 281 549 Hispanic SIGMAv1 & v2 Multiethnic Cohort (MEC) US 1476 1443 Hispanic SIGMAv1 & v2 UNAM/INCMNSZ Diabetes Study (UIDS) Mexico 1998 1977 Hispanic SIGMAv1 & v2 Diabetes in Mexico Study (DMS) Mexico 1522 1546 Multi ethnic ProDIGY Treatment Options for Type 2 Diabetes in Adolescents and Youth (TODAY) US 3097 0 Multi ethnic ProDIGY SEARCH for Diabetes in Youth (SEARCH) US 553 0 South Asian T2D-GENES Project 1 London Life Sciences Population Study (LOLIPOP) UK (Indian Asian) 531 538 South Asian T2D-GENES Project 1 & Follow up study Singapore Indian Eye Study Singapore (Indian Asian) 1640 1478 South Asian T2D-GENES Follow up study Pakistan Genomic Resource (PGR) Pakistan 914 932

  Study phs001375

• Sequencing of Coding and Non-coding Regions in Primary Breast Cancers and Patient-matched Controls

  Genomic analysis of tumor samples has led to the identification of hundreds of cancer genes based on the presence of mutations in protein-coding regions. By contrast, much less is known about cancer-causing mutations in non-coding regions. Here, we performed deep sequencing in 360 primary breast cancers and developed computational methods to identify significantly mutated promoters. Clear signals were found in the promoters of four genes. FOXA1, a known driver of hormone-receptor positive breast cancer, harbors a mutational hotspot in its promoter that leads to overexpression through increased E2F binding. RMRP and NEAT1, two non-coding RNA genes, carry mutations that alter protein binding to the promoter and impact expression levels. Overall, our study shows that recurrent mutations in or near gene promoters in cancers have functional consequences. Power analyses indicate that more such genes remain to be discovered through deep sequencing of adequately sized patient cohorts.

  Study phs001250

• A single-chain derivative of the integrin β1-activating TS2/16 antibody potentiates organoid growth in Matrigel and Collagen hydrogels.

  Culturing epithelial organoids from Adult Stem Cells (ASCs) requires interaction of their β1-integrins with extracellular matrix (ECM) components such as laminin or collagen. Matrigel and BME® (extracts from Engelbreth-Holm-Swarm tumor cells grown in the mouse abdomen) are a popular source of ECM proteins. Yet, these preparations are costly and subject to batch-to-batch variation due to animal-derived contaminations. Here, we describe a single chain version (scFv) of antibody TS2/16, allosterically activating integrin β1 function in organoids. Addition of 5 nM of monomeric scFv to organoid medium results in up to 5-fold higher yields of organoids in Matrigel/BME®. In addition, scTS2/16 generates 6-7-fold higher yields of intestinal organoids in collagen-I hydrogel, when grown both in 3D and in 2D. Collagen is well-defined, available at clinical grade, and in combination with scTS2/16, will enable the clinical use of gastrointestinal organoids.

  Study EGAS50000001113

• High-grade B-cell lymphoma, not otherwise specified: an LLMPP study

  Molecular characterization of high-grade B-cell lymphoma, not otherwise specified (HGBCL-NOS), is hindered by its rarity, evolving definition, and poor diagnostic reproducibility. To address this challenge, we analyzed 92 HGBCL-NOS tumors collected across Lymphoma/Leukemia Molecular Profiling Project sites. These tumors were profiled using whole-genome sequencing (WGS) or whole-exome sequencing (WES) to identify somatic mutations, WGS or low-pass WGS to detect copy number alterations, targeted capture sequencing to assess MYC and BCL2 structural variants, and RNA sequencing. The genetic features of HGBCL-NOS were compared to those of diffuse large B-cell lymphoma (DLBCL-NOS) and EBV-negative adult Burkitt lymphoma (BL). DLBCL-NOS tumors underwent targeted capture sequencing using a panel of 125 genes recurrently mutated in aggressive B-cell lymphomas. BL biopsies were drawn from the Burkitt Lymphoma Genome Sequencing Project and had available WGS (dbGaP Study Accession: phs000527.v18.p6).

  Study EGAS50000000932

• The evolution of hematopoietic cells under cancer therapy

  Chemotherapies may increase mutagenesis of healthy cells and change the selective pressures in tissues thus influencing their evolution. However, their contributions to the mutation burden and clonal expansions of healthy somatic tissues are not clear. Here, exploiting the mutational footprint of some chemotherapies, we explore their influence on the evolution of hematopoietic cells. Cells of Acute Myeloid Leukemia (AML) secondary to treatment with platinum-based drugs showed the mutational footprint of these drugs, indicating that non-malignant blood cells received chemotherapy mutations. No trace of 5-fluorouracil (5FU) mutational signature was found in AML secondary to exposure to 5FU, suggesting that cells establishing the AML were quiescent during treatment. Using the platinum-based mutational signature as a barcode, we determined that secondary AMLs began their clonal expansion after the start of the cytotoxic treatment. Its absence in clonal hematopoiesis cases is consistent with a clonal expansion that predates the exposure to the cytotoxic agent.

  Study EGAS00001005234

• Exome & MiSeq sequencing of individuals with Huntington's disease

  The age at onset of motor symptoms in Huntington's disease (HD) is driven by HTT CAG repeat length but modified by other genes. In this study, we used exome sequencing of 683 patients with HD with extremes of onset or phenotype relative to CAG length to identify rare variants associated with clinical effect. We discovered damaging coding variants in candidate modifier genes identified in previous genome-wide association studies associated with altered HD onset or severity. Variants in FAN1 clustered in its DNA-binding and nuclease domains and were associated predominantly with earlier-onset HD. Nuclease activities of purified variants in vitro correlated with residual age at motor onset of HD. Mutating endogenous FAN1 to a nuclease-inactive form in an induced pluripotent stem cell model of HD led to rates of CAG expansion similar to those observed with complete FAN1 knockout. Together, these data implicate FAN1 nuclease activity in slowing somatic repeat expansion and hence onset of HD.

  Study EGAS00001006383

• Longitudinal sequencing of a recurrent paediatric high grade neuroepithelial tumour

  We have studied a unique case of astroblastoma arising in a 6 year-old girl, with multiple recurrences over a period of 10 years, with the pathognomonic MN1:BEND2 fusion 11 surgical samples from either fresh frozen of paraffin embedded material and 1 blood sample were subjected to Illumina short read whole exome sequencing using Agilent SureSelect whole exome v4. Data is provided as 15 BAM files aligned to hg19 with bwa.

  Dataset EGAD00001004118

• Congenital Heart Disease in UK Families

  This project aims to identify highly penetrant coding variants increasing the risk of Congenital Heart Disease (CHD) performing whole exome sequencing on DNA samples from 23 affected individuals, selected from 10 families with presumed Autosomal Recessive Inheritance. This is a collaboration with Prof. Eamonn Maher and Dr. Chirag Patel from the Department of Medical and Molecular Genetics, University of Birmingham plans to sequence 23 indexed Agilent whole exome pulldown libraries on 75Bp PE HiSeq (Illumina)

  Dataset EGAD00001000343

• Exome sequence of probands in Barrett's oesophagus families

  Barrett?s oesophagus is common in the UK affecting 2 % of the population. Family history has been recorded among the 4000 Barrett's cases collected so far and have 241 families. Among them we have assessed 6 multiplex families with proven Barrett?s and defined as having 1 pro band and at least 3 affected first degree members. We propose to exome sequence the probands of these six families to assess the presence of pathogenic rare coding variants.

  Dataset EGAD00001002181

• Breast Cancer - immune clusters - RNA-seq

  In this study we use expression data from breast cancer tumors to define immune clusters in breast cancer. Immune clusters have gradual levels of immune infiltration. In the intermediate immune infiltration cluster, we found a worse prognosis which is independent of known clinicopathological features. We also found the immune clusters associated with treatment response. Further using gene expression data and deconvolution algorithms to dissect the immune contexture of the clusters.

  Dataset EGAD00001004985

• Biallelic variants in the non-protein coding minor spliceosome components RNU6ATAC and RNU6ATAC cause syndromic monogenic autoimmune diabetes

  Non-protein coding genes are emerging as critical contributors to the aetiology of rare diseases, providing key insights into human biology and uncovering novel disease mechanisms. We identified 7 individuals from 4 families with early-onset diabetes (diagnosed <5 years) and immune dysregulatory features caused by biallelic variants in RNU6ATAC. RNU6ATAC encodes a small nuclear RNA (snRNA) acting as a catalytic component of the minor spliceosome, a protein-RNA complex mediating splicing of ~700 genes containing U12/minor-type introns. Variant screening of the other 64 minor spliceosome genes in 276 infants with diabetes identified 12 unrelated individuals with biallelic disease-causing variants in RNU4ATAC. Biallelic pathogenic RNU4ATAC variants are known to cause a variable spectrum of clinical features, which until now did not include diabetes. Clinically, 12/19 RNU6ATAC/RNU4ATAC patients had additional immune dysregulatory features, and 50% of patients tested were islet-autoantibody positive, strongly supporting an autoimmune aetiology for their diabetes. RNA-seq in 3 individuals with biallelic RNU6ATAC variants showed a pattern of intron retention in U12 intron-containing genes similar to that seen in RNU4ATAC-individuals (n=3), supporting a shared disease mechanism. Analysis of patients’ transcriptomic, methylation and immune data revealed impaired B cell development and maturation. We conclude that biallelic RNU6ATAC variants cause a novel syndrome of early-onset autoimmune diabetes and immune dysregulation. We further show that infancy-onset diabetes is a previously unrecognised feature of RNU4ATACopathy. Our work highlights the important role of two snRNAs critical to minor spliceosome function in immune system regulation, providing novel insights into the pathogenesis of autoimmune diabetes.

  Study EGAS50000001565

• Single-cell decoding of drug induced transcriptomic reprogramming in triple negative breast cancers

  Background The encoding of cell intrinsic drug resistance states in breast cancer reflects the contributions of genomic and non-genomic variations and requires accurate estimation of clonal fitness from co-measurement of transcriptomic and genomic data. Somatic copy number (CN) variation is the dominant mutational mechanism leading to transcriptional variation and notably contributes to platinum chemotherapy resistance cell states. Here, we deploy time series measurements of triple negative breast cancer (TNBC) single-cell transcriptomes, along with co-measured single-cell CN fitness, identifying genomic and transcriptomic mechanisms in drug associated transcriptional cell states. Results We present scRNA-seq data (53,641 filtered cells) from serial passaging TNBC patient-derived xenograft (PDX) experiments spanning 2.5 years, matched with genomic single-cell CN data from the same samples. Our findings reveal distinct clonal responses within TNBC tumors exposed to platinum. Clones with high drug fitness undergo clonal sweeps and show subtle transcriptional reversion, while those with weak fitness exhibit dynamic transcription upon drug withdrawal. Pathway analysis highlights convergence on epithelial-mesenchymal transition and cytokine signaling, associated with resistance. Furthermore, pseudotime analysis demonstrates hysteresis in transcriptional reversion, indicating generation of new intermediate transcriptional states upon platinum exposure. Conclusions Within a polyclonal tumor, clones with strong genotype-associated fitness under platinum remained fixed, minimizing transcriptional reversion upon drug withdrawal. Conversely, clones with weaker fitness display non-genomic transcriptional plasticity. This suggests CN-associated and CN-independent transcriptional states could both contribute to platinum resistance. The dominance of genomic or non-genomic mechanisms within polyclonal tumors has implications for drug sensitivity, restoration and re-treatment strategies.

  Study EGAS00001007242

• Single Cell Analysis of Pulmonary Fibrosis

  Pulmonary fibrosis is a heterogenous syndrome in which fibrotic scar replaces normal lung tissue. We performed massively parallel single-cell RNA-Seq on lung tissue from eight lung transplant donors and eight patients with pulmonary fibrosis. Combined with in situ RNA hybridization, with amplification, these data provide a molecular atlas of disease pathobiology. We identified a distinct, novel population of profibrotic alveolar macrophages exclusively in patients with fibrosis. Within epithelial cells, the expression of genes involved in Wnt secretion and response was restricted to non-overlapping cells. We identified rare cell populations including airway stem cells and senescent cells emerging during pulmonary fibrosis. Analysis of a cryobiopsy specimen from a patient with early disease supports the clinical application of single-cell RNA-Seq to develop personalized approaches to therapy.

  Study phs001750

• RNA-Seq from PMM2-CDG Patients and Healthy Controls

  Besides the predominant neurological involvement of PMM2-CDG patients, around 20% of patient mortality has been linked to severe infections. However, the immunological dysfunction in PMM2-CDG is not well understood. In this study, we aimed to address this gap and study the molecular mechanisms affected behind immunological issues in PMM2-CDG. Primary skin fibroblasts from three PMM2-CDG patients and three healthy controls were stimulated or not with TNF-alpha and their gene expression was assessed by RNA sequencing. The response to TNF-alpha was characterized based on the differential expressed genes and functional enrichment and and compared between PMM2-CDG and healthy individuais. Gene expression alterations and functional enrichment were further validated by several experimental assays by ELISA, Flow Cytometry and Western Blotting.

  Study phs003313

• NHLBI GO-ESP: Family Studies (Familial Interstitial Pneumonia)

  The NHLBI "Grand Opportunity" Exome Sequencing Project (GO-ESP), a signature project of the NHLBI Recovery Act investment, was designed to identify genetic variants in coding regions (exons) of the human genome (the "exome") that are associated with heart, lung and blood diseases. These and related diseases that are of high impact to public health and individuals from diverse racial and ethnic groups will be studied. These data may help researchers understand the causes of disease, contributing to better ways to prevent, diagnose, and treat diseases, as well as determine whether to tailor prevention and treatments to specific populations. This could lead to more effective treatments and reduce the likelihood of side effects. GO-ESP is comprised of five collaborative components: 3 cohort consortia - HeartGO, LungGO, and WHISP - and 2 sequencing centers - BroadGO and SeattleGO. The Familial Interstitial Pneumonia (FIP) project seeks to identify genetic variants in coding regions of the human genome that are linked to FIP by examining the coding regions among relatives with FIP. These data will be used in conjunction with our other genetic studies to help us better understand how and why some individuals develop pulmonary fibrosis.

  Study phs000582

• Addiction of Primary Cutaneous Gamma-Delta T-cell Lymphomas to JAK-STAT Signaling

  Primary cutaneous &#947;&#948; T-cell lymphoma (PCGDTL) is a mature T-cell lymphoma (TCL) of the skin with a median survival of 31 months and no effective therapies. PCGDTLs frequently possess mutations in the JAK/STAT pathway, including in JAK1, JAK3, STAT3, STAT5B, and SOCS1. We hypothesized that single-agent JAK inhibition may be effective in PCGDTLs, particularly those with targetable JAK/STAT pathway mutations. Herein, we demonstrate the near-complete response of two PCGDTL cases to single-agent JAK inhibitors, ruxolitinib or cerdulatinib. However, both patients eventually relapsed with acquired mutations in JAK1, JAK3, or STAT5B.

  Study phs003837

• Gut metagenome/FINRISK 2002 (Salosensaari et al. Nature Comms 2021)

  The main goal of the project is the study the associations between the gut metagenome and human health. The dataset contains data for n=7211 FINRISK 2002 participants who underwent fecal sampling. Demultiplexed shallow shotgun metagenomic sequences were quality filtered and adapter trimmed using Atropos (Didion et al., 2017), and human filtered using Bowtie2 (Langmead and Salzberg, 2012).

  Study EGAS00001005020

• Singel-cell RNA sequencing and CUT&RUN sequencing of human RUNX2-deficient osteoblasts

  Runx2 is a master regulator of bone formation, and its dysfunction causes cleidocranial dysplasia (CCD) in humans. When iPS cells were generated from patients with CCD and Runx2-deficient iPS cells were generated using gene-editing techniques, abnormal laminopathy-like nuclei were observed. Runx2-deficient cells showed reduced Lamin A/C expression, but not protein levels. However, in Runx2-deficient cells, both the gene expression and protein levels of Nesprin-1 were reduced, perinuclear actin fibers were sparser, and nuclear stiffness was reduced. Forced expression of Lamin A/C increased nuclear stiffness but did not improve nuclear morphology. In contrast, the induction of Nesprin-1 expression alone normalized nuclear stiffness and restored nuclear morphology and perinuclear actin distribution. In Runx2-null cells, mechanical stress-induced phosphorylation of emerin was not observed. In contrast, forced expression of nesprin-1 in Runx2-null cells resulted in phosphorylation of emerin, indicating the restoration of intracellular tension. These observations were confirmed by atomic force microscopy. Therefore, the intracellular tension was inferred to pull the nuclear membrane into its normal shape. CUT&RUN assay and single RNA-seq analysis showed that an aberrant nuclear membrane caused loss of nuclear lamina gene regulation machinery, making the progression of normal osteogenic differentiation impossible; however, supplementation with Nesprin-1 restored gene regulation mechanisms and promoted pre-osteoblast formation with normal nuclear morphology. Nesprin-1 expression induced by Runx2 is essential for epigenetic regulation of the nuclear lamina. We propose CCD as a new type of laminopathy involving defective expression of Nesprin-1 regulated by Runx2.

  Study JGAS000663

• Epigenomic dataset of Human Hepatocellular Carcinoma for EpiHK

  This dataset is generated for EpiHK. It contains Histone PTM ChIP-seq, WGBS, RNA-seq of 7 Human Hepatocellular Carcinoma and 7 tumor adjacent normal tissue sample.

  Dataset EGAD50000000058

• Waldenström Macroglobulinemia Single-Cell Data Access Committee

  This Data Access Committee (DAC) is responsible for reviewing and approving access requests for controlled-access human single-cell sequencing data, including single-cell RNA sequencing and immune receptor profiling, generated from patients with Waldenström macroglobulinemia. The DAC ensures that all data access requests comply with the informed consent provided by study participants and are consistent with applicable ethical and regulatory requirements.

  Dac EGAC50000000863

• RNA-seq data of 370 high grade ovarian tumors from the ICON7 trial

  Collection of RNA-seq, Illumina, paired-end fastq files for 370 archival tissues from a subset of patients with high grade serous ovarian carcinoma enrolled in the phase 3 ICON7 trial. Clinical data and digital pathology information for CD8 is also available.

  Dataset EGAD00001004988

• Identification of a Fumarate-Hydratase Deficient-like RCC Subtype with Convergent Pathway Alterations

  The development of molecularly targeted therapies builds upon the identification of tumor clades with shared molecular abnormalities. Hereditary leiomyomatosis and renal cell carcinoma (HLRCC) is a familial syndrome resulting from germline mutation of the two-hit tumor suppressor gene, Fumarate Hydratase (FH). HLRCC renal tumors present often in young adults, exhibit unique histological features and are particularly aggressive. HLRCC is uncommon and poorly understood, and whether there are sporadic renal tumors with similar characteristics, is unclear. Notably, FH can also be inactivated somatically in RCC, and should be included among FH-deficient (FHD) kidney tumors. We identified a tumor clade without FH mutations but with similar morphological and molecular characteristics as well as aggressive clinical behavior, which we name FHDL (FHD-like). We show that FHD/FHDL tumors represent a unique subtype of CIMP (CpG Island Methylator Phenotype) with the highest levels of overall genome methylation and CDKN2A silencing. FHD/FHDL tumors are characterized by convergent activation of the Hippo pathway as determined by frequent and mutually exclusive mutations in NF2 and PTPN14. AKR1B10, an NRF2 target, was upregulated in FHD/FHDL tumors as well as GATA3, which suggests a shared origin in the renal medulla and is consistent with topological studies. There is loss of 5-hydroxymethylcytosine in both FHD and FHDL tumors. These data define a group of particularly aggressive renal cancers with shared molecular features and potential targets for therapeutic intervention.

  Study EGAS00001002646

• Genomic Sequencing of Ewing Sarcoma

  Pediatric Ewing sarcoma is a pediatric cancer that primarily arises from the bone. It is characterized by chimeric fusions of the EWS gene and an ETS family transcription factor. In this study, we performed massively parallel sequencing of a larger collection of Ewing sarcoma tumors to define the genomic landscape of this disease. We found that these tumors are among of the most genetically normal cancers currently characterized. There was also a marked absence of recurrent mutations in immediately targetable signaling transduction pathway genes. In this study we answer outstanding questions about ETS transcription factor expression, effects of treatment on mutational burden in Ewing sarcoma tumors, and describe patterns of tumor evolution. We also found that loss-of-function mutations in STAG2 were present in approximately 15% of Ewing sarcoma tumors and loss of STAG2 expression was associated with disease metastasis in this patient cohort.

  Study phs000804

• COPD and neutrophils

  Chronic obstructive pulmonary disease (COPD) is a major respiratory disease characterized by small airway inflammation, emphysema and severe breathing difficulties. Low-grade systemic inflammation is an established hallmark of severe disease, however, the molecular changes in peripheral immune cells remain far from understood. We combined multi-color flow cytometry with single-cell RNA sequencing and showed that blood neutrophil numbers are significantly increased in COPD and they are a heterogeneous population. A transcriptomic state that expressed interferon response genes correlated with alveolar damage and acute exacerbations. Furthermore, bronchoalveolar neutrophils expressed gene signatures corresponding to certain blood neutrophil states. Last, our data in a murine model of cigarette smoke exposure demonstrated that bone marrow neutrophil progenitors are expanded in smoke-treated animals and display signs of immune activation. Our study provides evidence that COPD systemic inflammation may derive from an activated haematopoietic precursor compartment.

  Study EGAS00001006281

• COPD and neutrophils sc

  Chronic obstructive pulmonary disease (COPD) is a major respiratory disease characterized by small airway inflammation, emphysema and severe breathing difficulties. Low-grade systemic inflammation is an established hallmark of severe disease, however, the molecular changes in peripheral immune cells remain far from understood. We combined multi-color flow cytometry with single-cell RNA sequencing and showed that blood neutrophil numbers are significantly increased in COPD and they are a heterogeneous population. A transcriptomic state that expressed interferon response genes correlated with alveolar damage and acute exacerbations. Furthermore, bronchoalveolar neutrophils expressed gene signatures corresponding to certain blood neutrophil states. Last, our data in a murine model of cigarette smoke exposure demonstrated that bone marrow neutrophil progenitors are expanded in smoke-treated animals and display signs of immune activation. Our study provides evidence that COPD systemic inflammation may derive from an activated haematopoietic precursor compartment.

  Study EGAS00001006322

• COPD and neutrophils sc rhapsody

  Chronic obstructive pulmonary disease (COPD) is a major respiratory disease characterized by small airway inflammation, emphysema and severe breathing difficulties. Low-grade systemic inflammation is an established hallmark of severe disease, however, the molecular changes in peripheral immune cells remain far from understood. We combined multi-color flow cytometry with single-cell RNA sequencing and showed that blood neutrophil numbers are significantly increased in COPD and they are a heterogeneous population. A transcriptomic state that expressed interferon response genes correlated with alveolar damage and acute exacerbations. Furthermore, bronchoalveolar neutrophils expressed gene signatures corresponding to certain blood neutrophil states. Last, our data in a murine model of cigarette smoke exposure demonstrated that bone marrow neutrophil progenitors are expanded in smoke-treated animals and display signs of immune activation. Our study provides evidence that COPD systemic inflammation may derive from an activated haematopoietic precursor compartment.

  Study EGAS00001006323

• Short and long-read sequencing of Brugada syndrome samples

  Genome-wide association studies (GWAS) are instrumental in identifying loci with an impact on human traits and disease. Typically, however, most GWAS information is considered redundant as it is based on neighboring single-nucleotide variants (SNVs) in strong linkage disequilibrium (LD). In this context, besides the most significant hit (lead SNV) in every trait- or disease-associated locus, the rest of GWAS hits are often marginally reported, examined, or exploited. To interrogate the value of integrating the information provided by the full set of GWAS hits and fine-mapping haplotypes containing these SNVs, here we focused on a locus repeatedly associated with traits of the cardiac electrical conduction system and arrhythmia (SCN5A-SCN10A). We found that the same SNV can exhibit differing associations depending on haplotype. Thus, these analyses provide corroborative evidence that assuming redundancy among neighboring GWAS hits has the risk of missing critical disease-risk associations.

  Study EGAS00001004927

• Deciphering the genomic, epigenomic and transcriptomic landscapes of pre-invasive lung cancer lesions to determine prognosis

  Background: Lung carcinoma-in-situ (CIS) lesions are the pre-invasive precursor to lung squamous cell carcinoma. However, only half progress to invasive cancer in three years, while a third spontaneously regress. Whether modern molecular profiling techniques can identify those pre-invasive lesions that will subsequently progress and distinguish them from those that will regress is unknown. Methods: Progressive and regressive CIS lesions were laser-captured and their genome, epigenome and transcriptome interrogated. We analysed 83 progressive lesions, 41 regressive and 33 normal epithelial control samples. DNA methylation and gene expression profiles were further validated using publicly available lung cancer data. Results: Somatic mutation burden was higher in progressive lesions than regressive CIS lesions, across base substitutions, rearrangements, and copy number changes. Driver mutations were present in both progressive and regressive CIS lesions, but were more numerous in progressive cases. Progressive and regressive CIS lesions had distinct epigenomic and transcriptional profiles, with a strong chromosomal instability signature. Gene expression, methylation and copy number profiles can all predict accurately which CIS lesions will progress to lung cancer. Conclusion: Pre-invasive CIS lesions that will subsequently progress to invasive lung cancer can be distinguished from those that will regress using molecular profiling. Progression is associated with a strong chromosomal instability signature. These findings inform the development of novel therapeutic targets.

  Dataset EGAD00001003883

• Systemic Lupus Erythematosus Serum Stimulation of Human Intestinal Organoids Induces Barrier Leakiness and Changes in Goblet Cell Differentiation

  Human intestinal epithelial cells are the interface between potentially harmful luminal content and basally residing immune cells. Their role is not only nutrient absorption but also the formation of a tight monolayer that constantly secretes mucus creating a multi-layered protective barrier. Alterations in this barrier can lead to increased gut permeability which is frequently seen in individuals with chronic extraintestinal autoimmune diseases, such as Systemic Lupus Erythematosus (SLE). Despite recent advances in identifying alterations in gut microbiota composition in SLE patients, not much attention has been given to the epithelial barrier itself. To date, it remains largely unexplored which role and function intestinal epithelial cells have in SLE pathology. Here, we present a unique near-physiologic in vitro model specifically designed to examine the effects of SLE on the epithelial cells. We utilize human colon organoids that are stimulated with serum obtained from SLE patients. Combining bulk and single-cell RNA transcriptomic analysis with functional assays revealed that SLE serum stimulation induced a unique expression profile marked by a reduction of goblet cell marker expression and mucus composition. Additionally, organoids exhibited imbalanced cellulat composition along with enhanced paracellular permeability,mitochondrial function, and a type I interferon gene signature. Similarly, transcriptomic analysis of SLE human colon biopsies revealed a downregulation of epithelial secretory markers. Our work uncovers a crucial connection between SLE and intestinal homeostasis that might be promoted in vivo through the blood, offering insights into the causal connection of barrier dysfunction and autoimmune diseases.

  Study EGAS50000000012

• ZNF703 is a common Luminal B breast cancer oncogene that differentially regulates luminal and basal progenitors in human mammary epithelium.

  The telomeric amplicon at 8p12 is common in oestrogen receptor-positive (ER+) breast cancers. Array-CGH and expression analyses of 1172 primary breast tumours revealed that ZNF703 was the single gene within the minimal amplicon and was amplified predominantly in the Luminal B subtype. Amplification was shown to correlate with increased gene and protein expression and was associated with a distinct expression signature and poor clinical outcome. ZNF703 transformed NIH 3T3 fibroblasts, behaving as a classical oncogene, and regulated proliferation in human luminal breast cancer cell lines and immortalized human mammary epithelial cells. Manipulation of ZNF703 expression in the luminal MCF7 cell line modified the effects of TGFβ on proliferation. Overexpression of ZNF703 in normal human breast epithelial cells enhanced the frequency of in vitro colony-forming cells from luminal progenitors. Taken together, these data strongly point to ZNF703 as a novel oncogene in Luminal B breast cancer.

  Study EGAS00000000082

• The T cell receptor repertoire of tumor infiltrating T cells is predictive and prognostic for cancer survival

  Transcriptomic sequencing on pre-immunotherapy melanoma patients.

  Dataset EGAD00001007710

• Mutation-specific non-canonical pathway of PTEN as a distinct therapeutic target for glioblastoma

  PTEN is one of most frequently altered tumor suppressor genes in malignant tumors. The dominant negative effect of PTEN alteration suggests that aberrant function of PTEN mutation might be more disastrous than deletion, the most frequent genomic event in glioblastoma (GBM). This study aimed to understand the functional properties of various PTEN missense mutations and to investigate their clinical relevance. The genomic landscape of PTEN alteration was analyzed using the Samsung Medical Center GBM cohort and validated via The Cancer Genome Atlas dataset. Several hot-spot mutations were identified, and their subcellular distributions and phenotypes were evaluated. We established a library of cancer cell lines that over-express these mutant proteins using the U87MG and patient-derived cell models lacking functional PTEN. PTEN mutations were categorized into two major subsets: missense mutations in the phosphatase domain and truncal mutations in the C2 domain. We determined the subcellular compartmentalization of four mutant proteins (H93Y, C124S, R130Q, and R173C) from the former group and found that they had distinct localizations; those associated with invasive phenotypes (‘edge mutations’) localized to the cell periphery, while the R173C mutant localized to the nucleus. Invasive phenotypes derived from edge substitutions were unaffected by an anti-PI3K/Akt agent but were disrupted by microtubule inhibitors. PTEN mutations exhibit distinct functional properties with regard to their subcellular localization. Further, some missense mutations (‘edge mutations’) in the phosphatase domain caused enhanced invasiveness associated with dysfunctional cytoskeletal assembly, thus suggesting it to be a potent therapeutic target.

  Study EGAS00001004753

• Histone chaperone CHAF1A promotes proliferation and tumorigenicity in gastric cancer and impacts prognosis via context-depedent regulation of gene expression

  The histone chaperone CHAF1A is associated with some tumors, but its mechanisms in tumor biology remain elusive. Gastric cancer (GC) has significant heterogeneity among patients, and novel prognostic markers and therapeutic targets may improve its outcomes. The role of CHAF1A in GC is unknown. In this study, we demonstrated that CHAF1A was overexpressed in GC tissues accompanied by low expression of wild-type P53 and high expression of the proliferation marker MKI67. In vitro, CHAF1A knockdown inhibited cell proliferation, induced cell cycle arrest and promoted apoptosis, while CHAF1A overexpression had contrary effects. In vivo, CHAF1A knockdown inhibited tumorigenicity of GC cells. A microarray assay with CHAF1A inhibition and a PathScan signaling antibody array with CHAF1A overexpression showed that CHAF1A inhibited the P53 pathway, activated stress response and induced glycolytic metabolism. In 665 patients, the expression level of CHAF1A protein was an independent predictor for overall survival and disease-free survival in non-cardia GC and also had survival associations in patients with small or perineural invasion-negative tumors. Tumor mRNA analyses based on next-generation sequencing in patients indicated that CHAF1A promoted the Warburg effect by depressing oxidative phosphorylation and increasing glycolysis. Furthermore, the heterogeneous clinical significance of CHAF1A among patient subgroups was associated with its differential regulation of gene expression involved with glycolysis and cell proliferation and survival, indicating that the role of CHAF1A is depended on patient characteristics. These results reveal critical roles and clinical values for CHAF1A in GC. CHAF1A may have context-dependent effects in GC, which increases understandings for GC heterogeneity.

  Study EGAS00001003064

• A new beta-globin mutation responsible of a beta-thalassemia (HbVar database ID 2928) was observed in 8 unrelated French families. The mutation carriers originated from Nord-Pas-de-Calais, a Northern French region where the chief town is Lille.5 unrelated mutation carriers were genotyped for a set of 12 microsatellites from chromosome 11, around the beta-globin gene. Among the 5 mutation carriers, 4 were genotyped for 97 European Ancestry Informative SNPs (EAIMs). 32 controls from Nord-Pas-de-Calais were genotyped for the microsatellites and SNPs.

  Dac EGAC00001000245

• DAC for "Longitudinal copy number variation analysis from plasma DNA of head and neck cancer patients under re-radiotherapy"

  This is the DAC for "Longitudinal copy number variation analysis from plasma DNA of head and neck cancer patients under re-radiotherapy" with Florian Janke f.janke@dkfz-heidelberg.de German Cancer Research Center, Division of Cancer Genome Research Holger Sültmann h.sueltmann@dkfz-heidelberg.de German Cancer Research Center, Division of Cancer Genome Research Magdalena Görtz magdalena.goertz@dkfz-heidelberg.de German Cancer Research Center, Multiparametric Methods for Early Detection of Prostate Cancer

  Dac EGAC50000000114

• Isotype-resolved sequencing of B-cell receptor in sorted memory populations (2017-09-13)

  Optimisation of ex vivo Memory B cell Expansion/Differentiation for Interrogation of Rare Peripheral Memory B Cell Subset Responses 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/ This dataset contains all the data available for this study on 2017-09-13.

  Dataset EGAD00001003747

• APOLLO1: Proteogenomic Analysis of Lung Adenocarcinoma

  APOLLO is a proteogenomic study seeking to describe the major genome, transcriptome, proteome and phosphoproteome alterations, subtypes, and molecular predictors of patient outcomes. This study includes 87 lung adenocarcinomas and matched normal tissues from the Lung Cancer Biospecimen Resource Network (https://lungbio.sites.virginia.edu/). Tumor tissues were profiled by whole genome sequencing, transcriptome sequencing, MS-based proteomics and phosphoproteomics, and reverse phase protein arrays. Matched normal tissues were profiled by whole genome sequencing. Clinical and sample data include survival times, patient features, and tumor characteristics.

  Study phs003011

• APOLLO-OV: Applied Proteogenomics of High Grade Serous Ovarian Carcinoma

  APOLLO is a proteogenomic study seeking to describe the major genome, transcriptome, proteome and phosphoproteome alterations, subtypes, and molecular predictors of patient outcomes. This study includes 70 high grade serous ovarian carcinoma tissues from the Gynecologic Cancer Center of Excellence (https://medschool.usuhs.edu/gso/research/gyn-cancer-center-of-excellence). Bulk and laser microdissection enriched tumor tissues were profiled by whole genome sequencing, transcriptome sequencing, MS-based proteomics and reverse phase protein arrays. Clinical and sample data include survival times, patient features, and tumor characteristics.

  Study phs003488

• The Genetic Landscape of Familial Pulmonary Fibrosis

  This dataset was collected from a study that was designed to identify disease-causing rare genetic variants in individuals with Familial Interstitial Pneumonia (FIP). Subjects were identified from our ongoing FIP Registry (IRB #020343), where FIP is defined as idiopathic interstitial lung disease (ILD) in two or more family members with at least one affected individual diagnosed with idiopathic pulmonary fibrosis (IPF). Whole exome sequencing was performed on ~600 affected members from 525 kindreds using genomic DNA isolated from peripheral blood.

  Study phs003750

• Identification of G-Quadruplex Clusters by High-Throughput Sequencing of Whole-Genome Amplified Products with a G-Quadruplex Ligand

  G-quadruplex (G4) is a non-canonical DNA structure that has been found in the genome. To identify clusters of G4-forming sequences in the genome, we performed whole genome amplification (WGA) in the presence or absence of a G4 ligand that inhibits DNA polymerase activity on the G4 forming regions, followed by high-throughput sequencing of the WGA products. As the results, 12254 G4 cultures were identified on HeLa genomic DNA.

  Study phs001450

• Genomic analysis of HGSOC using long read sequencing

  High-grade serous ovarian cancer (HGSOC) is characterized by widespread genomic instability, but genomic and epigenomic alterations within repetitive regions remain poorly understood. This study aims to investigate genomic and epigenomic variations in HGSOC using Oxford Nanopore long-read sequencing technology. High-molecular-weight DNA was extracted from cryopreserved, pre-treatment tumor samples and matched blood specimens. The objectives include developing a robust long-read sequencing analysis pipeline, identifying novel genomic and epigenomic variations, and exploring potential applications in future clinical and basic research.

  Study EGAS50000001036

• Genetic Legacy of Punan Hunter-Gatherer Groups in Indonesian Borneo

  Punan Batu (the “Cave Punan”), the last living nomadic hunter-gatherer (HG) group who still literally live under karst rock shelters in Borneo, is the least-known hunter-gatherer society in Asia. To provide insights on the origin and adaptation of the Cave Punan, here we present the autosomal genome-wide SNPs study of the Cave Punan, including other Punan groups who speak different language from the Cave Punan, which are transitioning into a more sedentary lifestyle.

  Study EGAS00001004471

• Small cell carcinoma of the ovary, hypercalcemic type, displays frequent inactivating germline and somatic mutations in SMARCA4

  Small cell carcinoma of the ovary of hypercalcemic type (SCCOHT) is an extremely rare, aggressive cancer affecting children and young women. We identified germline and somatic inactivating mutations in the SWI/SNF chromatin-remodeling gene SMARCA4 in 75% (9/12) of SCCOHT patients in addition to SMARCA4 protein loss in 82% (14/17) of SCCOHT tumors, but in only 0.4% (2/485) of other primary ovarian tumors. These data implicate SMARCA4 in SCCOHT oncogenesis.

  Study EGAS00001000714

• Novel PARN mutations in Hoyeraal-HReidarsson syndrome patients.

  The deposited data correspond to the sequences of PARN gene obtained by whole exome sequencing in two patients carrying mutations in this gene as described in Benyelles et al. EMBO Mol Med 2019.. PARN is a poly(A)-specific ribonuclease that regulates the turnover of mRNAs and the maturation and stabilization of the hTR RNA component of telomerase. Data represent Sequences with PARN mutations that have been identified in two patients with Høyeraal-Hreidarsson (HH) syndrome, a rare telomere biology disorder.

  Study EGAS00001003623