4015 results for "*geneti*"

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• Genetic architecture of disease in Greenland is shaped by demographic history, fine-structure, and selection - MEGA chip data

  This data was generated as part of the project titled "Genetic architecture of disease in Greenland is shaped by demographic history, fine-structure, and selection." The study was carried out to investigate the genetic architecture of the Greenlandic population and the consequences it has for disease mapping, diagnosis and prediction.

  Study EGAS50000000658

• Multimodal epigenetic sequencing analysis of cell-free DNA identifies biomarkers for ALS diagnosis and progression

  The role of the circulating epigenome in ALS remains understudied. We aim to develop diagnostic and prognostic blood-based biomarkers for Amyotrophic Lateral Sclerosis (ALS) by profiling methylome signatures in circulating cell-free DNA (cfDNA) in 20 sporadic ALS cases, 10 C9orf72-associated ALS cases, 10 asymptomatic C9orf72 expansion carriers, and 21 healthy controls using targeted enzymatic methyl-sequencing (EM-seq) of ~4 million CpG loci. We detected numerous differentially methylated genes, including several implicated in ALS risk and pathobiology, and integrated multiple epigenetic features with our Multimodal Epigenetic Sequencing Analysis (MESA) algorithm, achieving an ROC AUC of 0.91 and detecting ~70% of ALS cases at ~100% specificity. Methylation at a subset of loci also correlated with clinical progression and cerebrospinal-fluid neurofilament levels, supporting the potential of cfDNA-based biomarkers for ALS diagnosis and monitoring.

  Study EGAS50000001267

• Malignant mesothelioma EWAS on European prospective study

  Study EGAS00001006432

• Cell-free DNA methylation profiling for non-invasive detection and classification of lymphoma

  Compared with traditional tissue biopsies used for lymphoma diagnosis, cell-free DNA methylation profiling offers a minimally invasive approach capable of capturing lymphoma-specific epigenetic alterations. This study investigates genome-wide methylation patterns in plasma using cell-free methylated DNA immunoprecipitation and sequencing (cfMeDIP-seq). Differential methylation analysis of discovery samples identified lymphoma-associated hypermethylated regions that were used to develop classification models for lymphoma detection. Validation analyses demonstrated high accuracy and strong associations between cfDNA methylation scores and independent measures of tumor burden and clinical outcome. These findings support cfDNA methylation profiling as a sensitive approach for non-invasive lymphoma diagnosis.

  Study EGAS50000001463

• Huch Lab, Max Planck Institute of Molecular Cell Biology and Genetics

  Dac EGAC50000000112

• Shaping the Genetic Landscape of Northeast India

  The genetic landscape of South Asia is intriguing. In a vast geographical region like India, mostly genes follow geography. Moreover, at neighbouring regions like East and Southeast Asia, language is the major denominator of the genes. However, these are not just the two alternatives, in many geographical pockets, ethnicity plays a stronger role than either of these. Being a crossroad of South and Southeast Asia, the Himalayan region is mostly populated by the people speaking the Trans-Himalayan language. Archaeological and anthropological studies suggest migration and cultural diffusion in this region with the Tibetan plateau in the North. To understand this complex pattern, we have performed a fine-grained genetic analysis of the major Mizo population and its various clans living at the Himalayan geography. We have investigated 110 individuals belonging to seven different clans of Mizo people for hundred thousand of autosomal markers. In contrast to the East and Southeast Asian genetic landscape, our results suggested that the fine-scaled genetic structure of Northeast India is much more complex and mixture of interplay between languages, ethnicity and geography. Allelic frequency-based analyses indicated that a novel Trans-Himalayan ancestry unite all the populations of this region.

  Study EGAS00001008205

• Epigenetic reprogramming shapes monocytes and heterologous T cell derived cytokine responses in BCG vaccination

  Study EGAS00001007498

• Multi-omic data of subjects of FUSION study

  Finland-United States Investigation of NIDDM Genetics (FUSION) Study has sought to understand the genetic basis of type 2 diabetes (T2D) and diabetes-related traits including glucose, insulin, lipid levels, and obesity. We have performed extensive multi-omic characterization of the study subjects, including SNP array genotyping, whole genome/exome DNA sequencing of blood/tissue/iPSC cells generated from fibroblast, as well as RNAs. The study has provided crucial data for understanding molecular and cellular mechanisms of the disease-causing variants and their respective target genes. This set of data will be a valuable resource to the T2D community.

  Study EGAS00001008440

• Interferon-related inflammaging links epigenetic age acceleration to multimorbidity

  Study EGAS00001008029

• Interferon-related inflammaging links epigenetic age acceleration to multimorbidity

  Study EGAS00001008030

• Interferon-related inflammaging links epigenetic age acceleration to multimorbidity

  Study EGAS00001008031

• RNA sequencing data and whole exome sequencing data of genetically modified IDH1 wildtype and mutant chondrosarcoma cell lines

  This dataset contains total RNA sequencing (polyA enriched) data of early and late passages of n=5 vector-based CH2879 empty vector and IDH1mut cell lines. Total RNA sequencing (polyA enriched) using 150bp paired-end reads was performed in triplicate using the NEBNext Ultra II Directional RNA Library Prep Kit (New England Biolabs) on the NovaSeq6000 platform (Illumina). Additionally, this dataset contains whole exome sequencing data of n=15 parental, mock, and CRISPR-edited IDH1mut and IDH1wt CH2879 and JJ012 cell lines. Whole exome sequencing using 150bp paired-end reads with a minimum coverage of 100x was performed in single using the SureSelect Human All Exon V8 library (Agilent Technologies) on the NovaSeq X platform (Illumina).

  Dataset EGAD50000002703

• Screening for Prostate Cancer-Specific Differentially Methylated Regions Based on BSAC

  Bisulfite Amplicon Sequencing on tissue samples from prostate cancer, benign prostatic hyperplasia (BPH), and bladder cancer.

  Study EGAS50000001895

• Screening for Prostate Cancer-Specific Differentially Methylated Regions Based on MeDIP-seq

  Methylated DNA Immunoprecipitation Sequencing (MeDIP-seq) on tissue samples from prostate cancer, benign prostatic hyperplasia (BPH), and bladder cancer.

  Study EGAS50000001894

• Differential Wnt/β-Catenin Signaling Activities Shape Distinct Tumor Cell Phenotypes

  By profiling patient-derived hepatoblastoma organoids via single-cell transcriptomics and chromatin dynamics, we identify subtype-specific transcriptional and epigenetic profiles. Using CUT&RUN, we show that β-catenin engages distinct genomic regions, which is dictated by differential association with TCF/LEF family transcription factors. TCF7L2 binds to a motif, distinct from the classical Wnt consensus sequence, which is found in the promoter of hepatic target genes.

  Study EGAS50000001229

• Full AfricanNeo ModernDNA Study

  With the largest genomic dataset to date of Bantu-speaking populations, including newly generated data of modern-day and ancient DNA from previously unsampled regions in Africa, we shed fresh light on the expansion of peoples speaking Bantu languages that started ~4000 years ago in western Africa. We have genotyped 1,763 participants, including 1,487 Bantu speakers from 143 populations across 14 African countries. Our comprehensive genetic analysis of the expansion of people speaking Bantu languages reveals a complex history of serial founder events, variable levels of contact with local groups, and spread-over-spread events.

  Study EGAS50000000006

• Integrating transcriptional regulatory networks with chromatin accessibility as markers of survival outcome and drug response in triple-negative breast cancer

  Patients with triple-negative breast cancer (TNBC), a highly aggressive and heterogeneous breast cancer subtype, have limited effective targeted therapy options and frequently develop resistance to chemotherapy. Transcription regulators (TRs) guided precision medicine, namely anti-estrogen receptor therapy, has proven successful in hormone-dependent breast cancer, but remains a challenge in TNBC. Here, we identified key TRs underlying TNBC identity by combining a transcriptional interaction network with chromatin accessibility and defined TR activity score metrics. We show that the activity scores of these TRs independently discriminate patient outcome across different clinical endpoints. Matching TR activity scores to drug sensitivity identified drug-TR pairs across independent datasets, including NFE2L3 and CBFB activity associated with sensitivity to mTOR inhibition, which we validated using a cohort of TNBC patient-derived xenografts. Collectively, we present methodology to promote TR-guided precision medicine that captures inter-tumor heterogeneity in TNBC and nominates drug sensitivities according to TR activity scores inferred from expression and chromatin accessibility data.

  Study EGAS50000001691

• Molecular Landscape of Hypertrophic Cardiomyopathy Across Disease Stages and Genotypes

  Hypertrophic Cardiomyopathy (HCM) is marked by asymmetric cardiac wall thickening, enhanced contractility, diastolic dysfunction, and fibrosis. Pathogenic sarcomere gene variants cause HCM, but comparable abnormalities occur in patients with unexplained disease albeit with fewer adverse events. We applied single-nucleus RNA sequencing to investigate how genetic and unexplained HCM affect early disease mechanisms and to contrast HCM with dilated cardiomyopathy (DCM). This EGA dataset contains HCM and control data. DCM and additional control snRNA-seq data, integrated in this study, are available under the EGA dataset accession number: EGAD00001009292.

  Study EGAS50000001411

• Long-read single-cell genome, transcriptome and open chromatin profiling links genotype to phenotypes

  Current single-cell multiomics methods typically provide limited genomic information, constraining genotype-phenotype studies. To address this gap, we developed SPLONGGET (Single-cell Profiling of LONG-read Genome, Epigenome, and Transcriptome), which integrates 10X Genomics barcoding with Oxford Nanopore sequencing to simultaneously profile genome, chromatin accessibility, and full-length transcriptomes in thousands of single cells. By retaining all tagmentation fragments during library preparation, SPLONGGET delivers whole-genome coverage, supports target enrichment for effective single-cell genotyping, and remains backwards compatible with existing short-read workflows. We apply SPLONGGET to longitudinal samples from a case of pediatric B-cell acute lymphoblastic leukemia (B-ALL) to reveal clonal dynamics during therapy and the phenotypic effects of somatic variation, providing valuable insights into disease progression and relapse. In conclusion, SPLONGGET enables integrated high-throughput analysis of genetic variation and molecular phenotypes using off-the-shelf kits, offering a timely and powerful tool to study genetically heterogeneous samples, such as tumours but also ageing normal tissues.

  Study EGAS50000001278

• Raw fastq files (not trimmed) from RNAseq sequencing

  Samples from infants diagnosed with KMT2A-r B-ALL confirmed by comprehensive immunophenotypic and molecular/cytogenetic features. Mononuclear cells containing >87% blasts were isolated by density gradient centrifugation. Immunophenotyping was performed using the monoclonal antibodies CD45-FITC, CD19-APC, and NG2-PE. NG2POS (NG2 positive) and NG2NEG (NG2 Negative) B-ALL blasts (CD45dimCD19+) were sorted by fluorescence-activated cell sorting (FACS) using a FACS-Aria Fusion cell sorter (BD Biosciences).

  Study EGAS50000001244

• Proteomics of human cancer-associated T cells identifies regulators of T cell functionality

  CD8⁺ T cells in solid tumors progressively lose anti-tumor activity, yet the cell-intrinsic mechanisms driving this loss of function remain incompletely defined. Here, we performed matched proteomic and transcriptomic profiling of dysfunctional and bystander CD8⁺ tumor-infiltrating T cells isolated from primary tumors of treatment-naïve non-small cell lung cancer patients. Proteomic analysis revealed widespread discordance with mRNA expression, with 8% of differentially expressed proteins detected exclusively at the protein level. Genetic perturbation of such differentially expressed proteins identified the chromatin remodeler CHD4 and fatty acid synthase (FASN) as cell-intrinsic regulators of T cell function. CHD4 deletion promoted effector differentiation and enhanced cytokine production, whereas FASN deletion preserved mitochondrial fitness and sustained T cell functionality under chronic T cell receptor stimulation. Together, these findings demonstrate that proteomic profiling uncovers regulators of T cell functionality that are not apparent from transcriptomic analyses alone, highlighting an additional layer of regulatory control.

  Study EGAS50000001886

• Frequency and prognostic significance of genetic abnormalities in a subgroup of intermediate risk neuroblastoma patients: A SIOPEN study

  Intermediate risk neuroblastoma includes a rare subgroup of patients over the age of 18 months at diagnosis with unresectable, localised tumours with unfavourable histology without MYCN amplification. This group is treated differently around the world with some patients receiving upfront myeloablative therapy (MAT) in addition to standard treatment with chemotherapy, surgery, radiotherapy and 13 cis retinoic acid, but the overall 5-year patient survival with or without MAT is similar (75%). This study aimed to understand the neuroblastoma biology of this rare patient subgroup.

  Study EGAS50000001908

• After the completion of CINECA, EUCANCan, and euCanSHare. What's next?

  CINECA, EUCANCan, and euCanSHare were part of the EUCAN Cluster, made up of six projects that received funding under the same Horizon 2020 call. All EUCAN projects (CINECA, EUCANCan, EUCAN-Connect, euCanSHare, Receptor Plus, and ReCoDID) were aimed at facilitating data reuse and knowledge discovery by enhancing data exchange and long-term collaboration in the health field. Here are some highlights about EGA’s contribution to these projects. CINECA: advances in Federated discovery and infrastructure for cohorts CINECA (Common Infrastructure for National Cohorts in Europe, Canada, and Africa) developed a federated cloud-based infrastructure for making genomic and biomolecular data accessible. The project has assembled a virtual cohort of 1.4 million individuals from sources such as the EGA, CanDIG and H3Africa. The EGA–CRG co-leaded a work package Work Package 1 on Federated Data Discovery and Querying. Beacon v2, championed by Jordi Rambla and Lauren Fromont, has been one of the central elements for the discovery of human genetic and phenotypic data. The EGA-CRG contributed to the development of a model for cohort discovery inside the Beacon v2 model. The team also delivered a Discovery Portal was implemented to explore cohorts and individuals of synthetic data. It is a UI that gathers a network of Beacons, a service for query expansion, and a visualisation tool. Have a look at the Discovery Portal UI, gathering a network of Beacons. You will find entities such as the Barcelona Supercomputing Center (BSC), BioData.pt and the European Genomic Data Infrastructure (GDI), among others. euCanSHare: facilitation of data access management This joint EU-Canada project aimed to build a European and Canadian FAIR platform for cardiovascular data sharing and analysis. The EGA’s tasks contributed to the development of the data management plan and data flows, main web-portal and interoperability protocols. An important part of the EuCanShare platform is the data access manager, a tool for the data owners to control the access to their sensitive datasets. We built a user-friendly interface for data access committees (data owners) to easily manage their data requests and access credentials. The data access portal facilitates the creation and internal organization of the data access committees as well as the linkage of data usage conditions to specific datasets. The interface includes filters for browsing requests and page to visualize the request history helping with the handling of data access requests. EUCANCan: toward a federation of clinical institutions in oncology The EUropean-CAnadian CANcer Network worked towards building a federated network to advance personalized medicine in oncology, by promoting the standard analysis, management and sharing of harmonized genomic and phenotypic data. The EGA led tasks on defining data flows and preparing an adapted infrastructure for long-term data storage and sharing. One of the key contributions was the conception of the EGA communities, offering standard and interoperable solutions for data discovery, processing, and sharing to projects and institutions that would like to manage and share data in the context of the EGA ecosystem. What's Next? The participation in projects such as CINECA, EUCANCan, and euCanSHare provide us with experience for future projects. We are happy to enhance data sharing and reuse, vital for advancing clinical and genomic research. The Discovery Portal is a wonderful proof of concept for the Beacon network. Next, we will finalise both the network and the user interface, and make sure it can be applied to more clinically-centred settings like hospitals. Most data hosted at the EGA are about cancer research. Currently, we contribute to building tools and infrastructure to empower oncology research in several European projects such as EUCAIM, EUCANIMAGE and EOSC4Cancer. We also do not lose sight of initiatives in the field such as the International Cancer Genome Consortium (ICGC) with the project ARGO, whose data model was adopted in EUCanCan.

  Blog cineca-eucancan-and-eucanshare-were-concluded-in-june

• The EGA at the International Congress of Human Genetics

  Today is the start of the International Congress of Human Genetics (ICHG). This event, hosted by the African Society of Human Genetics (AfSHG) and the Southern African Society for Human Genetics (SASHG), will reunite international experts to highlight how genomic technologies are being managed to address challenges generated by the current status of Human Health and Genomics. The European Genome-phenome Archive (EGA) will be at the Congress participating in workshops, meetings and talks where topics such as data access and discovery as well as the Federated EGA will be present. Data access and discovery In the context of the “Federated data analysis workshop“ that will be held the 26ᵗʰ, managed in the context of the CINECA project, a hands-on-session on Beacon v2 Discovery will be led by Mauricio Moldes. Another session on authorisation and data access will be presented by Mallory Freeberg and Coline Thomas, with and introduction by Thomas Keane. During the workshop, an end-to-end federated data analysis use case will be presented. Data access and discovery In the context of the “ Federated data analysis workshop“ that will be held the 26ᵗʰ, managed in the context of the CINECA project, a hands-on-session on Beacon v2 Discovery will be led by Mauricio Moldes. Another session on authorisation and data access will be presented by Mallory Freeberg and Coline Thomas, with and introduction by Thomas Keane. During the workshop, an end-to-end federated data analysis use case will be presented. During the last four years, CINECA has been identifying gaps in data sharing between Africa, Canada and Europe in order to build a federated solution for data access. Thomas Keane will present the project within the sessions happening the 24ᵗʰ. The Federated EGA at the ICHG A Federated EGA poster will be shown during the Poster Session 1 that will take place the 23ʳᵈ. The objective is to bring awareness of the European Genome-phenome Archive as a resource for permanent archive and secure data sharing. In this context, the network generated by the Federated EGA is key for cases where research data cannot be shared outside local jurisdictions. The Federated EGA was officially launched on 2022 with research institutes from five countries becoming the first nodes of this network. Nowadays, with more than 20 nodes preparing to join, it aims to become the largest human omics data sharing initiative towards understanding human health and disease. The H3Africa Initiative and the African research represented in the EGA 1.1% of the EGA studies include samples from African populations. Countries such as South Africa, Kenya, Uganda or Egypt, among others, are present in the 72.577 samples from African individuals archived at the EGA. 23 EGA datasets are managed by the Human Heredity and Health in Africa Initiative (H3Africa). This Initiative will celebrate its Consortium Meeting the 27ᵗʰ and 28ᵗʰ, back-to-back with the ICHG. H3ABioNet, the Pan African Bioinformatics Network for the H3Africa consortium, will also take this context to celebrate its 10-Year Symposium during the Congress. Members of the EGA team will attend both of them, as the H3ABioNet works in conjunction with H3Africa projects, to submit data to the European Genome-Phenome Archive.

  Blog the-ega-at-the-international-congress-of-human-genetics

• Shedding light over COVID-19 susceptibility and severity

  “One of the most remarkable features of SARS-CoV-2 infection is the variation in consequence ranging from asymptomatic to life-threatening” state the authors of the majestic Nature paper released in accelerated pre-view on July 2021. This variation in consequences represent not only an issue of burning medical relevance, but also a scientific and intellectual challenge for scientists around the globe. Researchers are known to be easily triggered by a challenge, and they recently demonstrated to be even better at double their efforts to focus on an urgent societal need. In this work led and coordinated by the COVID-19 Host Genetics Initiative (COVID-19 HGI), researchers gathered data from 49,562 cases and two million controls from 46 studies performed worldwide. The majority of the data has been deposited at the EGA, where 29 datasets have been collected under the study number EGAS00001005304. Data gathered from diverse sources conferred a huge robustness to the results. Genetic data from different ancestry origin were included in the analyses, even though data from patients with European origin was highly predominant (approx. 75%). Separated analysis of the different ancestries gave rise to relevant differences in the results, highlighting how important it is to take this aspect in consideration for future studies. Data from the individual studies was compiled into three categories according to COVID-19 severity for a meta-analysis: (a) critically ill cases (b) moderate or severe cases (c) all cases. They were paired with non-COVID-19-reported controls. All three analysis resulted in a total of 13 genetic loci associated with COVID-19 severity. Out of those, 9 loci associated specifically with critical illness, while 6 (a few overlapped) associated with moderated illness. Some genomic position matched previous findings. Interestingly, working with such an enormous amount of data allowed the depth to discriminate association with disease susceptibility vs severity, an issue of large medical relevance. Several loci mapped into biological relevant genes, like TYK2, PPP1R15A and FOXP4, previously implicated in immune response and/or lung functions. Researchers participating in the COVID-19 Host Genetics Initiative have worked in an unprecedented time-tight collaboration, prioritizing data sharing and collective results to tackle the pandemic affecting the world. The scientific community won’t miss any of the lessons to learn from this, and the EGA is ready to keep working to enable safe data sharing and fruitful collaborations.

  Blog covid-19-susceptibility-and-severity