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• RNAseq for 8 PDX

  RNAseq for #111, #1177, #206, #201, #29, #931, WO-19, WO-2

  Dataset EGAD50000000116

• DATA FILES FOR PCGP MB WGS - Supersedes (EGAD00001000269)

  DATA FILES FOR PCGP MB WGS - Supersedes (EGAD00001000269)

  Dataset EGAD00001001864

• Linked-reads for Juvenile Pilocytic Astrocytomas

  Matched tumor-normal data for 6 JPAs. Generated using 10X Genomics Linked-reads

  Dataset EGAD00001011114

• Collaborative Cohort of Cohorts for COVID-19 Research (C4R): Framingham Heart Study (FHS)

  Cohort DescriptionIn 1948, the researchers recruited 5,209 men and women between the ages of 30 and 62 from the town of Framingham, Massachusetts, and began the first round of extensive physical examinations and lifestyle interviews that they would later analyze for common patterns related to CVD development. Since 1948, the subjects have returned to the study every two years for an examination consisting of a detailed medical history, physical examination, and laboratory tests, and in 1971, the study enrolled a second-generation cohort -- 5,124 of the original participants' adult children and their spouses -- to participate in similar examinations. The second examination of the Offspring cohort occurred eight years after the first examination, and subsequent examinations have occurred approximately every four years thereafter. In 1994, the need to establish a new study reflecting a more diverse community of Framingham was recognized, and the first Omni cohort of the Framingham Heart Study, consisting of 506 participants, was enrolled. In April 2002 4095 third generation of participants, the grandchildren of the original cohort, were added. In 2003, 103 spouses of the offspring Cohort (NOS), and a second group of 410 Omni participants were enrolled. Through 2019, the original cohort has completed a total of 32 exams, the Offspring cohort 9 exams, the OMNI1 cohort 4 exams, and GEN3, NOS and OMNI2 cohorts each have completed 3 exams. The FHS is a joint project of the National Heart, Lung and Blood Institute and Boston University.Data Being Submitted Wave 1 questionnaire data includes 3967 variables for up to 3112 FHS participants in C4R.Wave 2 questionnaire data includes 448 variables for up to 2337 FHS participants in C4R.Dried Blood Spot/Serosurvey data includes 7 variables for up to 2189 FHS participants in C4R.Derived data includes 43 variables for up to 3151 FHS participants in C4R.Phenotype data includes 113 variables for up to 3151 FHS participants in C4R.

  Study phs002911

• 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

• Short and long-read genome sequencing methodologies for somatic variant detection; genomic analysis of a patient with diffuse large B-cell lymphoma

  Recent advances in throughput and accuracy mean that the Oxford Nanopore Technologies (ONT) PromethION platform is a now a viable solution for WGS. New bioinformatic methods have been developed to take advantage of this long read data, however much of the validation of these tools has focussed on calling germline variants (both SNVs and structural variants). Somatic variants are outnumbered many-fold by germline variants and their detection is further complicated due to their frequency varying depending on tumour purity/subclonality. Here, we evaluate the extent to which Nanopore WGS enables genome-wide detection and analysis of somatic variation. We do this through sequencing tumour and germline genomes for a patient with diffuse B-cell lymphoma. We examine the capability of currently available tools for calling somatic variants in ONT data by comparing the data with results from 150bp short-read sequencing of the same samples. We then conduct a detailed analysis of the performance of multiple long-read mappers and structural variant callers for calling large, somatic structural variants (SVs) in ONT data. Our protocol achieved yields of up to 96 mapped Gb per PromethION flow cell with average read lengths of ~5kb. Calling germline SNVs from these data achieved good specificity and sensitivity. However, results of somatic SNV calling highlight the need for the development of specialized joint calling algorithms. Our analysis of structural variants shows that the comparative performance of different tools varies significantly between SV types, and suggest long reads are especially advantageous for calling large somatic deletions and duplications. Finally, we highlight the utility of long reads for phasing clinically relevant variants by using the ONT data to confirm that a somatic 1.6Mb deletion and a p.(Arg249Met) mutation involving TP53 are oriented in trans.

  Study EGAS00001004266

• Somatic copy number alteration and fragmentation analysis in circulating tumor DNA for cancer screening and treatment monitoring in colorectal cancer patients

  Background: Analysis of circulating free DNA (cfDNA) is a promising tool for personalized management of colorectal cancer (CRC) patients. Untargeted cfDNA analysis using whole-genome sequencing (WGS) does not need a priori knowledge of the patient´s mutation profile. Methods: Here we established LIquid biopsy Fragmentation, Epigenetic signature and Copy Number Alteration analysis (LIFE-CNA) using WGS with ~6x coverage for detection of circulating tumor DNA (ctDNA) in CRC patients as a marker for CRC detection and monitoring. Results: We describe the analytical validity and a clinical proof-of-concept of LIFE-CNA using a total of 259 plasma samples collected from 50 patients with stage I-IV CRC and 61 healthy controls. To reliably distinguish CRC patients from healthy controls, we determined cutoffs for the detection of ctDNA based on global and regional cfDNA fragmentation patterns, transcriptionally active chromatin sites, and SCNAs. We further combined global and regional fragmentation pattern into a machine learning classifier to accurately predict ctDNA for cancer detection. By following individual patients throughout their course of disease, we show that LIFE-CNA enables the reliable prediction of response or resistance to treatment up to 3.5 months before commonly used CEA. Conclusion: In summary, we developed and validated a sensitive and cost-effective method for untargeted ctDNA detection at diagnosis as well as for treatment monitoring of all CRC patients based on genetic as well as non-genetic tumor-specific cfDNA features. Thus, once sensitivity and specificity have been externally validated, LIFE-CNA has the potential to be implemented into clinical practice. To the best of our knowledge, this is the first study to consider multiple genetic and non-genetic cfDNA features in combination with ML classifiers and to evaluate their potential in both cancer detection and treatment monitoring.

  Study EGAS00001006490

• Exceptional Outcomes in a Phase Ib Study Combining PARP and MEK Inhibition, With or Without Anti-PD-L1, for BRCA-Wildtype Platinum-Sensitive Recurrent Ovarian Cancer

  To evaluate regimens combining PARP and MEK inhibition, with or without PD-L1 inhibition, for BRCA-wildtype platinum-sensitive recurrent ovarian cancer (PSROC).

  Study EGAS00001007496

• PDAC Phenotype and Germline Genotype Data Access Committee

  This Data Access Committee (DAC) is responsible for reviewing and approving requests for access to controlled phenotype metadata and derived germline FUT2/FUT3 genotype data from patients with pancreatic ductal adenocarcinoma (PDAC). Access is granted to bona fide researchers for non-commercial research purposes only, subject to approval by the DAC and in accordance with the original informed consent and applicable ethical regulations.

  Dac EGAC50000000893

• Genomic determination for Homologous Recombination Deficiency (HRD) by shallow Whole Genome Sequencing (sWGS)

  Genomic determination for Homologous Recombination Deficiency (HRD) by shallow Whole Genome Sequencing (sWGS) with shallowHRD (PMID : 32315385) on 55 triple-negative breast cancer Patient Derived-Xenograft (PDX) treated with platinum.

  Study EGAS00001005926