3334 results for "*geneti*"

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• DNA methylation-based classification of sinonasal tumors [Proteomics data]

  The diagnosis of sinonasal tumors is challenging due to a heterogeneous spectrum of various differential diagnoses as well as poorly defined, disputed entities such as sinonasal undifferentiated carcinomas (SNUCs). In this study, we apply a machine learning algorithm based on DNA methylation patterns to classify sinonasal tumors with clinical-grade reliability. We further show that sinonasal tumors with SNUC morphology are not as undifferentiated as their current terminology suggests but rather reassigned to four distinct molecular classes defined by epigenetic, mutational and proteomic profiles. This includes two classes with neuroendocrine differentiation, characterized by IDH2 or SMARCA4/ARID1A mutations with an overall favorable clinical course, one class composed of highly aggressive SMARCB1-deficient carcinomas and another class with tumors that represent previously misclassified adenoid cystic carcinomas. The repository includes the raw mass spectrometry-based proteomics data

  Study EGAS00001006712

• DNA methylation-based classification of sinonasal tumors [DNA sequencing]

  The diagnosis of sinonasal tumors is challenging due to a heterogeneous spectrum of various differential diagnoses as well as poorly defined, disputed entities such as sinonasal undifferentiated carcinomas (SNUCs). In this study, we apply a machine learning algorithm based on DNA methylation patterns to classify sinonasal tumors with clinical-grade reliability. We further show that sinonasal tumors with SNUC morphology are not as undifferentiated as their current terminology suggests but rather reassigned to four distinct molecular classes defined by epigenetic, mutational and proteomic profiles. This includes two classes with neuroendocrine differentiation, characterized by IDH2 or SMARCA4/ARID1A mutations with an overall favorable clinical course, one class composed of highly aggressive SMARCB1-deficient carcinomas and another class with tumors that represent previously misclassified adenoid cystic carcinomas. This repository includes the results from DNA sequencing and mass spectrometry-based proteomics.

  Study EGAS00001006713

• The Iberian Roma genetic variant server

  The Roma are the most numerous ethnic minority in Europe. The Iberian Roma arrived in the Iberian Peninsula five centuries ago and still today, they keep a strong group identity. Demographic and cultural reasons lie behind a high rate of Mendelian disease often related to founder variants. We have analysed exome data from 119 Iberian Roma individuals collected from 2018 to 2020. A database of variant frequency has been implemented (IRPVS) and made available online. We have analysed the carrier rate of founder private alleles as well as pathogenic variants present in the general population. Significant enrichment in structural variants involving gene clusters related to keratinization and epidermal growth suggest that evolutive mechanisms have developed towards climate and environmental adaptation. IRPVS can be accessed at http://irpvs.clinbioinfosspa.es/

  Study EGAS00001006758

• Host pathogen interaction long read transcriptome

  Our incomplete knowledge of the human transcriptome impairs the detection of disease-causing variants, in particular in transcripts only expressed under certain conditions. These transcripts are often lacking from reference transcript sets, such as Ensembl/GENCODE and RefSeq, and could be relevant for establishing genetic diagnoses. We present SUsPECT (Solving Unsolved Patient Exomes/gEnomes using Custom Transcriptomes), a pipeline based on the Ensembl Variant Effect Predictor (VEP) to predict variant impact on custom transcript sets, such as those generated by long-read RNA-sequencing, for downstream prioritization. Our pipeline predicts the functional consequence and likely deleteriousness scores for missense variants in the context of novel open reading frames predicted from any transcriptome. We demonstrate the utility of SUsPECT by uncovering potential mutational mechanisms of pathogenic variants in ClinVar that are predicted to be benign using the reference transcript annotation. In further support of SUsPECT’s utility, we identified an enrichment of immune-related variants predicted to have a more severe molecular consequence when annotating with a newly generated transcriptome from stimulated immune cells instead of the reference transcriptome. Our pipeline outputs crucial information for further prioritization of potentially disease-causing variants for any disease and will become increasingly useful as more long-read RNA sequencing datasets become available.

  Study EGAS00001006779

• Highly sensitive liquid biopsy Duplex sequencing complements tissue biopsy to enhance detection of clinically relevant genetic variants

  Study EGAS00001006805

• Exome sequencing of HCV+ lymphoma

  The present retrospective study aimed to explore the genetic landscape of a well-characterized series of 34 HCV-associated B-cell lymphomas from the observational multicentric ANRS HC-13 Lympho-C Study using tumor and matched germline whole exome sequencing (WES). It reported the first series of VHC-positive lymphoma patients analyzed by WES. Our results provide an overview of the genetic landscape associated to HCV-related B-cell lymphomas and highlight some novel putative candidate genes.

  Study EGAS00001006860

• Erythroid/megakaryocytic differentiation confers BCL-XL dependency and venetoclax resistance in acute myeloid leukemia

  Myeloid neoplasms with erythroid or megakaryocytic differentiation include pure erythroid leukemia (PEL), myelodysplastic syndrome (MDS) with erythroid features, and acute megakaryoblastic leukemia (FAB M7) and are characterized by poor prognosis and limited treatment options. Here, we investigate the drug sensitivity landscape of these rare malignancies. We show that acute myeloid leukemia (AML) cells with erythroid or megakaryocytic differentiation depend on the anti-apoptotic protein BCL-XL, rather than BCL-2, using combined ex vivo drug sensitivity testing, genetic perturbation, and transcriptomic profiling. Single-cell and bulk transcriptomics of patient samples with erythroid and megakaryoblastic leukemias identified high BCL2L1 expression compared to other subtypes of AML and other hematological malignancies, where BCL2 and MCL1 were more prominent. Our results suggest targeting BCL-XL as a potential therapy option in erythroid/megakaryoblastic leukemias and highlight an AML subgroup with potentially reduced sensitivity to venetoclax-based treatments.

  Study EGAS00001006819

• HLA-DR is absent in primitive macrophages through epigenetic silencing of master regulator CIITA

  The earliest macrophages are generated during embryonic development from erythro-myeloid progenitors (EMPs) via primitive haematopoiesis. This process is poorly understood in humans and in the mouse is thought to be spatially restricted to the yolk sac. Human fetal placental macrophages, Hofbauer cells (HBC), arise during the primitive haematopoietic wave at ~18 days post conception. Here we identify a population of placental erythro-myeloid progenitors (PEMPs) in the early human placenta that give rise to HBC. PEMP are fetal CD34+CD43+ progenitors found exclusively at early gestational timepoints. Transcriptomic analyses reveal that PEMP have conserved features of primitive yolk sac EMPs, including the lack of HLF expression. Using in vitro single-cell culture experiments we show that PEMP generate HBC-like cells that completely lack HLA-DR expression  and demonstrate that this is a conserved feature of all macrophages generated by primitive haematopoiesis in humans. Finally, we demonstrate that the class II transactivator, CTIIA, the master regulator HLA-DR expression, is epigenetically silenced during primitive haematopoiesis, leading to HLA-DRneg macrophages. These findings demonstrate that HBC are derived locally from PEMP and establish the human placenta as an additional site of primitive haematopoiesis.

  Study EGAS00001006981

• Identifying rare genetic variants in 21 highly multiplex autism families

  Study EGAS00001006928

• CYP2C19 long-read sequencing

  Inter-individual differences in drug response based on genetic variations can lead to drug toxicity and treatment inefficacy. A large part of this variability is caused by genetic variants in pharmacogenes. Unfortunately, the Single Nucleotide Variant (SNV) panels currently used in clinical pharmacogenomic (PGx) testing are unable to detect all genetic variability in these genes. Long-read sequencing, on the other hand, has been shown to be able to resolve complex (pharmaco)genes. In this study we have assessed the added value of long-read sequencing for PGx focusing on the clinically important and highly polymorphic CYP2C19 gene. With a capture-based long-read sequencing panel we were able to characterize the entire region and assign variants to their allele of origin (phasing), resulting in the identification of 813 unique variants in 37 samples. To assess the clinical utility of this data we have compared the performance of three different *-allele tools (Aldy, PharmCat and PharmaKU) which are specifically designed to assign clinical haplotypes to pharmacogenes based on all input variants. We conclude that long-read sequencing can improve our ability to characterize the CYP2C19 locus, help to identify novel haplotypes and that *-allele tools are an useful asset in phenotype prediction. Ultimately, this approach could help to better predict an individual’s drug response and improve therapy outcomes.

  Study EGAS00001006929

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

  Study EGAS00001007008

• Timing chromosomal amplification events using patterns of somatic mutations in high hyperdiploid acute lymphoblastic leukemia

  This dataset included samples with high hyperdiploid acute lymphoblastic leukemia (ALL) collected from the Division of Clinical Genetics, Lund University, Sweden. All samples were subjected to whole genome sequencing using the Illumina HiSeqX platform. Paired-end sequencing (2x150bp) was done to ~60x coverage for diagnostic samples and ~30x coverage for remission samples. The paired-end reads were aligned to the human reference genome GRCh37 (https://www.ncbi.nlm.nih.gov/assembly/GCF_000001405.25/) by the Burrows-Wheeler Aligner tool (version 0.7.17). Duplicate reads marking and local realignment were performed by GATK (version 4.0.11.0).

  Study EGAS00001007052

• Genetic heritage of the Baphuthi highlights an over-ethnicised notion of 'Bushman' in the Maloti-Drakensberg, southern Africa

  Using contemporary people as proxies for ancient communities is a contentious but necessary practice in anthropology. In southern Africa, the distinction between the Cape KhoeSan and eastern KhoeSan remains unclear as ethnicity labels have been changed through time and most communities were decimated if not extirpated. The eastern KhoeSan may have had genetic distinctions from neighbouring communities who speak Bantu languages and KhoeSan further away, alternatively the identity may not have been tied to any notion of biology, instead denoting communities with a nomadic 'lifeway' distinct from African agro-pastoralism. The Baphuthi of the 1800s in the Maloti-Drakensberg, southern Africa had a substantial KhoeSan constituency and a lifeway of nomadism, cattle raiding, and horticulture. Baphuthi heritage could provide insights into the history of the eastern KhoeSan. We examine genetic affinities of 23 Baphuthi to discern whether the narrative of KhoeSan descent reflects distinct genetic ancestry. Genome-wide SNP data (Illumina GSA) were merged with 52 global populations, for 160K SNPs. Genetic analyses show no support for a unique eastern KhoeSan ancestry distinct from other KhoeSan or southern Bantu-speakers. The Baphuthi have strong affinities with early-arriving southern Bantu-speaking (Nguni) communities, as the later-arriving non-Nguni show strong evidence of recent African admixture possibly related to Late-Iron Age migrations. The references to communities as 'San',and 'Bushman' in historic literature has often been misconstrued as notions of ethnic/biological distinctions. The terms may have reflected ambiguous references to non-sedentary polities instead, as seems to be the case for the eastern ‘Bushman’ heritage of the Baphuthi.

  Study EGAS00001007080

• Long-term organoid culture of a small intestinal neuroendocrine tumor rna-seq

  Gastroenteropancreatic neuroendocrine tumors (GEP-NETs) are rare and highly heterogeneous neoplasms whose incidence has markedly increased over the last decades. A grading system based on the tumor cells' proliferation index predicts high-risk for G3 NETs. However, low-to-intermediate grade (G1/G2) NETs have an unpredictable clinical course that varies from indolent to highly malignant. Cultures of human cancer cells enable to perform functional perturbation analyses that are instrumental to enhance our understanding of cancer biology. To date, no tractable and reliable long-term culture of G1/G2 NET has been reported to permit disease modeling and pharmacological screens. Here, we report of the first long-term culture of a G2 metastatic small intestinal NET that preserves the main genetic drivers of the tumor and retains expression patterns of the endocrine cell lineage. Replicating the tissue, this long-term culture showed a low proliferation index, and yet it could be propagated continuously without dramatic changes in the karyotype. The model was readily available for pharmacological screens using targeted agents and as expected, showed low tumorigenic capacity in vivo. Overall, this is the first long-term culture of NETs to faithfully recapitulate many aspects of the original neuroendocrine tumor.

  Study EGAS00001007108

• IL7-receptor expression is frequent in T-cell acute lymphoblastic leukemia and predicts sensitivity to JAK-inhibition

  T-cell acute lymphoblastic leukemia (T-ALL) is an aggressive hematological malignancy with a dismal prognosis related to refractory/relapsing diseases, raising the need for new targeted-therapies. Activating mutations of the IL7-receptor pathway genes (IL7Rp) play a proven leukemia-supportive role in T-ALL. JAK-inhibitors such as ruxolitinib have recently demonstrated preclinical efficacy. However, prediction markers for sensitivity to JAK-inhibitors are still lacking. Herein, we show that IL7R (CD127) expression is more frequent (~70%) than IL7Rp-mutations in T-ALL (~30%). We compared the so-called non-expressers (no IL7R-expression/IL7Rp-mutation), expressers (IL7R-expression without IL7Rp-mutation) and mutants (IL7Rp-mutations). Integrative multi-omics analysis outlined IL7R-deregulation in virtually all T-ALL subtypes, at the epigenetic-level in non-expressers, genetic-level in mutants, and post-transcriptional level in expressers. Ex-vivo data using primary-derived xenografts support that IL7Rp is functional whenever the IL7R is expressed, regardless of the IL7Rp mutational status. Consequently, ruxolitinib impaired T-ALL survival in both expressers and mutants. Interestingly, we show that expressers displayed ectopic IL7R-expression and IL7Rp-addiction conferring a deeper sensitivity to ruxolitinib. Conversely, mutants were more sensitive to venetoclax than expressers. Overall, combination of ruxolitinib and venetoclax resulted in synergistic effects in both groups. We illustrate the clinical relevance of this association by reporting achievement of complete remission in two patients with refractory/relapsed-T-ALL. This provides proof of concept for translation of this strategy into clinics as bridge to transplant. Altogether, IL7R-expression can be used as a biomarker for sensitivity to JAK-inhibition, thereby expanding the fraction of T-ALL patients eligible to ruxolitinib up to nearly ~70% of T-ALL.

  Study EGAS00001007144

• Genomic map of Poland in open access - digitization of biomolecular resources of the Biobank University of Lodz laboratory

  The aim of the project is to create infrastructure for free access to digitized resources. The data comes from the resources of the Biobank WBiOŚ University of Lodz laboratory and concerns human genetics. A fragment of the POPULOUS collection will be digitized - a collection of biological material collected from Polish residents, reflecting the demographic structure of the country. The final products will be digitized full genomes and full exons of Poles from 750 anonymous donors from a group of over 10,000 volunteers.

  Study EGAS50000000154

• Epigenetic Modifications and Their Role in Human Disease: A Genomic Perspective on Inherited and Environmental Factors

  Epigenetic Modifications and Their Role in Human Disease: A Genomic Perspective on Inherited and Environmental Factors

  Study EGAS50000000374

• Unraveling Rare Genetic Variants: Insights from Whole-Genome Sequencing in Precision Medicine

  Unraveling Rare Genetic Variants: Insights from Whole-Genome Sequencing in Precision Medicine

  Study EGAS50000000373

• Swiss demo study

  The Swiss FEGA (Federated European Genome Archive) demonstration project focuses on whole genome sequencing to enable secure and federated data sharing for genomic research. This initiative integrates genomic data across institutions while preserving privacy and regulatory compliance. By employing federated learning, it allows researchers to access insights without transferring sensitive data, ensuring patient confidentiality. The project exemplifies advanced genomic collaboration, supporting studies on population genetics, rare diseases, and personalized medicine. It serves as a model for ethical and efficient genomic data utilization in research.

  Study EGAS50000000404

• EGAD00010000807

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

  Dataset EGAD00010000807

• EGAD00010000831

  BLUEPRINT EpiMatch: harnessing epigenetics for haematopoietic stem cell transplantation

  Dataset EGAD00010000831

• Genetic and epigenetic characterization of adenoid cystic carcinoma

  Whole genome sequences of ACC primagrafts, Histone modification maps and transcription factor binding maps for ACC primagrafts and primary tumors. Processed ChIP-seq data is available on GEO under accession number GSE76465.

  Dataset EGAD00001001662

• Low coverage whole-genome sequencing of samples from the Cretan Greek isolate collection HELIC-MANOLIS

  Whole-genome sequencing at 1x of samples from the Cretan Greek isolate collection HELIC-MANOLIS. Genome-wide association studies of complex traits have been successful in identifying common variant associations, but a substantial heritability gap remains. The field of complex trait genetics is shifting towards the study of low frequency and rare variants, which are hypothesised to have larger effects. The study of these variants can be empowered by focusing on isolated populations, in which rare variants may have increased in frequency and linkage disequilibrium tends to be extended. This work focuses on an isolated population from Crete, Greece. Sequencing is very efficient in isolated populations, because variants found in a few samples will be shared by others in extended haplotype contexts, supporting accurate imputation.

  Dataset EGAD00001001637

• EGAD00010000536

  21 unlinked autosomal microsatellite loci for 30 Central Asian populations

  Dataset EGAD00010000536

• EGAD00010000538

  28 unlinked autosomal microsatellite loci for 20 African and 4 philippine populations

  Dataset EGAD00010000538