14982 results for "cancer studies using rna-seq"

in 25.78 milliseconds.

• Center for Common Disease Genomics [CCDG] Neuropsychiatric: Autism Spectrum Disorder (ASD) – Whole Exomes

  The National Human Genome Research Institute (NHGRI) has funded a collaborative large-scale genome sequencing effort to comprehensively identify rare risk and protective variants contributing to multiple common disease phenotypes. Called the Centers for Common Disease Genomics (CCDG), this initiative will explore a range of diseases with the ultimate goal of 1) undertaking variant discovery for enough different examples of disease architectures and study designs to better understand the general principles of the genomic architecture underlying common, complex inherited diseases, 2) understanding how best to design rare variant studies for common disease, and 3) developing resources, informatics tools, and innovative approaches and technologies for multiple disease research communities and the wider biomedical research community. The initial focus of the CCDGs will be in cardiovascular disease (early-onset coronary artery disease, atrial fibrillation, hemorrhagic stroke), neuropsychiatric disease (epilepsy, autism), and autoimmune/inflammatory disease (type 1 diabetes, inflammatory bowel disease). The Broad Institute is one of four selected CCDG project centers. The goal of the Autism Spectrum Disorder (ASD) program is to work together to utilize dramatic new advances in DNA sequencing technology to reveal the genetic architecture of autism through comprehensive examination of the exotic sequence of all genes.

  Study phs002502

• Rare SNPs in receptor tyrosine kinases are negative outcome predictors in multiple myeloma

  Multiple myeloma (MM) is a plasma cell disorder that is characterized by a great genetic heterogeneity. Recent next generation sequencing studies revealed an accumulation of tumor-associated mutations in receptor tyrosine kinases (RTKs) which may also contribute to the activation of survival pathways in MM. To investigate the clinical role of RTK-mutations in MM, we deep-sequenced the coding DNA-sequence of EGFR, EPHA2, ERBB3, IGF1R, NTRK1 and NTRK2 which were previously found to be mutated in MM, in 75 uniformly treated MM patients of the "Deutsche Studiengruppe Multiples Myelom". Subsequently, we correlated the detected mutations with common cytogenetic alterations and clinical parameters. We identified 11 novel non-synonymous SNVs or rare patient-specific SNPs, not listed in the SNP databases 1000 genomes and dbSNP, in 10 primary MM cases. The mutations predominantly affected the tyrosine-kinase and ligand-binding domains and no correlation with cytogenetic parameters was found. Interestingly, however, patients with RTK-mutations, specifically those with rare patient-specific SNPs, showed a significant lower overall, event-free and progression-free survival. This indicates that RTK SNVs and rare patient-specific RTK SNPs are of prognostic relevance and suggests that MM patients with RTK-mutations could potentially profit from treatment with RTK-inhibitors.

  Study EGAS00001001665

• UK10K NEURO ABERDEEN

  In the UK10K project we propose a series of complementary genetic approaches to find new low frequency/rare variants contributing to disease phenotypes. These will be based on obtaining the genome wide sequence of 4000 samples from the TwinsUK and ALSPAC cohorts (at 6x sequence coverage), and the exome sequence (protein coding regions and related conserved sequence) of 6000 samples selected for extreme phenotypes. Our studies will focus primarily on cardiovascular-related quantitative traits, obesity and related metabolic traits, neurodevelopmental disorders and a limited number of extreme clinical phenotypes that will provide proof-of-concept for future familial trait sequencing. We will analyse directly quantitative traits in the cohorts and the selected traits in the extreme samples, and also use imputation down to 0.1% allele frequency to extend the analyses to further sample sets with genome wide genotype data. In each case we will investigate indels and larger structural variants as well as SNPs, and use statistical methods that combine rare variants in a locus or pathway as well as single-variant approaches. This sample set comprises cases of schizophrenia with additional cognitive measurements, collected in Aberdeen, Scotland.For further information on the Aberdeen cohort please contact David St Clair (d.stclair@abdn.ac.uk).

  Study EGAS00001000109

• Native American gene flow into Polynesia predating Easter Island settlement

  The possibility of voyaging contact between prehistoric Polynesian and Native American populations has long intrigued researchers. Proponents have pointed to the existence of New World crops, such as the sweet potato and bottle gourd, in the Polynesian archaeological record, but nowhere else outside the pre-Columbian Americas while critics have argued that these botanical dispersals need not have been human mediated. The Norwegian explorer Thor Heyerdahl controversially suggested that prehistoric South American populations had an important role in the settlement of east Polynesia and particularly of Easter Island (Rapa Nui). Several limited molecular genetic studies have reached opposing conclusions, and the possibility continues to be as hotly contested today as it was when first suggested. Here we analyse genome-wide variation in individuals from islands across Polynesia for signs of Native American admixture, analysing 807 individuals from 17 island populations and 15 Pacific coast Native American groups. We find conclusive evidence for prehistoric contact of Polynesian individuals with Native American individuals (around AD 1200) contemporaneous with the settlement of remote Oceania. Our analyses suggest strongly that a single contact event occurred in eastern Polynesia, before the settlement of Rapa Nui, between Polynesian individuals and a Native American group most closely related to the indigenous inhabitants of present-day Colombia.

  Study EGAS00001004209

• Exome_trios_in_patients_with_gastroschisis

  Gastroschisis (MIM 230750) is a herniation of the intestines through a defect of the abdominal wall lateral to the umbilicus (usually on the right side), and it is not covered by a membrane [Ledbetter, 2012]. Gastroschisis is a congenital anomaly with increasing incidence, easy prenatal diagnosis and extremely variable postnatal outcomes. On the basis of clinical manifestations, epidemiologic charateristics, and the presence and type of additional malformations, gastroschisis could be considered a heterogeneous condition with no gene/s discovered yet. This congenital anomaly affects approximately 1-3 infancts per 10,000 live births [Calzolari et al.1995;Parker et al.,2010] Current knowledge about causative mutations/variants. To date, no single gene has been linked to gastroschisis. Some publications have tried to link this malformation to variants in genes (such as AEBP1 (adipocyte enhancer binding protein) gene [Feldkamp et al,. 2012] or the VEGF-NOS3 pathway [Lammer et al., 2008]. Previously, a Scribble mutant mouse model (circletail) was reported to exhibit gastroschisis, however recent studies demonstrated that the Scribble knockout fetus exhibits exomphalos phenotype of gastroschisis [Carnagham et al., 2013]. 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 EGAS00001002664

• UK10K_RARE_NEUROMUSCULAR

  In the UK10K project we propose a series of complementary genetic approaches to find new low frequency/rare variants contributing to disease phenotypes. These will be based on obtaining the genome wide sequence of 4000 samples from the TwinsUK and ALSPAC cohorts (at 6x sequence coverage), and the exome sequence (protein coding regions and related conserved sequence) of 6000 samples selected for extreme phenotypes. Our studies will focus primarily on cardiovascular-related quantitative traits, obesity and related metabolic traits, neurodevelopmental disorders and a limited number of extreme clinical phenotypes that will provide proof-of-concept for future familial trait sequencing. We will analyse directly quantitative traits in the cohorts and the selected traits in the extreme samples, and also use imputation down to 0.1% allele frequency to extend the analyses to further sample sets with genome wide genotype data. In each case we will investigate indels and larger structural variants as well as SNPs, and use statistical methods that combine rare variants in a locus or pathway as well as single-variant approaches. The neuromuscular disorder samples are part of the “rare disease” group, and will undergo exome sequencing. For further information with regard to this cohort please contact Francesco Muntoni (f.muntoni@ucl.ac.uk).

  Study EGAS00001000101

• UK10K_RARE_FIND

  In the UK10K project we propose a series of complementary genetic approaches to find new low frequency/rare variants contributing to disease phenotypes. These will be based on obtaining the genome wide sequence of 4000 samples from the TwinsUK and ALSPAC cohorts (at 6x sequence coverage), and the exome sequence (protein coding regions and related conserved sequence) of 6000 samples selected for extreme phenotypes. Our studies will focus primarily on cardiovascular-related quantitative traits, obesity and related metabolic traits, neurodevelopmental disorders and a limited number of extreme clinical phenotypes that will provide proof-of-concept for future familial trait sequencing. We will analyse directly quantitative traits in the cohorts and the selected traits in the extreme samples, and also use imputation down to 0.1% allele frequency to extend the analyses to further sample sets with genome wide genotype data. In each case we will investigate indels and larger structural variants as well as SNPs, and use statistical methods that combine rare variants in a locus or pathway as well as single-variant approaches. The Raymond samples will be part of the “rare disease” group, and will undergo exome sequencing. For further information with regard to this cohort please contact Lucy Raymond (flr24@cam.ac.uk).

  Study EGAS00001000128

• UK10K_RARE_CILIOPATHIES

  In the UK10K project we propose a series of complementary genetic approaches to find new low frequency/rare variants contributing to disease phenotypes. These will be based on obtaining the genome wide sequence of 4000 samples from the TwinsUK and ALSPAC cohorts (at 6x sequence coverage), and the exome sequence (protein coding regions and related conserved sequence) of 6000 samples selected for extreme phenotypes. Our studies will focus primarily on cardiovascular-related quantitative traits, obesity and related metabolic traits, neurodevelopmental disorders and a limited number of extreme clinical phenotypes that will provide proof-of-concept for future familial trait sequencing. We will analyse directly quantitative traits in the cohorts and the selected traits in the extreme samples, and also use imputation down to 0.1% allele frequency to extend the analyses to further sample sets with genome wide genotype data. In each case we will investigate indels and larger structural variants as well as SNPs, and use statistical methods that combine rare variants in a locus or pathway as well as single-variant approaches. The Ciliopathies samples will be part of the rare disease group, and will undergo exome sequencing. For further information with regard to this cohort please contact Phil Beales (p.beales@ich.ucl.ac.uk).

  Study EGAS00001000126

• UK10K_RARE_SIR

  In the UK10K project we propose a series of complementary genetic approaches to find new low frequency/rare variants contributing to disease phenotypes. These will be based on obtaining the genome wide sequence of 4000 samples from the TwinsUK and ALSPAC cohorts (at 6x sequence coverage), and the exome sequence (protein coding regions and related conserved sequence) of 6000 samples selected for extreme phenotypes.Our studies will focus primarily on cardiovascular-related quantitative traits, obesity and related metabolic traits, neurodevelopmental disorders and a limited number of extreme clinical phenotypes that will provide proof-of-concept for future familial trait sequencing. We will analyse directly quantitative traits in the cohorts and the selected traits in the extreme samples, and also use imputation down to 0.1% allele frequency to extend the analyses to further sample sets with genome wide genotype data. In each case we will investigate indels and larger structural variants as well as SNPs, and use statistical methods that combine rare variants in a locus or pathway as well as single-variant approaches.The SIR (Severe Insulin Resistance) samples are part of the “rare disease” group, and will undergo exome sequencing. For further information with regard to this cohort please contact Robert Semple (rks16@cam.ac.uk).

  Study EGAS00001000130

• UK10K RARE CHD

  In the UK10K project we propose a series of complementary genetic approaches to find new low frequency/rare variants contributing to disease phenotypes. These will be based on obtaining the genome wide sequence of 4000 samples from the TwinsUK and ALSPAC cohorts (at 6x sequence coverage), and the exome sequence (protein coding regions and related conserved sequence) of 6000 samples selected for extreme phenotypes. Our studies will focus primarily on cardiovascular-related quantitative traits, obesity and related metabolic traits, neurodevelopmental disorders and a limited number of extreme clinical phenotypes that will provide proof-of-concept for future familial trait sequencing. We will analyse directly quantitative traits in the cohorts and the selected traits in the extreme samples, and also use imputation down to 0.1% allele frequency to extend the analyses to further sample sets with genome wide genotype data. In each case we will investigate indels and larger structural variants as well as SNPs, and use statistical methods that combine rare variants in a locus or pathway as well as single-variant approaches. The CHD (congenital heart disease) samples will be part of the “rare disease” group, and will undergo exome sequencing.For further information with regard to this cohort please contact Shoumo Bhattacharya (shoumo@me.com).

  Study EGAS00001000125

• UK10K OBESITY TWINSUK

  In the UK10K project we propose a series of complementary genetic approaches to find new low frequency/rare variants contributing to disease phenotypes. These will be based on obtaining the genome wide sequence of 4000 samples from the TwinsUK and ALSPAC cohorts (at 6x sequence coverage), and the exome sequence (protein coding regions and related conserved sequence) of 6000 samples selected for extreme phenotypes. Our studies will focus primarily on cardiovascular-related quantitative traits, obesity and related metabolic traits, neurodevelopmental disorders and a limited number of extreme clinical phenotypes that will provide proof-of-concept for future familial trait sequencing. We will analyse directly quantitative traits in the cohorts and the selected traits in the extreme samples, and also use imputation down to 0.1% allele frequency to extend the analyses to further sample sets with genome wide genotype data. In each case we will investigate indels and larger structural variants as well as SNPs, and use statistical methods that combine rare variants in a locus or pathway as well as single-variant approaches. These TwinsUK samples are a subset of the TwinsUK cohort samples with a BMI>=40 that will be exome sequenced by the Obesity group.

  Study EGAS00001000306

• Hypoxia acts as an environmental cue for the human TRM differentiation program

  Tissue-resident memory T-cells (TRM) provide frontline defense against infectious diseases and contribute to anti-tumor immunity; however, aside from the necessity of TGF-β, knowledge regarding TRM-inductive cues remains incomplete, particularly for human cells. Oxygen tension is an environmental cue that distinguishes peripheral tissues from the circulation and here, we demonstrate that differentiation of human CD8+ T-cells in the presence of hypoxia and TGF-β1 led to the development of a TRM phenotype, characterized by a greater than five-fold increase in CD69+CD103+ cells expressing human TRM hallmarks and enrichment for endogenous human TRM gene signatures, including increased adhesion molecule expression and decreased expression of genes involved in recirculation. Hypoxia and TGF-β1 synergized to produce a significantly larger population of TRM phenotype cells than either condition alone, and comparison of these cells from the individual and combination conditions revealed distinct phenotypic and transcriptional profiles, indicating a programming response to milieu rather than a mere expansion. Our findings identify a previously unreported cue for the TRM differentiation program and can enable facile generation of human TRM phenotype cells in vitro for basic studies and translational applications such as adoptive cellular therapy.

  Study EGAS00001005286

• A recessive PRDM13 mutation results in congenital hypogonadotropic hypogonadism and cerebellar hypoplasia

  The PRDM13 (PR Domain containing 13) putative chromatin modifier and transcriptional regulator functions downstream of the transcription factor PTF1A, which controls GABAergic fate in the spinal cord and neurogenesis in the hypothalamus. Here, we report a novel, recessive syndrome associated with PRDM13 mutation. Patients exhibited intellectual disability, ataxia with cerebellar hypoplasia, scoliosis and delayed puberty with congenital hypogonadotropic hypogonadism (CHH). Expression studies revealed Prdm13/PRDM13 transcripts in the developing hypothalamus and cerebellum in mouse and human. An analysis of hypothalamus and cerebellum development in mice homozygous for a Prdm13 mutant allele revealed a significant reduction in the number of Kisspeptin (Kiss1) neurons in the hypothalamus and PAX2+ progenitors emerging from the cerebellar ventricular zone. The latter was accompanied by ectopic expression of the glutamatergic lineage marker TLX3. Prdm13-deficient mice displayed cerebellar hypoplasia, normal gonadal structure, but delayed pubertal onset. Together, these findings identify PRDM13 as a critical regulator of GABAergic cell fate in the cerebellum and of hypothalamic kisspeptin neuron development, providing a mechanistic explanation for the co-occurrence of CHH and cerebellar hypoplasia in this syndrome. To our knowledge, this is the first evidence linking disrupted PRDM13-mediated regulation of Kiss1 neurons to CHH in humans.

  Study EGAS00001005878

• The Spatial Heterogeneity in Multiple Myeloma - from the Subclonal Architecture to the Immune Microenvironment (partly hipo_K08K)

  Multiple myeloma (MM) cells show pronounced heterogeneity not only within a given patient but also between spatially separated tumor loci in the bone marrow. Understanding this spatial heterogeneity is emerging as a critical challenge for the successful treatment of the disease. Yet, our understanding of spatial differences in the subclonal architecture, molecular signatures and interactions with the tumor microenvironment remains very limited. To address this shortcoming, we performed bulk and single-cell multi-region sequencing, including random bone marrow samples from the iliac crest and paired imaging-guided focal lesion specimens from 15 newly diagnosed MM patients. We found a median of 5 subclones per patient and unique subclones in focal lesions. Central features of spatial heterogeneity included a consistent down-regulation of the chemoattractant cytokines CXCL7 and CXCL12 in focal lesion tumor cells as well as a significant depletion of macrophages in the focal lesion microenvironment. In contrast, a site-specific expansion of T-cell clones was not detected in focal lesions. In conclusion, our results demonstrate the relevance of considering spatial heterogeneity with potential implications for immunotherapies and molecular studies analyzing the role of gene signatures and MM-microenvironment interactions in disease progression.

  Study EGAS00001006090

• Atypical teratoid/rhabdoid tumoroids reveal subgroup-specific drug vulnerabilities WGS

  Atypical teratoid/rhabdoid tumors (ATRTs) represent a rare, but aggressive pediatric brain tumor entity. They are genetically uniquely defined by alterations in the SWI/SNF chromatin remodeling complex members SMARCB1 or SMARCA4. ATRTs can be further classified in different molecular subgroups based on their epigenetic profiles. Although recent studies suggest that the different subgroups have distinct clinical features, subgroup-specific treatment regimens have not been developed thus far. This is hampered by the lack of pre-clinical in vitro models representative of the different molecular subgroups. Here, we describe the establishment of ATRT tumoroid models from the ATRT-MYC and ATRT-SHH subgroups. We demonstrate that ATRT tumoroids retain subgroup-specific epigenetic and gene expression profiles. High throughput drug screens on our ATRT tumoroids revealed distinct drug sensitivities between and within ATRT-MYC and ATRT-SHH subgroups. Whereas ATRT-MYC universally displayed high sensitivity to multi-targeted tyrosine kinase inhibitors, ATRT-SHH showed a more heterogeneous response with a subset showing high sensitivity to Notch inhibitors, which corresponded to high expression of Notch receptors. Our ATRT tumoroids represent the first pediatric brain tumor organoid model, providing a representative pre-clinical model which enables the development of subgroup-specific therapies.

  Study EGAS00001006865

• Atypical teratoid/rhabdoid tumoroids reveal subgroup-specific drug vulnerabilities DNA-Methylation

  Atypical teratoid/rhabdoid tumors (ATRTs) represent a rare, but aggressive pediatric brain tumor entity. They are genetically uniquely defined by alterations in the SWI/SNF chromatin remodeling complex members SMARCB1 or SMARCA4. ATRTs can be further classified in different molecular subgroups based on their epigenetic profiles. Although recent studies suggest that the different subgroups have distinct clinical features, subgroup-specific treatment regimens have not been developed thus far. This is hampered by the lack of pre-clinical in vitro models representative of the different molecular subgroups. Here, we describe the establishment of ATRT tumoroid models from the ATRT-MYC and ATRT-SHH subgroups. We demonstrate that ATRT tumoroids retain subgroup-specific epigenetic and gene expression profiles. High throughput drug screens on our ATRT tumoroids revealed distinct drug sensitivities between and within ATRT-MYC and ATRT-SHH subgroups. Whereas ATRT-MYC universally displayed high sensitivity to multi-targeted tyrosine kinase inhibitors, ATRT-SHH showed a more heterogeneous response with a subset showing high sensitivity to Notch inhibitors, which corresponded to high expression of Notch receptors. Our ATRT tumoroids represent the first pediatric brain tumor organoid model, providing a representative pre-clinical model which enables the development of subgroup-specific therapies.

  Study EGAS00001006881

• EGAD00010000600

  Prostate Adenocarcinomas samples using 450K

  Dataset EGAD00010000600

• Single-Cell RNA-Sequencing Analysis of Responses to Pembrolizumab in Sezary Syndrome

  This phase 2 single arm clinical trial assessed the efficacy of pembrolizumab in patients with previously treated mycosis fungoides or Sezary syndrome. Pembrolizumab was found to have a 38% overall response rate, and a 27% overall response rate in subjects with Sezary syndrome. We performed single-cell RNA-sequencing on samples collected before the first treatment and after 3 weeks of pembrolizumab treatment. Sequencing was performed on cryopreserved peripheral blood T-lymphocytes isolated from 6 trial participants, including 3 patients who responded to pembrolizumab treatment and 3 patients who did not respond. A total of 118,961 peripheral blood T-cells are included in this data set.

  Study phs002933

• Long-read single-cell RNA sequencing uncovers cell-type specific transcript regulation in COVID-19

  SARS-CoV-2 infection leads to extensive host transcriptomic changes, but the role of alternative splicing in shaping the immune response remains underexplored. Here, we present the first application of long-read single-cell RNA sequencing on nasopharyngeal swabs from COVID-19 patients and healthy controls to resolve transcript-level changes across cell types. Leveraging the strengths of long-read sequencing, we characterize alterations in both gene and isoform expression within cell populations of the upper respiratory tract—the primary site of SARS-CoV-2 entry. This approach provides new insights into how transcriptional regulation and splicing shape host immune responses to viral infection.

  Study EGAS50000001290

• Integrative single-cell and cell-free plasma RNA transcriptomics elucidates placental cellular dynamics

  The human placenta is a dynamic and cellular heterogeneous organ, which is critical in fetomaternal homeostasis and the development of preeclampsia. Previous work has shown that placenta-derived cell-free RNA increases during pregnancy. We applied large-scale microfluidic single-cell transcriptomic technology to comprehensively characterize cellular heterogeneity of the human placentas and identified multiple placental cell-type–specific gene signatures. Analysis of the cellular signature expression in maternal plasma enabled noninvasive delineation of the cellular dynamics of the placenta during pregnancy and the elucidation of extravillous trophoblastic dysfunction in early preeclampsia.

  Study EGAS00001002449

• Sequencing of liver cancer cell lines

  Liver cancer is a dreadful disease with limited therapeutic options. How to translate genomic findings into biomarkers and precision treatment is challenging. A large cell line-based platform was established, termed as Liver Cancer Model Repository. Heterogeneities in patients were faithfully recapitulated by 81 liver cancer cell lines at genomic and transcriptomic levels. This platform provides a rich resource and models to study cancer drivers and drug responses in liver cancer.

  Study EGAS00001002237

• Identification of Targetable FGFR Gene Fusions in Diverse Cancers

  In this study, patients with advanced cancer across all histologies were enrolled in our IRB approved clinical sequencing program, called MI-ONCOSEQ, to go through an integrative sequencing which includes whole exome sequencing of the tumor and matched normal, and transcriptome sequencing. Four index cases were identified which harbor gene rearrangements of FGFR2 including two cholangiocarcinoma cases, a metastatic breast cancer case, and a metastatic prostate cancer case. After extending our assessment of FGFR rearrangements across multiple tumor cohorts, including TCGA, we identified FGFR gene fusions with intact kinase domains of FGFR1, FGFR2, or FGFR3 in cholangiocarcinoma, breast cancer, prostate cancer, lung squamous cell cancer, bladder cancer, thyroid cancer, oral cancer, glioblastoma, and head and neck squamous cell cancer. All FGFR fusion partners tested exhibit oligomerization capability, suggesting a shared mode of kinase activation. Overexpression of FGFR fusion proteins in vitro induced cell proliferation, and bladder cancer cell lines that harbors FGFR3 fusion proteins exhibited enhanced susceptibility to pharmacologic inhibition in vitro and in vivo. Due to the combinatorial possibilities of FGFR family fusion to a variety of oligomerization partners, clinical sequencing efforts which incorporate transcriptome analysis for gene fusions are poised to identify rare, targetable FGFR fusions across diverse cancer types.

  Study phs000602

• UK Biobank Access - http://www.ukbiobank.ac.uk/using-the-resource/

  Dac EGAC00001000641

• DEHNRUKE

  Methylation data using 450K

  Dataset EGAD00010001294

• CYTOSCANHD_Genotyping

  samples using Affymetrix CYTOSCANHD

  Dataset EGAD00010000921

• SARS-CoV-2 induced alterations of the upper airway DNA methylome exert long-term impacts on ciliary genes involved in ciliary function

  Enzymatic DNA methylome (n=33) and single-cell RNA (n=24) sequencing were performed in nasal cells of COVID-19 patients and controls. In addition, we re-sampled a subset of patients for transcriptome analyses at 3 and 12 months post-infection and followed the expression of differentially regulated genes over time.

  Study EGAS50000000273

• Whole blood transcriptomics analysis in Antiphospholipid syndrome in patients with Systemic Lupus Erythematosus

  We analyzed whole-blood RNA-sequencing data from 299 SLE patients (108 SLE-aPL-positive, including 67 SLE-APS; 191 SLE-aPL-negative) and 72 matched healthy controls (HC). Pathway enrichment analysis, unsupervised WGCNA analysis and machine learning were applied to distinguish disease endotypes. Deconvolution analysis was performed to characterize the peripheral blood immune cell profile.

  Study EGAS00001007750

• Investigating transcriptional changes in rapidly differentiated iPSC-derived neurons (i3Ns) harbouring the SNCA A53T mutation +/- RSL3

  In this study we performed bulk RNA sequencing of a iPSC-derived rapid neuronal model harbouring the Parkinson's disease associated A53T mutation in SNCA. These neurons were subsequently treated with a low dose of RSL3 (300nM) for 6 hours to establish the transcriptional impact of ferroptosis induction in the presence or absence of SNCA A53T mutation.

  Study EGAS50000001536

• CLUSTER consortium RNAseq CD19 B cell dataset of UK JIA patients.

  This study examines B cell transcriptomic profiles in Juvenile Idiopathic Arthritis (JIA) patients to investigate molecular mechanisms underlying disease heterogeneity. CD19+ B cells were isolated from peripheral blood samples and subjected to RNA sequencing to characterise gene expression patterns. The dataset includes patients with documented uveitis status to enable investigation of B cell contributions to the common JIA comorbidity.

  Study EGAS50000001123

• Single cell RNA sequencing data in "Three-dimensional human alveolar stem cell culture models reveal infection response to SARS-CoV-2"

  This dataset includes a total of 5 single cell RNA sequencing (scRNAseq) data of SARS-CoV-2 infected human alveolar stem cell culture models. Two scRNAseq data were obtained from SARS-CoV-2 infection with MOI of 1.0 (1 for control and 1 for infected case) and the other three were obtained from SARS-CoV-2 infection with MOI of 0.1 in the study entitled "Three-dimensional human alveolar stem cell culture models reveal infection response to SARS-CoV-2". The 10x Chromium Single Cell 3' Reagent kits were used to generate libraries.

  Dataset EGAD00001006242

• Whole genome and RNA-sequencing in T-cell acute lymphoblastic leukemia

  Dataset includes whole genome and transcriptomic sequencing data from five T-cell acute lymphoblastic leukemia (T-ALL) patients. Whole genome sequencing has performed from both diagnostic (T-ALL sample) and control (remission sample) samples. RNA-sequencing has performed from diagnostic samples. Samples has been taken from the bone marrow or peripheral blood.

  Dataset EGAD00001008658

• Transcriptomic profiling of RIRCD patient skeletal muscle, comparing muscle during affected phase to healthy control, and affected patient with and without additional EARS2 mutations.

  Illumina Nextseq total RNA sequencing profiles of skeletal muscle biopsies of 5 affected patients (F3/2M, F4/1F, F5/1M, F2/2F, F2/1M) compared to 6 control (Control040500, Control3509, Control3934, Control3949, Control4994, Control5106) and comparing 3 patients with additional EARS2 mutations (F2/2F, F2/1M, F5/1M) to 2 patients without (F3/2M, F4/1F). Illumina MiSeq total RNA sequencing profiles of skeletal muscle biopsies from patient F3/1M during affected disease phase (4 replicates: F3-1M_Affected_1, F3-1M_Affected_2, F3-1M_Affected_3, F3-1M_Affected_4) compared to recovered phase (F3-1M_Recovered_1, F3-1M_Recovered_2, F3-1M_Recovered_3, F3-1M_Recovered_4).

  Dataset EGAD00001006381

• Whole-genome and transcriptome sequencing of primary cutaneous CD8+ aggressive epidermotropic cytotoxic T-cell lymphoma

  Primary cutaneous CD8+ aggressive epidermotropic cytotoxic T-cell lymphoma (pcAECyTCL) is a rare variant of cutaneous T-cell lymphoma with an aggressive clinical course and a very poor prognosis. We subjected tumor biopsies from patients with pcAECyTCL to whole-genome sequencing and RNA-sequencing to investigate genomic alterations and deregulated gene expression in the disease.

  Study EGAS00001004332

• Molecular profiling of MBD4-deficient acute myeloid leukaemia

  We describe two cases of MBD4-deficient acute myeloid leukaemia (AML). Clinical samples were used for molecular analysis, including genomic profiling (genome and exomes), methylation analysis (RRBS) and transcriptional profiling (RNA-sequencing). An analysis and methodological description has been published: “MBD4 guards against methylation damage and germline deficiency predisposes to clonal hematopoiesis and early-onset AML” [PMID: 30049810]

  Study EGAS00001002581

• Transcriptome sequencing of myelodysplasia

  Transcriptome sequencing was performed on 214 patients with myelodysplasia in this study. RNA was obtained from bone marrow CD34+ cells (n=100) and/or bone marrow mononuclear cells (n=165). Transcriptome sequencing was performed for both cell fractions in 51 patients. We also studied bone marrow CD34+ cells and bone marrow mononuclear cells obtained from three healthy adults each.

  Study EGAS00001002346

• Transcriptomic analysis of TFEB overexpression in LT-HSC, ST-HSC and MEP

  Long-term hematopoietic stem cells (LT-HSC), Short-term hematopietic stem cells (ST-HSC) and Megakaryocyte-erythrocyte progenitors (MEP) were sorted from human cord blood and cultured overnight before transduction with lentivirus to overexpress GP91 (CTRL) or TFEB. Three (LT-HSC ans ST-HSC) or six (MEP) days later, BFP+ transduced cells were sorted for RNA extraction and sequencing.

  Study EGAS00001004969

• Bone marrow derived stromal cells from Myelodysplastic Syndromes

  In this study we performed exome sequencing of bone marrow derived, in-vitro expanded mesenchymal stromal cells from patients with Myelodysplastic Syndromes in order to assess clonal mutations in the non hematopoietic compartment. We used bone marrow mononuclear cells as germline controls. Validation was carried out with amplicon based resequencing. Alongside we provide RNA Sequencing of MDS and healthy MSCs.

  Study EGAS00001005051

• Defective homologous recombination in HCC

  Backgrounds and Aims: We performed an in-depth examination of pathogenic germline (PGVs) and somatic variants in DNA damage response (DDR) genes in hepatocellular carcinoma (HCC) to explore their clinical and genomic impacts. Approach and Results: We used a merged whole exome or RNA sequencing dataset derived from in-house (n=230) and TCGA (n=362) databases of multiethnic HCC samples.

  Study EGAS00001006599

• Germline DNA Methylation Associated with Breast Cancer Predisposition

  Understanding and explaining hereditary predisposition to cancer has focused on the genetic etiology of the disease. However, mutations in known genes associated with breast cancer such as BRCA1 and BRCA2 account for less than 25% of familial cases of breast cancer. Heritable epigenetic modifications, in the form of hypermethylated MLH1 promoter alleles, have recently been shown to promote hereditary nonpolyposis colorectal cancer. We investigated the potential for an epigenetic basis for hereditary breast cancer by performing deep bisulfite sequencing of CpG islands and known promoter regions in germline DNA from 100 familial or early-onset breast or ovarian cancer patients.

  Study phs001699

• Germline pathogenic variant and gastric cancer risk

  Germline pathogenic variants in some genes have been suggested to be associated with gastric cancer risk, although large-scale evaluations were limited. Herein, we analyzed germline variants in 27 cancer-predisposing genes in 10,426 gastric cancer patients and 38,153 controls from BioBank Japan. Following quality control of sequencing data, samples from 10,366 gastric cancer patients and 37,592 controls were further analyzed. We evaluated the association between pathogenic variants and gastric cancer risk and explored the characteristics of the pathogenic-variant carrier. Nine genes were associated with gastric cancer risk. The germline pathogenic variant carriers showed different clinical and demographic characteristics.

  Study JGAS000592

• UK_RCC_GWAS

  Renal cell carcinoma (RCC) cases comprised adult patients with histologically proven RCC were collected through two sources within the UK. First, 856 cases from SORCE, a MRC collection of surgically treated RCC cases ascertained through UK clinical oncology centres. Second, 189 RCC cases collected through the ICR and Royal Marsden NHS Hospitals Trust. Cases included 590 clear cell carcinomas (CCCs), 42 papillary carcinomas (PCs), 33 chromophobe carcinomas (CCs) and 19 mixed or other histological subtypes. DNA was extracted from EDTA-venous blood samples using the conventional methods and quantified using PicoGreen (Invitrogen). Cases were genotyped using the Human OmniExpress-12 BeadChip according to the manufacturer's recommendations (Illumina Inc, San Diego, CA, USA). After strict QC, 944 cases were retained. Data provided in plink format. Controls used were data from the Wellcome Trust Case Control Consortium 2 (WTCCC2) 1958 birth cohort and the UK Blood Service Control Group (available as EGAS00000000028). 

  Dataset EGAD00010002310

• ONGOING CHROMOSOMAL INSTABILITY ACROSS ANEUPLOID SUBTYPES OF CHILDHOOD B-CELL ACUTE LYMPHOBLASTIC LEUKEMIA ASSOCIATES WITH DISEASE PROGRESSION

  Single-cells from primary cB-ALL samples were isolated using an inverted microscope coupled to a micromanipulator equipped with glass capillary for cell collection. A minimum of 20 cells were isolated per sample in microdrops of 2.5 μl of phosphate buffered saline (PBS) with 0.5% polyvinylpyrrolidone. Cell lysis and DNA amplification was performed using the SurePlex DNA Amplification System (Illumina). Genomic DNA was subsequently fragmented and tagged with the VeriSeq PGS transposome and the TruSeq Index adapters by PCR for library preparation (VeriSeq PGS Library Prep Kit, Illumina). Equal volumes of normalized libraries were pooled and sequenced on an Illumina MySeq platform with 1×75-bp single-end sequencing. Reads were subsequently aligned to the human reference genome (GRCh38/hg38) using Bowtie2 (version 2.2.4).

  Dataset EGAD50000000029

• Whole-genome sequences of Korean populations generated by using long- and short-read sequencing technologies.

  We newly sequenced whole-genome of Korean participants by using long- and short-read sequencing platforms (n = 3 and n = 100 for long- and short-read sequencing, respectively). With these data, generated by Sequel II HiFi system (Pacific Bioscience) and DNBSEQ-T7 (MGI) sequencers, we identified a set of structural variations common in Korean population as well as the genetic features distinct from other ethnicities.

  Study EGAS50000000375

• Emirati Genome Project Population Variome (MAF Table)

  The Emirati Genome Project (EGP) Variome comprises allele frequency data derived from 43,608 individuals sequenced as part of the national genome program in the United Arab Emirates. Samples were processed at the M42 EGP Facility and sequenced to a minimum of 30x coverage using Illumina NovaSeq 6000 short-read technology. Variant calling and alignment were performed using the DRAGEN pipeline (v3.9) against the GRCh38 reference genome. This dataset contains a total of 421,605,069 short variants (SNVs and indels), stored in VCF format. Each variant is annotated with population-level metrics in the INFO field, including: AC (alternate allele count) AF (alternate allele frequency) RC (reference allele count) RF (reference allele frequency) For convenience, VCF files are split by chromosome (chr1–22, X, Y), compressed and indexed using bgzip and tabix.

  Dataset EGAD50000001558

• Predicting resistance to chemotherapy using chromosomal instability signatures

  The aim of this study is to assess whether three chromosomal instability signature biomarkers are capable of predicting resistance to standard chemotherapies, namely platins, taxanes and anthracyclines. As part of this study we compiled a proof of principle cohort of ovarian cancers treated with these therapies, profiled using the Illumina TSO500 panel. Analysis of these data demonstrated that accurate biomarker calling can be computed from these gene panel data.

  Study EGAS50000000992

• Flexible and rapid validation of structural variants using adaptive sampling

  The goal of the study is to confirm and further characterize structural variants and complex genomic rearrangements using adaptive sampling with Oxford Nanopore Sequencing. Individuals with known structural variants were included in the study and the known rearrangement regions were targeted in the sequencing experiments. In addition to long-read coverage over the targeted regions (around 25X coverage), the rest of the genome is covered by short off-target reads (around 5X coverage).

  Study EGAS50000001279

• EstMB cohort participants sequenced with MGISEQ-2000 platform

  Participants collected a fresh stool sample immediately after defecation using a sterile Pasteur pipette and placed it in a 15 mL conical polypropylene tube. They were instructed to collect the sample as close as possible to their study center visit. Samples were transported and stored at −80 °C until DNA extraction. Microbial DNA was extracted from 200 mg of stool using a QIAamp DNA Stool Mini Kit (Qiagen), following manufacturer's instructions, after all samples were collected. DNA was quantified using a Qubit 2.0 Fluorometer with a dsDNA Assay Kit (Thermo Fisher Scientific). Library preparation and circularization of equimolarly pooled libraries were done with MGIEasy FS DNA Library Prep Set (MGI Tech Co, Ltd, Shenzhen, China) according to the standard protocol. The sequencing was performed with MGISEQ-2000 High-throughput Sequencing Set (FCL PE150) according to the manufacturer’s instructions (MGI Tech, Shenzhen, China)

  Dataset EGAD50000002213

• Variant calls for "Quality of Whole Genome Sequencing from Blood versus Saliva Derived DNA in Cardiac Patients"

  Paired blood and saliva samples from five unrelated individuals were directly compared for quality of whole genome sequencing. Two (Sample Pairs 1 and 2) were female probands diagnosed with tetralogy of Fallot, a type of congenital heart disease, and three (Sample Pairs 3, 4 and 5) were male probands diagnosed with hypertrophic cardiomyopathy. WGS was performed using Illumina HiSeq X to a target average coverage depth of 30x and a read length of 150 bp. The resulting reads were not filtered for minimum quality in order to avoid losing possible contaminant reads. Sequencing read alignment was done using Isaac Aligner to human genome build hg19. Short variant i.e. single-nucleotide variant (SNV) and small insertion-deletion (indel) calling was performed using Isaac Variant Caller with default parameters.

  Dataset EGAD00001005772

• Profiling of 27 type 2 diabetes GWAS loci using next-generation (NG) capture C in a human beta-cell model

  Most type 2 diabetes association signals are due to variants that impact gene regulation but identifying the genes they impact is challenging. We generated interaction profiles at 27 T2D GWAS loci using next-generation (NG) capture C in a human beta-cell model ( EndoC-betaH1) and contrasted our maps with public Hi-C/promoter capture Hi-C maps in EndoC-betaH1 cells or human islets.

  Study EGAS00001006105

• Breast Cancer Susceptibility

  Genetic factors account for a large fraction of breast cancer risk and it is estimated that up to 30% of breast cancers have a heritable component. Inherited cancer susceptibility is associated with early-onset of malignancies in general. Although 20% of young women with breast cancer have germline mutations in the best understood breast cancer susceptibility genes, BRCA1, BRCA2 and TP53, in the remaining 80% of women with early-onset breast cancer, the genetic factors contributing to disease remain unexplained. By studying the extreme phenotype of women diagnosed at an early age there is enrichment for genetic factors that contribute to breast cancer. This study contains the whole exome sequence of 384 women diagnosed with invasive breast cancer prior to 40 years of age. Each of the subjects reported a family history of breast cancer and lacked mutations in BRCA1 and BRCA2.

  Study phs001017