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• Translating Gene-Calcium Interactions to Precision Medicine for Colorectal Cancer

  Identify functional and rare SNPs and their interactions with Ca intake levels in relation to risk of incident adenoma using whole-exome resequencing of 2468 colorectal adenoma cases and controls from PLCO. We will genotype promising rare and functional SNPs associated with incident adenoma in 570 incident cancer cases, 1,710 healthy controls, 710 adenoma recurrence cases and 966 recurrent adenoma controls from the intervention arm of PLCO to both confirm the associations with adenoma, and to identify when, in the natural history of CRC, chemoprevention by Ca-gene interactions occurs. We hypothesize that Ca-gene interactions prevent early-stage (incident adenoma) and mid-stage (adenoma recurrence) carcinogenesis as well as span the entire CRC carcinogenesis spectrum (i.e. incident CRC).

  Study phs002164

• Solve RD data - Short-Read Whole-Genome Sequencing, raw data, tuh-kounap_group samples

  Solve-RD SR-WGS data generated for 3 samples provided by the group tuh-kounap

  Dataset EGAD00001015514

• Inferring causal genes at type 2 diabetes GWAS loci through chromosome interactions in islet cells

  Resolving causal genes for type 2 diabetes at loci implicated by genome-wide association studies (GWAS) requires integrating functional genomic data from relevant cell types. Chromatin features in endocrine cells of the pancreatic islet are particularly informative and recent studies leveraging chromosome conformation capture (3C) with Hi-C based methods have elucidated regulatory mechanisms in human islets. However, these genome-wide approaches are less sensitive and afford lower resolution than methods that target specific loci. Methods: To gauge the extent to which targeted 3C further resolves chromatin-mediated regulatory mechanisms at GWAS loci, we generated interaction profiles at 23 loci using next-generation (NG) capture-C in a human beta cell model (EndoC-βH1) and contrasted these maps with Hi-C maps in EndoC-βH1 cells and human islets and a promoter capture Hi-C map in human islets. Results: We found improvements in assay sensitivity of up to 33-fold and resolved ~3.6X more chromatin interactions. At a subset of 18 loci with 25 co-localised GWAS and eQTL signals, NG Capture-C interactions implicated effector transcripts at five additional genetic signals relative to promoter capture Hi-C through physical contact with gene promoters. Conclusions: High resolution chromatin interaction profiles at selectively targeted loci can complement genome- and promoter-wide maps.

  Dataset EGAD50000000517

• Development of humanized mice for human hematopoisis and immunity research

  We obtained peripheral blood or bone marrow samples from 27 FLT3-ITD+ acute myeloid leukemia (AML) patients and created humanized mice engrafted with human AML cells. We sequenced DNA obtained from patient-derived pre-leukemia and leukemia cells and engrafted human hematopoietic cells and leukemia cells en bulk to detect AML-associated mutations and determine mutations contributing to in vivo. From five of these patients, we also performed single cell DNA sequencing to determine clonal heterogeneity and mutational complexity of human pre-leukemic and leukemic cells and to discriminate between permissive and leukemogenic mutations. Finally, inhibition of a leukemogenic mutation led to effective elimination of human AML cells in vivo, and a co-administration of an inhibitor of anti-apoptotic pathway further improved killing of AML cells in vivo.

  Study JGAS000122

• NuGen Targeted Sequencing of 574 DLBCL Cases of Non-China Cohort from Phoenix Clinical Trial

  NuGen 99-Gene-Panel Targeted Sequencing of 574 DLBCL Cases of Non-China Cohort from Phoenix Clinical Trial. Check the Associated Publication for More Experimental Details.

  Dataset EGAD00001008132

• XClone for analyzing somatic copy number alterations

  Somatic copy number alterations (CNAs) are major mutations that contribute to the development and progression of various cancers. Despite a few computational methods proposed to detect CNAs from single-cell transcriptomic data, the technical sparsity of such data makes it challenging to identify allele-specific CNAs, particularly in complex clonal structures. In this study, we present a statistical method, XClone, that strengthens the signals of read depth and allelic imbalance by effective smoothing on cell neighborhood and gene coordinate graphs to detect haplotype-aware CNAs from scRNA-seq data. By applying XClone to multiple datasets with challenging compositions, we demonstrated its ability to robustly detect different types of allele-specific CNAs and potentially indicate whole genome duplication, therefore enabling the discovery of corresponding subclones and the dissection of their phenotypic impacts.

  Study EGAS00001007854

• WGS dataset for Genomic rearrangements in Pediatric Cancer

  Dataset EGAD00001008272

• sWGS of core biopsies from localized breast cancer patients

  Paired end shallow whole genome sequencing (sWGS) data for the identification of genomewide somatic copy number alterations (SCNA) and the estimation of tumor fractions.

  Dataset EGAD00001008397

• cfDNA and CDX/PDX methylation profiling in Small Cell Lung Cancer

  This study contains methyl-binding domain sequencing and shallow whole genome sequencing from circulating free DNA (cfDNA) for 79 patients with small cell lung cancer (SCLC) and 78 non-cancer controls. We also sequence genomic DNA (both methyl-binding domain sequencing and shallow whole genome sequencing) from 30 circulating-tumour-cell derived explant models (CDXs, from 23 unique patients with SCLC), 20 patient derived explant models (PDXs, from 10 unique patients with SCLC) and 13 lung tissue samples.

  Dataset EGAD00001008673

• Genomic analysis for intrahepatic cholangiocarcinoma

  Intrahepatic cholangiocarcinomas (iCCs) are characterized by their rarity, difficulty in diagnosis, and overall poor prognosis. We performed comprehensive genomic characterization of treatment-naive iCC. This study reports a large-scale genomic analysis of iCC. The findings could assist in patient stratification with iCCs and in developing rational therapeutic strategies.

  Dataset EGAD00001008557

• CHILD Study Dataset

  This data set contains the CRAM files for the samples in the CHILD cohort, sequenced on the Illumina HiSeq X platform.

  Dataset EGAD00001009710

• Aberrant RNA-splicing (neojunctions) offers a new source for targets, and our neoantigen discovery platform (SNIPP) characterizes a novel class of clonally-expressed splicing-derived neoantigens that elicit a CD8+ T-cell-mediated tumor killing response.

  RESULTS: Our pipeline identified 789 public neojunctions, with 32 neojunctions concurrently identified in transcriptomic and proteomic glioma data and predicted to be presented by HLA-A*02:01 with high confidence. IVS and subsequent 10x VDJ scRNA-seq identified TCR clonotypes reactive against neojunctions in RPL22 (n=7) and GNAS (n=1), the latter being highly intratumorally-conserved (detected in > 90% of spatially-mapped biopsies across 17/56 patients (26.78%)). TCR-transduced T-cells demonstrated recognition and immunogenic activation against endogenously processed and presented neoantigens in multiple GBM PDX cell lines. Furthermore, IDH1-mutant oligodendroglioma samples demonstrated significantly elevated expression of neojunctions over IDH1-mutant astrocytoma and IDH1wt subtypes. Differential gene expression (DESeq2) identified decreased expression of splicing factors due to oligodendroglioma-specific co-deletion of Chromosomes 1p/19q. siRNA knockdown of these splicing factors (e.g. SF3A3, SNRPD2) in IDH1wt glioma cells resulted in significantly increased expression of corresponding neojunctions.

  Study EGAS00001007986

• T cell receptor repertoire in cell-free DNA as a proxy for tumor infiltrates in patients treated with pembrolizumab

  Profiling tumour and systemic T-cell receptor (TCR) repertoires can identify features associated with clinical benefit of cancer patients on immune checkpoint blockade therapy. This study reports on diversity and specificity analysis of TCR sequences from 59 tumor, 306 peripheral blood (PBMC), and 73 cell-free DNA (cfDNA) samples from 81 patients with solid tumors treated with pembrolizumab. This analysis reveals that head and neck carcinomas have significantly lower PBMC diversity and shorter persistence of pembrolizumab-induced diversification compared to other cancers. Using GLIPHII (Grouping Lymphocyte Interactions with Paratope Hotspots), we find that tumor-derived clonotypes form non-microbial specificity signatures that are shared across patients and cancer types. Tumor-derived clonotypes are enriched in cfDNA compared to PBMCs, despite the diversity of cfDNA TCR repertories being two orders of magnitude lower than PBMCs. TCRs shared between tumors and cfDNAs persist in PBMCs beyond 50 weeks of treatment, suggesting cfDNA captures clonotypes contributing to anti-tumor immune surveillance.

  Study EGAS50000001306

• Single-cell RNA-seq and spatial transcriptomics data for the sarcoidosis baseline project

  Granulomas are lumps of immune cells that can form in various organs. Most granulomas appear unstructured, yet they have some resemblance to lymphoid organ formation. To better understand granuloma formation, we performed single-cell sequencing and spatial transcriptomics on granulomas from patients with sarcoidosis and bioinformatically reconstructed the underlying gene-regulatory networks. We discovered an immune stimulatory environment in granulomas that repurposed transcriptional programs associated with lymphoid organ development. Granuloma formation followed characteristic spatial patterns and involved genes linked to immunometabolism, cytokine and chemokine signaling, and extracellular matrix remodeling. Three cell types emerged as key players in granuloma formation: metabolically reprogrammed macrophages, cytokine-producing Th17.1 cells, and fibroblasts with inflammatory and tissue remodeling phenotypes. Pharmacological inhibition of one of the identified processes attenuated granuloma formation in a sarcoidosis mouse model. We show that human granulomas adopt characteristic aspects of normal lymphoid organ development in aberrant combinations, indicating that granulomas constitute aberrant lymphoid organs.

  Study EGAS00001006970

• ANGIOPREDICT - an FP7-funded project enabling personalised medicine for patients with metastatic colorectal cancer.

  Exome (*_{N,T}{1,2}) RNAseq (polyA - *_PolyA, and RiboZero - *_RibZ) Methylation (SeqCapEpi - MAPD*).

  Dataset EGAD00001008463

• Solve-RD_EuroNMD_cohort-1_DF1+2_V1

  Solve-RD data submitted to the ERN-EuroNMD cohort for re-analysis (Data freeze 1+2) v1

  Dataset EGAD00001009768

• Development of a fully human glioblastoma-in-brain-spheroid model for accelerated translational research

  In glioblastoma (GBM) the intricate interplay between tumor cells and the surrounding microenvironment plays a crucial role in tumor progression, invasion, and therapeutic resistance. So far, studying these interactions in a controlled and representative model system has been challenging. Here, we report the development of hGliCS, a human glioma-cortical spheroid model that allows the elucidation of the biology of GBM cells and their interactions with a human-specific brain-like microenvironment and neurons. GBM cells efficiently invade the cortical spheroids, forming a well-connected network of communicating cells. The heterogeneous cellular states of the GBM cells within this model closely resembled findings previously observed in glioblastoma patients and in mouse xenografts. We observed a transition from predominantly mesenchymal-like cells to heterotopic states with a high diversity. In contrast to the substantial changes observed in the tumor cell population, the impact of the GBM cells on the neurons was minimal. We further demonstrate the suitability of hGliCS to test compounds targeting tumor-specific neurobiological features.

  Study EGAS50000000757

• cell-free DNA Whole Genome Sequencing of 3784 samples on MGI and Illumina platform

  The dataset of Integrative modeling of tumor genomes and epigenomes for enhanced cancer diagnosis by cell-free DNA includes 3784 whole genome sequencing bam files on the MGI and Illumina platform. The analyzed samples include plasma samples from normal individuals and patients with cancer.

  Dataset EGAD00001009335

• Nanobody-Tethered Transposition Allows for Multifactorial Chromatin Profiling at Single-Cell Resolution

  Chromatin states are functionally defined by a complex combination of histone modifications, transcription factor binding, DNA accessibility, and other factors. However, most current single-cell-resolution methods are unable to measure more than one aspect of chromatin state in a single experiment, limiting our ability to accurately measure chromatin states. Here we introduce nanobody-tethered transposition followed by sequencing (NTT-seq), a new assay capable of measuring the genome-wide presence of multiple histone modifications and protein-DNA binding sites at single-cell resolution. NTT-seq utilizes recombinant Tn5 transposase fused to a set of secondary nanobodies (nb). Each nb-Tn5 fusion protein specifically binds to different immunoglobulin-G antibodies, enabling a mixture of primary antibodies binding different epitopes to be used in a single experiment. We apply bulk- and single-cell NTT-seq to generate high-resolution multimodal maps of chromatin states in cell culture and cells of the human immune system, demonstrating the high accuracy and sensitivity of the method. We further extend NTT-seq to enable simultaneous profiling of cell-surface protein expression alongside multimodal chromatin states to study cells of the immune system.

  Study phs003068

• RNA-Seq of 584 DLBCL Cases of Non-China Cohort from Phoenix Clinical Trial

  Standard RNA-Seq datasets. Check the associated paper for more details.

  Dataset EGAD00001008131

• BC Cancer, part of the Provincial Health Services Authority, Technology Development Office, Data Access Committee (PHSA TDO DAC)

  Access to data generated by BCCA is made available by completing the data access agreement for review by the data access committee and will be granted to qualified investigators for appropriate use.

  Dac EGAC00000000011

• NPC genome-wide human SNP array data

  nasopharyngeal carcinoma genome-wide human SNP array data for 4083 NPC cases and 4811 controls

  Dataset EGAD00010002296

• The Dutch Microbiome Project Batch 1

  The Dutch Microbiome Project (DMP) data includes shotgun metagenomic sequencing of faecal samples 8,208 Dutch individuals. Paired-end sequencing was performed using Illumina HiSeq 2000 platform. Data is archived in two batches to facilitate easier data access and upload to EGA. Batch 1 of DMP includes 4396 samples.

  Dataset EGAD00001007027

• RNAseq data for Failure of Differentiation of the Rhombic Lip Constitutes Medulloblastoma

  We used single-cell transcriptomics to study cells from the developing human cerebellum, and show that different molecular subgroups of medulloblastoma resemble distinct glutamatergic progenitors.

  Dataset EGAD00001008458

• Irish Covid19 WGS Alignment Data

  Dataset contains 483 Irish origin Individuals with Covid19. For WGS, Alignment has been done using BWA-mem (sention v 201808.03 ) and BAM file generated.

  Dataset EGAD00001010098

• LBC1936 fastq files

  1075 members of the LBC1936 were sequenced using the Illumina HiSeq X platform. This dataset contains the paired fastq files.

  Dataset EGAD00001008774

• GCAT| WGS FASTQ V1

  This dataset include FASTQ files of 808 samples from GCAT cohort. Technology used HiSeq 4000, read length 150 bp, inner mate distance 300 bp. For each sample the paired -ends are generated in separated files. Each FASTQ is splitted in multiple LANEs and grouped by the Multiplex index.

  Dataset EGAD00001008201

• Solve-RD_RND_cohort-1_DF1+2_V1

  Solve-RD data submitted to the ERN-RND cohort for re-analysis (Data freeze 1+2) v1

  Dataset EGAD00001009769

• Ancient Yakuts genomes and metagenomes

  Read data and bam alignments for 124 ancient yakuts

  Dataset EGAD50000001903

• Solve-RD_ITHACA_cohort-1_DF1+2_V1

  Solve-RD data submitted to the ERN-ITHACA cohort for re-analysis (Data freeze 1+2) v1

  Dataset EGAD00001009770

• Irish Covid19 RNASeq Alignment Data files

  The Dataset contains 446 Covid19 patient's RNASeq Alignment files in BAM format for both genomic and transcriptomic alignment.

  Dataset EGAD00001010099

• Irish Covid19 WGS Raw Reads

  Dataset contains 483 Irish origin Individuals with Covid19. paired end sequencing has been performed For WGS and later processed by using sention v 201808.03.

  Dataset EGAD00001010186

• WGS samples for study EGAS00001001623

  Dataset EGAD00001001856

• Solve-RD multi-omics data chud-faivre cohort

  The dataset includes short-read whole-genome sequencing (SR-WGS) data, SR-RNAseq data, OGM (Bionano) data, LR-WGS data, Epigenetics (RBSS) data and deep-WES data generated within the project Solve-RD from biosamples submitted by the group chud-faivre. The cohorts consists of 111 individuals recruited as part of Solve-RD cohorts 2-4 and aligns with ERN-ITHACA related disease entities (for a description of the Solve-RD cohorts see www.solve-rd.eu/fact-sheet-solve-rd-cohorts).

  Dataset EGAD00001015811