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• We performed whole-exome sequencing of 20 samples (10 actinic keratosis and 10 cutaneous squamous cell carcinoma) to investigate a potential relationship between DNA methylation-based subtypes and genetic mutation patterns (Rodriguez-Paredes et al., Nat Commun 2017)

  Cutaneous squamous cell carcinoma (cSCC) is the second most common skin cancer type and arises from keratinocytes. Most cSCC progress from a UV-induced precancerous lesion termed actinic keratosis (AK). Despite various efforts to characterize these lesions molecularly, the etiology of AK and its progression to cSCC remain only partially understood. Here we have used Infinium MethylationEPIC BeadChips to interrogate the DNA methylation status of about 850.000 CpGs in epidermal preparations from healthy skin, AK and cSCC. Importantly, we found that the premalignant AK samples displayed classical features of cancer methylomes and were highly similar to cSCC methylomes. Further analysis identified typical features of stem cell methylomes, such as a reduced DNA methylation age, non-CpG methylation and stem cell-related keratin and enhancer methylation patterns. Interestingly, this signature was detected only in one half of the AK and cSCC samples, while the other half showed keratin and enhancer methylation patterns that were more closely related to the control epidermis. These findings suggest the existence of two distinct subclasses of AK and cSCC that originate from distinct keratinocyte differentiation stages.

  Study EGAS00001002670

• Healthy control and lung cancer plasma cfDNA samples from various collection tubes

  The dataset contains 6 lung cancer and 60 healthy control plasma cfDNA samples collected in EDTA, PAXGene and Norgen blood collection tubes at various locations. Shallow WGS was performed on an Illumina Novaseq S4 PE150bp. Samples are provided as raw reads without any prior processing.

  Dataset EGAD00001008322

• cfDNA from fractionated and paired unfractionated plasma samples of lung cancer patients

  Plasma from lung cancer patients from EDTA tubes was fractionated using size exclusion chromatography. Fractions 1-5, 7-11, 12-15, 16-20 were pooled, cfDNA was extracted from the fractions and paired unfractionated samples and PE150bp sequencing was performed on an Illumina Novaseq S4 flowcell. Samples are provided as raw reads without any prior processing.

  Dataset EGAD00001009780

• Adenoma development in familial adenomatous polyposis and MUTYH‐associated polyposis: somatic landscape and driver genes

  Familial adenomatous polyposis (FAP) and MUTYH‐associated polyposis (MAP) are inherited disorders associated with multiple colorectal adenomas that lead to a very high risk of colorectal cancer. The somatic mutations that drive adenoma development in these conditions have not been investigated comprehensively. In this study we performed analysis of paired colorectal adenoma and normal tissue DNA from individuals with FAP or MAP, sequencing 14 adenoma whole exomes (eight MAP, six FAP), 55 adenoma targeted exomes (33 MAP, 22 FAP) and germline DNA from each patient.

  Dataset EGAD00001004332

• Lineage Plasticity and Immune Cell Heterogeneity Are Coordinately Dysregulated Through Changes in FOXA1 Expression in Bladder Cancers with Squamous Differentiation

  We performed whole exome sequencing (WES) of paired, macrodissected regions of urothelial carcinoma (UC), not otherwise specified (NOS-UC) and squamous differentiation (SqD) from 21 bladder tumors in which distinct and separable NOS-UC and SqD regions were present (total 42 exomes, in addition to matched normal exomes). Mean tumor mutational burden (TMB) was higher in the SqD versus the NOS-UC regions. Consistent with the higher TMB, the SqD regions also had a higher neoantigen burden than the patient-matched NOS-UC regions. The SqD regions also exhibited higher karyotypic complexity with a higher median ploidy relative to the paired NOS-UC regions. Phylogenetic analysis of the WES data confirmed that the morphologically distinct regions of all 21 tumors arose from a shared precursor with a median of 68 (range 16 – 852) non-synonymous mutations shared between the NOS-UC and SqD regions, and the overall data were indicative of early branched evolution. As whole exome sequencing did not identify a shared mutational alteration or genomic signature unique to the SqD or NOS-UC components, we therefore performed expression profiling of separable SqD and NOS-UC regions of 12 bladder tumors from the WES cohort with RNA quality sufficient for whole transcriptome RNA-sequencing (RNAseq, total of 24 regions). Based on centroid clustering analysis of expression data, all 12 regions of SqD were basal-squamous subtype based on the TCGA molecular classification schema. Notably, 8 of the NOS-UC regions were also basal-squamous subtype, with only four pairs exhibiting discordant transcriptional subtypes (three NOS-UC regions were luminal-infiltrated, one luminal-papillary). To better quantify differences in the transcriptional profiles of the paired NOS-UC and SqD regions, we used single sample gene set enrichment analysis (ssGSEA) to assess for enrichment of luminal or basal-squamous gene expression. ssGSEA analysis revealed that the SqD regions expressed higher levels of basal-squamous genes based on the BASE47 gene set and UPK/KRT gene sets; whereas the matched NOS-UC regions expressed higher levels of luminal genes. These differences in the levels of expression of basal and luminal genes were observed even in cases in which both the NOS-UC and SqD regions were basal-squamous subtype based the TCGA molecular classification schema. Exomes from eight patients in this study have previously been deposited in dbGaP: accession number phs001783 as part of the study "Exome Recapture and Sequencing of Prospectively Characterized Clinical Specimens From Cancer Patients".

  Study phs002357

• Pancreatic Cancer Sequencing Initiative OICR

  Pancreatic Cancer Sequencing Initiative for the International Cancer Genome Consortium at the Ontario Institute for Cancer Research.

  Study EGAS00001000395

• FASTQ files of the RNA-Seq data for the study "Genomic landscape of lung adenocarcinoma in East Asians"

  FASTQ files of the RNA-Seq data for both the normal and tumor samples for the study "Genomic landscape of lung adenocarcinoma in East Asians". For raw read count data as well as other metadata, please download from https://src.gisapps.org/OncoSG_public/study/summary?id=GIS031 by clicking the download icon next to the dataset title.

  Dataset EGAD00001004421

• FASTQ files of the Exome-Seq data for the study "Genomic landscape of lung adenocarcinoma in East Asians"

  FASTQ files of the Exome-Seq data for both the normal and tumor samples for the study "Genomic landscape of lung adenocarcinoma in East Asians". For mutations and copy number variants called by this study, please download from https://src.gisapps.org/OncoSG_public/study/summary?id=GIS031 by clicking the download icon next to the dataset title.

  Dataset EGAD00001004422

• Linking the epigenetic landscape in chronic lymphocytic leukemia to deregulated chromatin networks

  Aberrant chromatin features and epigenetic signaling emerge as an important part of the tumor disease state in chronic lymphocytic leukemia (CLL). However, an integrative analysis of the malignant chromatin landscape is currently missing. Here, we mapped DNA-methylation, nucleosome position, 7 histone modifications, ATAC-seq and the transcriptome in primary CD19+ sorted B-cells from the peripheral blood of CLL patients in comparison to non-malignant lymphocytes of healthy donor reference samples. On the > 50 kb scale we identified global differences with respect to DNA methylation, nucleosome positioning and histone modifications in CLL. Furthermore, a chromatin state annotation was developed to identify deregulated chromatin features of promoters and enhancers in CLL. By integrating these findings with an ATAC-seq based transcription factor binding analysis we identified a set of promoters and enhancers specific to CLL that were enriched in certain transcription factors binding motifs and genes of the BCR signaling pathway. Thus, our study provides an in-depth map of the CLL chromatin landscape and links chromatin state changes at promoters and enhancers to deregulated pathways.

  Study EGAS00001002518

• The impact of BNT162b2 mRNA vaccine against SARS-CoV-2 on adaptive and innate immune responses

  The mRNA-based BNT162b2 protects against severe disease and mortality caused by SARS-CoV-2 through induction of specific antibody and T-cell responses. Much less is known about its broad effects on immune responses against other pathogens. In the present study, we investigated the specific adaptive immune responses induced by BNT162b2 vaccination against various SARS-CoV-2 variants, as well as its effects on the responsiveness of human immune cells upon stimulation with heterologous viral, bacterial, and fungal pathogens. BNT162b2 vaccination induced effective humoral and cellular immunity against SARS-CoV-2 that started to wane after six months. We also observed long-term transcriptional changes in immune cells after vaccination, as assessed by RNA sequencing. Additionally, vaccination with BNT162b2 modulated innate immune responses as measured by the production of inflammatory cytokines when stimulated with various microbial stimuli other than SARS-CoV-2, including higher IL-1/IL-6 release and decreased production of IFN-α. Altogether, these data expand our knowledge regarding the overall immunological effects of this new class of vaccines and underline the need of additional studies to elucidate their effects on both innate and adaptive immune responses.

  Study EGAS00001006818

• Investigation of chromatin accessibility in clear cell renal cell carcinoma using ATAC-seq

  To identify regions of open and accessible chromatin in clear cell renal cell carcinoma (ccRCC), we performed ATAC-seq on the 786-O, A-498, UM-RC-2 ccRCC cell lines, as well as HK-2 normal renal epithelium cell line, cultured under normoxic (20% O2) and hypoxic (0.05% O2) conditions. Data are provided in raw fastq and processed narrowPeak fomats. Data were processed using the nf-core atacseq pipeline.

  Dataset EGAD50000001885

• Vitamin-D-Kids Asthma

  The Vitamin D Kids Asthma Study (VDKA) was a 48-week multicenter randomized, double-blinded, placebo-controlled trial of vitamin D3 for severe asthma exacerbations in children 6-16 years old, recruited from February 28, 2016 to September 20, 2019. An ancillary study for nasal sampling was conducted at the Pittsburgh site. Prior to randomization, participants completed questionnaires and underwent collection of nasal samples for gene expression studies. VDKA was approved by the IRBs of all participating institutions, and the ancillary study was approved by the IRB of the University of Pittsburgh. Written parental consent was obtained for participating children, from whom written assent was also obtained.

  Study phs004051

• RNA-sequencing data from 195 B-cell precursor acute lymphoblastic leukemias and mate pair whole genome sequencing data from 15 B-cell precursor acute lymphoblastic leukemias

  Fusion genes are potent driver mutations in cancer. In this study, we delineate the fusion gene landscape in a consecutive series of 195 pediatric B-cell precursor acute lymphoblastic leukemia (BCP ALL). Using RNA-sequencing, we find in-frame fusion genes in 127 (65%) cases, including 27 novel fusions. We describe a new subtype characterized by recurrent IGH-DUX4 or ERG-DUX4 fusions, representing 4% of cases, leading to overexpression of DUX4 and frequently co-occurring with intragenic ERG deletions. Furthermore, we identify a subtype characterized by an ETV6-RUNX1-like gene expression profile and coexisting ETV6 and IKZF1 alterations. Taken together, this study provides a detailed overview of fusion genes in pediatric BCP ALL and adds new pathogenetic insights, which may improve risk stratification and provide novel therapeutic options in this disease.

  Study EGAS00001001795

• Single-cell analysis reveals fibroblast clusters linked to immunotherapy resistance in cancer

  A subset of Cancer-Associated Fibroblasts (CAF-S1) mediates immunosuppression in breast cancers (BC), but its heterogeneity and its impact on immunotherapy response remain unknown. Here, we identify 8 CAF-S1 clusters by analyzing more than 18000 single CAF-S1 fibroblasts from BC. We validate the 5 most abundant clusters by flow cytometry and in silico analyses in other cancer types, highlighting their relevance. Myofibroblasts from clusters 0 and 3, characterized by extra-cellular matrix proteins and TGF signaling respectively, are indicative of primary resistance to immunotherapies. Cluster 0 up-regulates PD-1 and CTLA-4 protein levels in regulatory T lymphocytes (Tregs), which in turn increases CAF-S1 cluster 3 cellular content. Thus, our study highlights a positive feedback loop between specific CAF-S1 clusters and Tregs and uncovers their role in immunotherapy resistance.

  Study EGAS00001004030

• Diagnostic Genomic Analysis is Prognostic in AYA ALL Patients Treated on a MRD-Stratified Paediatric Protocol

  Background: Over the last decade, next generation sequencing has enabled classification of multiple new recurrent genomic drivers of acute lymphoblastic leukemia (ALL). We provide a comprehensive genomic survey of adolescent and young adult (AYA) patients treated on the Australasian Leukaemia and Lymphoma Group (ALLG) ALL06 study. ALL06 clinical trial described the efficacy and tolerability of AYA ALL patients aged 15-39 years treated on a single minimal residual disease (MRD)-stratified platform. In this study we have taken the ALL06 cohort and retrospectively performed comprehensive genomic analyses assessing response of AYA patients with various genomic subtypes treated with a paediatric approach. Methods: Genomic risk classification of B- and T-ALL patients (n=57) enrolled to the study was based on mRNA-Sequencing, MLPA, immunophenotyping and cytogenetics. Results: Using this approach, 36/40 (90%) B- and 13/17 (76.5%) T-ALL patients were classified according to genomic risk. We have linked outcome data with each patient’s genomic risk and found a strong correlation between adverse genomic risk and MRD at the end of consolidation, translating to inferior overall and relapse free survival. Patients with adverse risk genomics who achieved negative MRD status had improved responses compared to those with persistent MRD. Patients with standard risk genomics had excellent responses regardless of their MRD status. Conclusion: Our data argue strongly for incorporation of a genomic risk classification into future ALL treatment paradigms at the time of diagnosis.

  Study EGAS50000000752

• Proteogenomic analysis reveals RNA as a source for tumor-agnostic neoantigen identification (H021)

  Systemic pan-tumor analyses may reveal the significance of common features implicated in cancer immunogenicity and patient survival. Here, we provide a comprehensive multi-omics data set for 32 patients across 25 tumor types for proteogenomic-based discovery of neoantigens. By using an optimized computational approach, we discover a large number of tumor-specific and tumor-associated antigens. To create a pipeline for the identification of neoantigens in our cohort, we combine DNA and RNA sequencing with MS-based immunopeptidomics of tumor specimens, followed by the assessment of their immunogenicity and an in-depth validation process. We detect a broad variety of non-canonical HLA-binding peptides in the majority of patients demonstrating partially immunogenicity. Our validation process allows for the selection of 32 potential neoantigen candidates. The majority of neoantigen candidates originates from variants identified in the RNA data set, illustrating the relevance of RNA as a still understudied source of cancer antigens. This study underlines the importance of RNA-centered variant detection for the identification of shared biomarkers and potentially relevant neoantigen candidates.

  Study EGAS00001006706

• Tumor Profiler Project - AML scDNA data

  The dataset contains single-cell DNA seq data from 21 patients with Acute Myeloid Leukemia (AML). Samples were collected from bone marrow or blood. Sequencing was performed in paired-end mode and sequencing data is provided in fastq format.

  Dataset EGAD50000000824

• Tumor Profiler Project - AML scRNA data

  The dataset contains single-cell RNA seq data from 23 patients with Acute Myeloid Leukemia (AML). Samples were collected from bone marrow or blood. Sequencing was performed in paired-end mode and sequencing data is provided in fastq format.

  Dataset EGAD50000000823

• Tumor Profiler Project - AML bulk transcriptomics data

  The dataset contains bulk transcriptomics data from 23 patients with Acute Myeloid Leukemia (AML). Samples were collected from bone marrow or blood. Sequencing was performed in paired-end mode and sequencing data is provided in fastq format.

  Dataset EGAD50000000822

• Genomic analysis of pancreatic neuroendocrine tumour with MEN1, ATRX, or DAXX mutations

  This dataset includes 52 samples from 19 individuals with pancreatic neuroendocrine tumours. These samples were analyzed using RNA-sequencing, whole-exome sequencing, shallow (~0.3x) whole-genome sequencing, and a 21-gene panel targeted capture sequencing. Everything was sequenced using the Illumina HiSeq and is provided in BAM or FASTQ format.

  Dataset EGAD00001006001

• sWGS data from 362 tumor with non muscle invasive bladder cancer and 30 blood samples (15 males and 15 females)

  A better understanding of the molecular landscape of non-muscle-invasive bladder cancer (NMIBC) is essential to improve risk assessment and identify potential therapeutic targets. Here, we perform a comprehensive genomic analysis of patients diagnosed with NMIBC based on whole-exome- (n=438), shallow whole-genome- (n=362), and total RNA-sequencing (n=414). This dataset contains 876 BAM files corresponding to the full WES dataset. This dataset contains 392 BAM files corresponding to the full sWGS dataset. Tumor samples were sequenced to median coverage of 2.14x (1.24-9.01).

  Dataset EGAD50000000732

• Genomic signatures define three subtypes of EGFR-mutant stage II-III non-small-cell lung cancer with distinct adjuvant therapy outcomes

  This dataset contains targeted sequencing data of 204 surgical samples from resected NSCLC. Genomic profiling identifies five predictive biomarkers, which is then integrated into the Multiple-gene INdex to Evaluate the Relative benefit of Various Adjuvant therapies (MINERVA) score. The MINERVA score categorizes patients into three subgroups with relative disease-free survival and overall survival benefits from either adjuvant gefitinib or chemotherapy. This study demonstrates that predictive genomic signatures could potentially stratify resected EGFR-mutant NSCLC patients and provide precise guidance towards future personalized adjuvant therapy.

  Dataset EGAD00001008157

• RNASeq of bone marrow endothelial cells upon regeneration, (fetal) niche formation, and steady-state.

  Comprehensive transcriptional characterization of bone marrow endothelial cells by RNA sequencing was performed to determine the molecular properties/signatures of endothelium during bone marrow recovery and niche formation. Regenerative bone marrow endothelium was FACS-isolated from bone marrow aspirates of Acute Myeloid Leukemia patients 17 days after receiving chemotherapy (n=3). Niche-forming endothelial cells were FACS-isolated from fetal bones (gestational age 15-20 weeks) (n=3). Healthy adult bone marrow endothelial cells (n=7) were used as steady-state controls. cDNA was prepared using the SMARTer procedure (SMARTer Ultra Low RNA Kit, Clonetech). The provided file type is FASTQ.

  Dataset EGAD00001003904

• RNA-Seq data of hepatoma (Huh7 derived) and Ph5CH cells and primary hepatocytes

  The innate immune response of cells of hepatic origin (Huh7, Huh7.5, PH5CH and primary human hepatocytes (PHH), 66 samples) was analyzed by transcriptome analysis (RNAseq) upon supernatant delivery or transfection of synthetic dsRNA (poly(I:C)). Expression of TLR3 and RIG-I was reconstituted by lentiviral transduction in Huh7 and Huh7.5 cells. The sequencing is single RNA-Seq on an Illumina HiSeq 4000 with the Illumina TruSeq stranded mRNA kit.

  Dataset EGAD00001007083

• Sequencing of liver cancer cell lines

  Liver cancer is a dreadful disease with limited therapeutic options. How to translate genomic findings into biomarkers and precision treatment is challenging. A large cell line-based platform was established, termed as Liver Cancer Model Repository. Heterogeneities in patients were faithfully recapitulated by 81 liver cancer cell lines at genomic and transcriptomic levels. This platform provides a rich resource and models to study cancer drivers and drug responses in liver cancer.

  Study EGAS00001002237

• Long Read sequencing data from 4 tumor/germline samples with non muscle invasive bladder cancer

  A better understanding of the molecular landscape of non-muscle-invasive bladder cancer (NMIBC) is essential to improve risk assessment and identify potential therapeutic targets. Here, we perform a comprehensive genomic analysis of patients diagnosed with NMIBC based on whole-exome- (n=438), shallow whole-genome- (n=362), and total RNA-sequencing (n=414). Additionally, tumor/germline samples from 4 patients were sequenced using Oxford Nanopore technology. This dataset contains 8 BAM files corresponding to the Long read sequencing data.

  Dataset EGAD50000000731

• WES data from 438 tumor/germline samples with non muscle invasive bladder cancer

  A better understanding of the molecular landscape of non-muscle-invasive bladder cancer (NMIBC) is essential to improve risk assessment and identify potential therapeutic targets. Here, we perform a comprehensive genomic analysis of patients diagnosed with NMIBC based on whole-exome- (n=438), shallow whole-genome- (n=362), and total RNA-sequencing (n=414). This dataset contains 876 BAM files corresponding to the full WES dataset. Tumor and matched germline DNA were sequenced to a mean coverage of 132x (35x-338x) and 128x (31x-302x), respectively.

  Dataset EGAD50000000730

• RNA-Seq data from study: Molecular underpinnings of dedifferentiation and aggressiveness in chromophobe renal cell carcinoma

  The ChRCC study RNA-Seq dataset contains raw whole transcriptome sequencing data of 16 tumor and 6 adjacent normal samples from 7 UTSW patients, who have consented to depositing their genomic data to public repository. RNA-Seq was performed using 50bp single-end on a HiSeq2500 platform (Illumina, San Diego, CA, USA). 50M reads per sample on average. The raw data is in fastq format.

  Dataset EGAD50000000416

• Genomic Landscape of Malignant Peripheral Nerve Sheath Tumor-like Melanoma

  Malignant peripheral nerve sheath tumor (MPNST)-like melanoma is a rare malignancy with overlapping characteristics of both neural sarcoma and melanoma. The genomics of MPNST-like melanoma have not been previously described. In this study, we performed whole exome sequencing analysis in 8 samples from 6 patients diagnosed with MPNST-like melanoma. Our results demonstrate that, although MPNST-like melanoma shares oncogenic alterations common to both cutaneous melanoma and MPNST, it also presents unique genomic alterations not previously described in neither of the malignancies.

  Dataset EGAD00001006999

• Long-read sequencing of diagnosis and post-therapy medulloblastoma reveals complex rearrangement patterns and epigenetic signatures

  Cancer genomes harbor a broad spectrum of structural variants (SV) driving tumorigenesis, a relevant subset of which are likely to escape discovery in short reads. We employed Oxford Nanopore Technologies (ONT) sequencing in a paired diagnostic and post-therapy medulloblastoma to unravel the haplotype-resolved somatic genetic and epigenetic landscape. We assemble complex rearrangements and such associated with telomeric sequences, including a 1.55 Megabasepair chromothripsis event. We uncover a complex SV pattern termed "templated insertion thread", characterized by short (mostly less than 1kb) insertions showing prevalent self-concatenation into highly amplified structures of up to 50kbp in size. Templated insertion threads occur in 3% of cancers, with a prevalence ranging to 74% in liposarcoma, and frequent colocalization with chromothripsis. We also perform long-read based methylome profiling and discover allele-specific methylation (ASM) effects, complex rearrangements exhibiting differential methylation, and differential promoter methylation in seven cancer-driver genes. Our study shows the potential of long-read sequencing in cancer.

  Study EGAS00001006576

• Kidney_tumour_DNA

  This is a bulk DNA and RNA sequencing study of human renal tumours

  Study EGAS00001002486

• Compound heterozygous variants in LAMC3 in association with posterior periventricular nodular heterotopia

  Periventricular nodular heterotopia is a malformation of cortical development characterized by nodules of abnormally migrated neurons.

  Study EGAS00001004793

• Bulk and single-cell RNA-sequencing data from five lines of human iPSC-derived (hiPSC-derived) astrocytes (3 in-house and 2 commercial lines), both alone and in co-culture with neurons, to define the molecular response of astrocytes to misfolded alpha-synuclein

  RNA editing is a post transcriptional mechanism that targets changes in RNA transcripts to modulate innate immune responses. We report the role of astrocyte specific, ADAR1 mediated RNA editing in neuroinflammation in Parkinson’s disease. We generated hiPSC-derived astrocytes, neurons and co-cultures and exposed them to small soluble alpha-synuclein aggregates. Oligomeric alpha-synuclein triggered an inflammatory glial state associated with TLR activation, viral responses, and cytokine secretion. This reactive state resulted in loss of neurosupportive functions, and the induction of neuronal toxicity. Notably, interferon response pathways were activated leading to upregulation, and isoform switching of the RNA deaminase enzyme, ADAR1. ADAR1 mediates A-to-I RNA editing, and increases in RNA editing were observed in inflammatory pathways in cells, as well as in post-mortem human PD brain. Aberrant, or dysregulated, ADAR1 responses and RNA editing may lead to sustained inflammatory reactive states in astrocytes triggered by alpha-synuclein aggregation, and this may drive the neuroinflammatory cascade in Parkinson’s.

  Study EGAS50000000751

• Human CD4+ T cells regulate peripheral immune responses in rheumatoid arthritis via IGFL2

  To elucidate the role of the immunoregulatory mechanisms of human CD4+ T cells, we analyzed CD4+ T cells in PBMC, synovium and synovial fluid using single-cell RNA sequencing (scRNA-seq). We identified insulin-like growth factor (IGF) like family member 2 (IGFL2), an evolutionary novel paralogous inflammatory factor found exclusively in primates. ScRNA-seq of RA synovium showed that IGFL2 is specifically expressed by CD4+ T cells, predominantly within peripheral helper T (Tph) cells, with upregulation correlating to disease severity. IGFL2 promotes TGF-��-induced CXCL13 production in CD4+ T cells. In addition, IGFL2 activates NF-��B signaling and induces monocyte gene signatures associated with pathogenic macrophages from RA synovial tissue, including CXCL10 and CXCL9. Notably, blood IGFL2 protein levels significantly correlate with RA disease severity and effectively discriminate RA patients. These findings highlight the substantial involvement of IGFL2 in RA pathogenesis, emphasizing how human CD4+ T cells exert pleiotropic regulation of local immune responses via this novel primate-specific soluble factor.

  Study JGAS000727

• A novel subset of human CD33+ haematopoietic stem cells characterized at single-cell resolution

  Elucidation of the identity and diversity of mechanisms that sustain long-term human blood cell production remains an important challenge. Previous studies indicate that, in adult mice, this property is ultimately vested in cells uniquely identified by their ability to clonally regenerate detectable levels of mature blood cells in serially transplanted recipients. We now present a combined multi-parameter analysis of the molecular features of very primitive human cord blood cells that display different cell output activities in vitro and in vivo. These analyses identified a new, prospectively separable, but still functionally heterogeneous, subset of long-term human blood-forming cells. Single-cell measurements of their transcriptional, DNA methylation and 40-protein content and of closely related phenotypes revealed numerous subtle, but consistent differences both within and between each subset analyzed. These results suggest that multiple regulatory mechanisms underlie the functional heterogeneity exhibited by clonally tracked human blood cell precursors with long-term output abilities.

  Study EGAS00001002826

• Integrated genetic and epigenetic analysis defines novel molecular clusters in rhabdomyosarcoma

  Rhabdomyosarcoma (RMS) is the most common soft tissue sarcoma in childhood. To unravel the genetic/epigenetic basis of RMS, we studied 60 RMS cases using whole exome/transcriptome sequencing, copy number (CN) profiling, and DNA methylome analysis. Based on DNA methylation patterns, RMS was clustered into 4 distinct subtypes, which exhibited remarkable correlation with mutation/CN profiles, histological phenotypes, and clinical behaviors. A1 and A2 subtypes, especially A1, largely corresponded to alveolar histology with frequent PAX3/7 fusions and alterations in cell cycle regulators. In contrast, mostly showing embryonal histology, both E1 and E2 subtypes were characterized by high frequency of CN alterations and/or allelic imbalances, FGFR4/RAS/AKT pathway mutations and PTEN mutations/methylation and in E2, also by p53 inactivation. Despite generally poor prognosis in RMS, patients in E1 cluster exceptionally showed excellent prognosis. Our results highlight the close relationship between DNA methylation status and gene mutations and biological behavior in RMS.

  Study EGAS00001000884

• Leukemia Data Access committee for the deposited data. The committee consists of the principal investigators for the data set.

  Dac EGAC00001003565

• Origination of Ovarian Cancer is Dependent on Specific Aneuploidy Landscape

  Ovarian high-grade serous carcinoma (HGSC), a highly chromosomally instable malignancy, develops through sequential stages of precursors in fallopian tubes including histologically unremarkable but TP53 mutated clones (p53 signature) and serous tubal intraepithelial carcinoma (STIC). Here, we applied RealSeqS to assess aneuploidy in 127 microdissected tubal regions. We found nearly all p53 signatures lost the entire Chr17 chromosome, offering a “two-hit” mechanism of both TP53 and BRCA1 in BRCA1 germline mutation carriers. Proliferatively active STICs harbor gains of 19q12 (CCNE1), 19q13.2, 8q24 (MYCyc), or 8q arm, while proliferatively dormant STICs show 22q loss. Based on aneuploidy patterns in a training set (n= 67), we developed an algorithm, REAL-FAST, to classify NFTE and STICs into 5 clusters. In an independent validation set (n= 72), REAL-FAST was able to detect STIC/HGSC with high sensitivity and specificity. Taken together, REAL-FAST promises a molecular test for diagnosing HGSC precursor lesions based on specific aneuploidy patterns.

  Study EGAS00001007220

• Transcriptional Response to Hypoxia in iPSC-Derived Endothelial Cells from a High Altitude Adapted Population

  We established lymphoblastoid cell lines from 10 adult individuals of Tibetan ancestry living in the Chicago area. These lines were reprogrammed to induced pluripotent stem cells (iPSC). We validated genetic ancestry by genome-wide SNP array genotyping and population genetic analyses. After being subjected to standard quality control testing iPSCs were differentiated into endothelial cells. Following differentiation, endothelial cells were isolated via a pull down protocol using beads coated with an antibody for a canonical surface cell marker of the vascular endothelium (CD144). Purified vascular endothelial cells were cultured in parallel in normoxia (20% O2) and hypoxia (1% O2) for 48 hours prior to harvesting and processing for bulk RNA-sequencing. We provide imputed genotype data and bulk RNA-sequencing data in normoxia and in hypoxia for each of the 10 individuals. We also provide multiplexed scRNA-sequencing data for the 10 Tibetan individuals pooled with 10 CHB individuals from the 1000 Genome Project. Additionally, we provide scRNAseq data for the cardiomyocytes derived from the same iPSC lines from the Tibetan individuals pooled together with cardiomyocytes derived from iPSC lines of 10 CHB individuals from the 1000 Genome Project. Lymphoblastoid cell lines from the CHB were reprogrammed to iPSCs and differentiated to cardiomyocytes using the same protocols as used for the Tibetans. The batches of 4 lines were balanced by sex and population. These iPSC-derived cardiomyocytes were cultured in hypoxia (1% O2) for 48 hours and subjected to scRNAseq in pooled batches of 3 or 4 lines. The CHB individuals included in this analysis were: NA18528, NA18531, NA18557, NA18596, NA18606, NA18608, NA18614, NA18619, NA18633, and NA18748.

  Study phs003758

• Exploring germline and somatic mutagenesis in the extended family with germline pathogenic variant in POLD1

  This study aimed to estimate the influence of POLD1 L474P on somatic and germline mutagenesis. We studied the mutation rate and spectra in germline and soma in an extended family harboring the POLD1 c.1421T>C p.(Leu474Pro) pathogenic variant. The study includes WGS data for DNA extracted from blood, fibroblasts or buccal swabs from the 16 family members, from DNA obtained single-cell derived colonies obtained from immortalized fibroblasts for 8 of 16 family members and from the same single-cell derived immortalized fibroblasts after approximately 40 passages for 6 out of 8 family members. Additionaly, study includes WXS sequencing for 1 tumor FFPE sample and adjacent normal tissue from the individual from one family member.

  Study EGAS00001006434

• Validation of AML Mutational Screening

  We recently worked-up a pulldown protocol for studying 21 genes recurrently mutated in AML (Study1770). Our manuscript is currently under revision and to address the reviewers' comments we need to validate some mutations by re-sequencing. In this add-on study we will be using PCR followed by MiSeq for this purpose.

  Dataset EGAD00001000445

• Targeting AXL Kinase Uniquely Sensitizes Therapy-Insensitive Leukemic Stem and Progenitor Cells to Venetoclax Treatment in Acute Myeloid Leukemia

  The abundance of genetic abnormalities and phenotypic heterogeneities in AML pose significant challenges to developing improved treatments. Here we demonstrated that a key GAS6/AXL axis is highly activated in AML patient cells, particularly in leukemic stem cells. We developed a potent, selective AXL inhibitor that has excellent pharmaceutical properties and efficacy against preclinical patient-derived xenotransplantation models of AML. Importantly, inhibition of AXL sensitized AML stem/progenitor cells to venetoclax treatment, with strong synergistic effects in vitro and in vivo. Mechanistically, single-cell RNA-sequencing and functional validation studies uncovered that AXL inhibition or in combination with venetoclax potentially targets intrinsic metabolic vulnerabilities of AML stem/progenitor cells, which shows a distinct transcriptomic profile and inhibits mitochondrial oxidative phosphorylation. These findings have direct translational impact on the treatment of AML and other cancers with high AXL activity.

  Study EGAS00001004663

• Multi-omics integration reveals only minor long-term molecular and functional sequelae in immune cells of individuals recovered from COVID-19

  The majority of COVID-19 patients experience mild to moderate disease course and recover within a few weeks. An increasing number of studies characterized the long-term changes in the specific anti-SARS-CoV-2 immune responses, but how COVID-19 shapes the innate and heterologous adaptive immune system after recovery is less well known. To comprehensively investigate the post-SARS-CoV-2 infection sequelae on the immune system, we performed a multi-omics study by integrating single-cell RNA-sequencing, single-cell ATAC-sequencing, genome-wide DNA methylation profiling, and functional validation experiments in convalescent COVID-19 and healthy individuals. We showed that immune responses generally recover without major sequelae after COVID-19. However, subtle differences persist at the transcriptomic level in monocytes, with downregulation of the interferon pathway, while DNA methylation also displays moderate changes in convalescent COVID-19 individuals. However, these differences did not affect the cytokine production capacity of PBMCs upon different bacterial, viral, and fungal stimuli, although baseline release of IL-1RA and IFN?? was higher in convalescent individuals. In conclusion, despite minor differences in epigenetic and transcriptional programs, the immune system of convalescent COVID-19 patients largely recovers to the homeostatic level of healthy individuals.

  Study EGAS00001005529

• Multi-omic dataset of neuroendocrine neoplasm organoids

  This dataset corresponds to one of the first biobanks for the understudied neuroendocrine neoplasms from multiple grades and body sites (lung, pancreas, small intestine). It contains whole-genome sequencing data for original tumors, patient-derived tumor organoids at multiple passages, and matched normal tissue, and RNA-seq data for the original tumor and patient-derived tumor organoids.

  Study EGAS00001005752

• The dataset for "Validation of cfDNA fragmentome analyses for early detection of liver cancer"

  The dataset for “Validation of cfDNA fragmentome analyses for early detection of liver cancer” includes 380 cram files from whole genome next-generation sequencing on the Illumina NovaSeq 6000 with 10x coverage. The samples analyzed include plasma samples from patients with cancer and liver disease.

  Dataset EGAD00001015538

• ATAC-Seq on OCIAML-22 Fractions

  The donor AML patient (unsorted) that was used to generate OCI-AML22 was expanded for 3-4 months, then sorted for the indicated fraction (CD34p: CD34+; CD34m: CD34-)

  Study EGAS00001006511

• Integrative and comparative genomic analyses identify clinically relevant groups of pulmonary carcinoids and unveil the supra-carcinoids

  Multi-omic data for lung neuroendocrine neoplasms, including the first multi-omic sequencing data for the understudied lung atypical carcinoids. The data includes Whole-exomes, whole-genomes, RNA-seq, and EPIC 850K methylation array data.

  Study EGAS00001003699

• PREGO reference panel - 3234 individuals from Western France. Individuals' birthplaces are available in epsg.io/2154 (RGF93 v1 / Lambert-93 -- France) coordinates.

  Study EGAS00001007764

• whole genome sequence of liver cancer

  There are six samples with three blood samples and three organids

  Dataset EGAD00001009841

• Whole blood RNAseq from a large ALS case-control study at Univ of Michigan

  This dataset consists of 388 bulk RNA-seq data (sorted aligned BAM files) from whole blood of ALS participants meeting the Gold Coast definition of ALS during their clinical visit (n=204) and healthy controls (n=184) at the University of Michigan (UM). Samples were collected as part of the UM Pranger ALS Clinic between 2011-2021, and prepared either using poly-A selection of rRNA depletion (see Experiments). RNAseq was performed on the NovSeq 6000 S4 at the UM Advanced Genomics Core, resulting in 150bp paired-end reads. Raw reads were trimmed using Cutadapt (v2.3) and aligned to hg38 using STAR (v2.5.3a). Age provided is the age at blood sample collection date. The related paper Zhao, Y., et al. 2025 included 694 samples/participants, and 388 out of the 694 participants consented to share their individual-level data.

  Dataset EGAD50000001488