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• Development of hunanized mice for human hematopoisis and immunity research

  We obtained peripheral blood or bone marrow samples from 112 acute myeloid leukemia patients and examined sensitivity and resistance of the AML samples to molecular targeting drugs. By doing RNA sequencing using AML cells, we found heterogenous gene expression patterns in AML with different mutational landscapes. From the RNA sequencing, we identified anti-apoptosis, cell cycle progression, and immune-related signals as pathways up-regulated in AML cells as compared with normal CD34+ cells. From the pathway analyses, we further setup in vitro experiments to find vulnerability genes in clinically-aggressive AML. BIRC, BCL2, MCL1, AURKB, and KIF10 may be essential molecules for AML cell survival and proliferation.

  Study JGAS000253

• Bulk and RIP-seq transcriptome datasets from skin fibroblasts in PTBP1- and PTBP2-related disorders

  PTBP1- and PTBP2-related disorders are rare human conditions that cause variable neurodevelopmental phenotypes, including intellectual disability and behavioral problems such as autism spectrum disorder, anxiety, aggressiveness, and attention disorders, with or without hyperactivity. PTBP1-related disorder is also associated with skeletal dysplasia. In this study, we generated bulk RNA sequencing and RNA immunoprecipitation sequencing (RIP-seq) data from skin fibroblasts obtained from patients and healthy controls.

  Study EGAS50000001210

• miRNA

  miRNA Sequencing of olfactory mucosa (OM) cells derived from cognitively healthy and individuals with AD exposed to traffic-related ultrafine particles (UFPs) for 72h in submerged cultures. The UFPs used for exposures were: A0 and A20. Exposures were compared to the corresponding blank samples.

  Dataset EGAD50000001532

• Glioblastoma stem cell lines WGS data

  WGS data for 20 Glioblastoma stem cell (GSC) lines and matched blood samples. Fastq files are available. For 10 GSC samples and the 10 matched blood samples the reads are on 3 fastq files per sample

  Dataset EGAD00001006488

• A living biobank of breast cancer organoids captures disease heterogeneity

  Breast Cancer (BC) comprises multiple distinct subtypes that differ genetically, pathologically, and clinically. Xeno-transplantation and direct culturing of tumor tissue are increasingly used in drug development and personalized medicine strategies. Here, we describe a robust protocol for long-term culturing of human mammary epithelial organoids. Using this protocol, 101 BC organoid lines were generated, broadly recapitulating the diversity of the disease. BC organoid morphologies typically matched the histopathology, hormone receptor-, and HER2 status of the original tumor. DNA copy number variations as well as sequence changes were consistent within tumor-organoid pairs and largely retained even after extended passaging. BC organoids furthermore populated all major gene expression-based classification groups and allowed drug screens in vitro and upon xenotransplantation. This study describes a representative collection of well-characterized BC organoids available for cancer research and drug development, as well as a strategy to assess in vitro drug response in a personalized fashion.

  Study EGAS00001002158

• OLINK metadata EGA v2

  Sample metadata for the olink dataset. This dataset includes subject-level data and longitudinal visit day information for the corresponding samples.

  Dataset EGAD00001011165

• single nuclei multiomics (ATAC-RNA) of KOLF2.1J human induced pluripotent stem cells-derived differentiated dopaminergic neurons

  We processed nuclei from hIPSCs differentiated optimized protocols for generating dopaminergic neurons. Cells differentiated with a first iteration were RNA and ATAC-sequenced, to understand our protocol caveats to address for optimization. Cells differentiated with a second protocol and in vivo were RNA-sequenced to validate the identities of our cells.

  Study EGAS50000001418

• Molecular and phenotypic data for patients enrolled in the IMmotion150 trial

  Tumor transcriptome and whole exome sequencing data (matched tumor/normal for somatic mutation calling) along with key phenotypic information are provided for patients enrolled in the phase 2 IMmotion150 trial, assessing efficacy of atezolizumab monotherapy or combination of atezolizumab and bevacizumab versus standard of care (sunitinib) in 1L renal cell carcinoma. This data set accompanies the respective Nature Medicine publication (PMID: 29867230).

  Dataset EGAD00001004183

• Identification of responsible genes and development of standardized medicine for familial breast cancer by genetic analysis with NGS technology

  Aims: To clarify risk of germline variants of known causal genes for Hereditary Breast Ovarian Cancer Syndrome in Japan by combinatorial analysis of somatic and germline variants in the breast cancer tissue. Methods: Target caputure analysis by using Illumina HiSeq 2000; the panel genes are 119 genes including 30 HBOC known causal genes. Participants/Materials: 108 whole blood and 124 primary tumor samples from familial breast cancer patients.

  Study JGAS000224

• Chromatin_accessability_in_cytokine_induced_immune_cell_states

  We isolated T cells and monocotyes from healthy platelet donors and cultured them in resting and stimulated conditions with addition of a range of cytokines. We performed K27Ac ChM sequencing to assess the chromatin activity in different cytokines treated cells. These cellular profiles were used to map risk variants to the cytokine-induced cell states relevant for autoimmune diseases.

  Study EGAS00001002749

• Chromatin_accessability_in_cytokine_induced_immune_cell_states

  We isolated T cells and monocotyes from healthy platelet donors and cultured them in resting and stimulated conditions with addition of a range of cytokines. We performed ATAC sequencing to assess the chromatin accessability in different cytokines treated cells. These cellular profiles were used to map risk variants to the cytokine-induced cell states relevant for autoimmune diseases.

  Study EGAS00001003501

• Elucidating the heterogeneity of immunotherapy response and immune-related toxicities by longitudinal ctDNA and immune cell compartment tracking in lung cancer

  The dataset for the study Elucidating the heterogeneity of immunotherapy response and immune-related toxicities by longitudinal ctDNA and immune cell compartment tracking in lung cancer includes 207 bam files from hybrid capture targeted error-correction next-generation sequencing (TEC-Seq) from plasma cell-free DNA and matched white blood cell DNA from 30 individuals with non-small cell lung cancer, alongside 46 bam files from whole exome sequencing of tumor and matched normal DNA for 21 individuals with non-small cell lung cancer who received immunotherapy-containing regimens.

  Dataset EGAD00001011991

• METABRIC

  The elucidation of breast cancer subgroups and their molecular drivers requires integrated views of the genome and transcriptome from representative numbers of patients. We present an integrated analysis of copy number and gene expression in a discovery and validation set of 997 and 995 primary breast tumours, respectively, with long-term clinical follow-up. Inherited variants (CNVs, SNPs) and acquired somatic copy number aberrations (CNAs) were associated with expression in 40% of genes, although the landscape was dominated by cis and trans-acting CNAs. By delineating expression outlier genes driven in cis by CNAs, we identified putative cancer genes, including deletions in PPP2R2A, MTAP, and MAP2K4. Unsupervised analysis of paired DNA/RNA profiles revealed novel subgroups with distinct clinical outcomes, which reproduced in the validation cohort. These include a high-risk, ER-positive 11q13/14 cis-acting subgroup and a favourable prognosis subgroup devoid of CNAs. Trans-acting aberration 0152hotspots were found to modulate subgroup-specific gene networks, including a TCR deletion-mediated adaptive immune response in the 0152CNA-devoid sub-group and a Basal-specific chromosome 5 deletion-driven mitotic network. Our results provide a novel molecular stratification of the breast cancer population, derived from the impact of somatic copy number aberrations on the transcriptome.

  Study EGAS00000000083

• Genome-wide genotype data for 1,433 ni-Vanuatu

  Here, we generated genome-wide genotype data for 1,433 contemporary ni-Vanuatu and assessed their fine-scale genetic structure, in order to address central questions about the settlement of western Remote Oceania.

  Study EGAS00001005910

• 108 WGS of epileptic patients from the CENet cohort

  Dataset is described in doi: https://doi.org/10.1101/2022.12.13.22283363

  Dataset EGAD00001011301

• WES and Panel-seq data of pediatric tumors

  Paired-end WES and targeted Panel-seq data from 140 pediatric tumor samples. Sequencing was performed on Illumina HiSeq 4000, MiSeq or HiSeq 2500.

  Dataset EGAD50000000577

• 18 ctDNA and matched tumor sequencing from SCLC patients

  BAM files corresponding to sequencing of 18 circulating tumor DNA and matched tumor samples from SCLC patients. Each ctDNA sample was sequenced twice.

  Dataset EGAD00001005460

• 28 ctDNA and matched tumor sequencing from SCC patients

  BAM files corresponding to sequencing of 28 circulating tumor DNA and matched tumor samples from SCC patients. Each ctDNA sample was sequenced twice.

  Dataset EGAD00001005462

• Sequencing of paediatric High Grade Gliomas and DIPG

  Paediatric high grade glioma (pHGG) and diffuse intrinsic pontine glioma (DIPG) are a phenotypically diverse collection of tumours which molecular profiling studies have refined into age- and location-based subgroups driven by unique genetic and epigenetic alterations. Despite this, the rarity of these tumours means individual studies are underpowered to investigate subgroup-specific changes and to identify low frequency events recurrently targeting specific pathways. We have collated genomic data from 143 unpublished cases up to 30 years of age along with those from 18 previously published datasets in an integrated analysis comprising 1067 unique patients across all anatomical compartments of the CNS, with histone mutation status available for 893 cases (n=67 H3.3G34R/V, n=316 H3.3K27M, n=68 H3.1/H3.2K27M). Distinct clinicopathological and molecular subgroups are defined by these histone mutations, with several novel co-segregating mutations identified through these aggregated analyses, including loss of FBXW7 in H3.3G34R/V, TOP3A rearrangements in H3.3K27M, and BCOR mutations in H3.1K27M. Histone wild-type subgroups can be further refined by the presence of key oncogenic events (PDGFRA or EGFR amplification/mutations) or methylation profiles which molecularly more closely resemble pleomorphic xanthoastrocytoma or other low grade gliomas. The burden of genomic aberrations decreases with age, highlighting the infant population as biologically and clinically distinct. Across the whole cohort, we identify novel previously unrecognised pathway dysregulation in small subsets of tumours (e.g. splicing, WNT, immune response) which make up the umbrella classification of paediatric diffusely infiltrating gliomas. The integrated dataset helps to further define the molecular diversity of the disease, opening up novel avenues for biological study and providing a basis for functionally defined future treatment stratification.

  Study EGAS00001002314

• Cambridge_INTERVAL_SomaLogic_pQTLs

  This dataset contains four data files relating to the Cambridge Interval SomaLogic pQTL study to go with the corresponding genetic data: (1) Genome-wide pQTL summary associations for each analyte. (2) Mapping table for the genetic variants analysed - containing rsID, position and allele information. (3) Normalised quantitative readouts for each analyte, along with covariates used for the pQTL analysis. (4) Table of SOMAmer analytes mapped to their protein targets. Please see the readme file in the dataset for more information.

  Dataset EGAD00001004080

• RNAseq data of brain metastasis samples

  Paired-end RNA sequencing data from 95 brain metastasis samples with different primary origins. Sequencing was performed on the Illumina HiSeq 3000.

  Dataset EGAD50000000799

• Chlamydia trachomatis exploits sphingolipid metabolic pathways during infection of phagocytes

  This study looks at the response of M2 macrophages stimulated with GM-CSF and IL4 for 7 days and 2 days respectively to C. trachomatis infection on an Illumina platform.

  Study EGAS50000000960

• Fibromyalgia versus small fiber neuropathy: Diverse keratinocyte transcriptome signature

  We provide a diverse keratinocyte transcriptome signature between SFN and FMS patients, which may hint towards distinct pathomechanisms of small fiber sensitization and lay the basis for advanced diagnostics in both entities

  Study EGAS00001005004

• Joint-Specific TF Regulation in RA

  The mechanisms responsible for the distribution and severity of joint involvement in rheumatoid arthritis (RA) are not known. To explore whether site-specific fibroblast-like synoviocyte (FLS) biology might be associated with location-specific synovitis and explain the predilection for hand (wrist/metacarpal phalangeal joints) involvement in RA, we generated bulk, whole-genome transcriptomic and chromatin accessibility data from FLS. Samples were matched in age, sex, and were homogeneous in that all had significant joint damage with longstanding disease requiring surgical intervention. Analysis revealed joint-specific patterns of FLS phenotypes, with proliferative, migratory, proinflammatory, and matrix-degrading characteristics observed in resting FLS derived from the hand joints compared with hip or knee. TNF-stimulation amplified these differences, with greater enrichment of proinflammatory and proliferative genes in hand FLS compared with hip and knee FLS. Hand FLS also had the greatest expression of markers associated with an ‘activated' state relative to the ‘resting' state, with the greatest cytokine and MMP expression in TNF-stimulated hand FLS. Predicted differences in proliferation and migration were biologically validated with hand FLS exhibiting greater migration and cell growth than hip or knee FLS. Distinctive joint-specific FLS biology associated with a more aggressive inflammatory response might contribute to the distribution and severity of joint involvement in RA.

  Study phs003633

• Degradation of Janus kinases in CRLF2-rearranged acute lymphoblastic leukemia

  We evaluated the efficacy of proteolysis-targeting chimeras (PROTACs) directed against Janus kinases. Solving the structure of FDA-approved type I JAK inhibitors ruxolitinib and baricitinib bound to the JAK2 JH1 tyrosine kinase domain enabled the rational design and optimization of Cereblon (CRBN)-directed JAK PROTACs utilizing multiple derivatives of JAK inhibitors, linkers and CRBN-specific molecular glues. The resulting JAK PROTACs were evaluated for target degradation by proteomic approaches, and activity tested in CRLF2-rearranged cell line and xenograft models of ALL.

  Study EGAS00001005180