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• The transcriptomic response of skeletal muscle in life-long high-level trained and untrained men and women after acute exercise

  To investigate the influence of lifelong exercise training on the response of skeletal muscle to a bout of acute exercise we generated global transcriptomic data from long-term endurance (8 men, 8 women) and strength (8 men, 8 women) trained individuals and healthy age-matched untrained controls (8 men, 8 women). Skeletal muscle biopsies were taken from M. vastus lateralis before, directly after, and after 1h and 3hrs following acute exercise. All subjects completed one bout of acute endurance exercise and one bout of acute resistance exercise, separated by 4-8 weeks. All 384 samples were multiplexed in 4 lanes and sequenced (2x250bp paired end) on the Illumina NovaSeq 6000.

  Dataset EGAD00001008663

• Genomic and immune signatures predict clinical outcome in newly diagnosed multiple myeloma treated with immunotherapy regimens

  In this study we performed whole genome sequencing on matched tumor-normal CD138+ bone marrow mononuclear cells from 60 patients with newly diagnosed multiple myeloma treated with daratumumab, carfilzomib, lenalidomide, and dexamethasone (NCT03290950-MANHATTAN trial). In addition, we performed 5’-single-cell RNA-sequencing (10X Genomics) coupled with V(D)J sequencing and capture of the surface protein markers (TotalSeq-C, Biolegend) of the CD138- bone marrow mononuclear cells to interrogate the composition of the immune microenvironment at baseline and after eight cycles of induction therapy in 22 patients with newly diagnosed multiple myeloma. Samples were multiplexed using hashtag oligo.

  Dataset EGAD00001011132

• Broad utility of ultrasensitive analysis of ctDNA dynamics across solid tumors treated with immunotherapy

  Prior studies have suggested the biomarker potential of plasma circulating tumor DNA (ctDNA) in cancer patients treated with immune checkpoint inhibitors (ICIs). In order to characterize the potential role of ultrasensitive ctDNA detection in the management of these patients we have performed tumor whole-genome-informed, ultrasensitive ctDNA analysis—tracking approximately 1,800 tumor-specific mutations per patient—in a retrospective cohort (n=136) and a prospective validation cohort (n=66) across 24 cancer types treated with ICIs alone or in combination with bispecific antibodies or immune cell engagers. Analyzing 1,455 longitudinal samples, we found that ctDNA molecular response measured as early as 3 weeks after treatment initiation correlated with improved progression-free and overall survival, while ctDNA clearance at any time strongly correlated with radiological response and prolonged survival. Additionally, ctDNA dynamics distinguished true progression from pseudoprogression and predicted outcomes in patients receiving continued immunotherapy beyond initial progression. This study highlights the broader applicability of ultrasensitive ctDNA as a biomarker across cancer types and immunotherapy modalities.

  Study EGAS50000001333

• CNA differences between RNA-based subtypes of PDAC

  Pancreatic ductal adenocarcinomas (PDAC) have a dismal prognosis with a 5-year survival of <5%. Chemoresistance and recurrences, seen in approximately 70% of PDAC patients, may partly be explained by intratumor heterogeneity (ITH) through which tumors may develop ‘escape routes’. In the Pancreas Multibiopsy (PM)-project we have obtained multiple fragments from pancreatic and other peri-ampullary carcinomas in order to reveal potential ITH and identify genetic aberrations that predict outcome after surgery and response to chemotherapy. CNA-profiles were used to complement the characterization of liabilities in PDAC that we identified previously using RNAseq in the form of epithelial, secretory, compound pancreatic, and mesenchymal subgroups that showed survival outcomes. Comparison of CNA-profiles between these transcriptomics-based subgroups (with 8, 3, 6, and 6 tumors respectively per group) showed differences, ranging from ‘quiet’(i.e. hardly any CNA) to ‘wild’(i.e. lots of CNA), but these were not statistically significant (Chi2 0.09). When differentiating between the classical and basal-like molecular subtypes of PDAC differences in CNA (high or low) were even less statistically significant (Chi2 0.292).

  Study EGAS50000001218

• Circulating Tumor DNA Analysis Detects Minimal Residual Disease and Predicts Recurrence in Patients with Stage II Colon Cancer

  Detection of circulating tumor DNA (ctDNA) after resection of stage II colon cancer may identify those at the highest risk of recurrence and help inform adjuvant treatment decisions. We used massively-parallel-sequencing–based assays to evaluate the ability of ctDNA to detect minimal residual disease in 1046 plasma samples from a prospective cohort of 230 patients with resected stage II colon cancer. In patients not treated with adjuvant chemotherapy, ctDNA was detected post-operatively in 14 of 178 (7.9%) patients, 11 (79%) of whom had recurred at a median follow-up of 27 months; recurrence occurred in only 16 (9.8 %) of the 164 patients with negative ctDNA (HR, 18; 95% confidence interval [CI], 7.9 to 36; P&lt;0.001). In patients treated with chemotherapy, the presence of ctDNA following completion of chemotherapy was also associated with an inferior recurrence-free survival (HR, 11; 95% CI, 1.8 to 68; P=0.001). ctDNA detection after stage II colon cancer resection provides direct evidence of residual disease and identifies patients at very high risk of recurrence.

  Study EGAS00001001839

• Single-cell analysis of airway samples identifies immune cell activation correlating with COVID-19 disease severity

  To investigate the immune response and mechanisms associated with severe COVID-19, we performed single-cell RNA-seq on nasopharyngeal and bronchial samples from 19 clinically well-characterized patients with moderate or critical disease and from 5 healthy controls. We identified airway epithelial cell types and states vulnerable to SARS-CoV-2 infection. In COVID-19 patients, epithelial cells showed an average threefold increase in expression of the SARS-CoV-2 entry receptor ACE2, which correlated with interferon signals by immune cells. Compared with moderate cases, critical cases exhibited stronger interactions between epithelial and immune cells, as indicated by ligand–receptor expression profiles, and activated immune cells , including inflammatory macrophages expressing CCL2, CCL3, CCL20, CXCL1, CXCL3, CXCL10, IL8, IL1B and TNF . The transcriptional differences in critical cases compared with moderate cases likely contribute to clinical observations of heightened inflammatory tissue damage, lung injury and respiratory failure. Our data suggest that pharmacologic inhibition of the CCR1 and/or CCR5 pathways may suppress immune hyperactivation in critical COVID-19.

  Study EGAS00001004481

• Single Cell, Whole Genome Analysis of the Aging Human Cardiomyocytes

  In this study we have sequenced single cardiomyocytes from 12 individuals (ages from 0.4 to 82 yrs.). We have identified and characterized the somatic single-nucleotide variants (sSNVs). Our study indicates that cardiomyocyte sSNVs increased with age with distinctive mutational signatures.

  Study phs002284

• RNA sequencing of untreated and treated KRAS-mutated metastatic colorectal cancer PDX-derived organoids.

  RNA sequencing was performed on patient-derived xenograft (PDX)-derived organoid models of metastatic colorectal cancer (mCRC). The aim of this study was to characterize the transcriptional landscape of KRAS-mutant mCRC cells in response to therapeutic strategies targeting the EGFR and KRAS signaling pathways. Transcriptomic profiling was conducted following drug treatments to investigate molecular changes associated with single and combination therapies. A total of 24 samples were analyzed.

  Dataset EGAD50000002443

• scRNAseq of fresh CRC punch biopsies

  The dataset includes single-cell RNAseq data generated by Plate-Seq technology from scDiscoveries. The dataset contains samples from a total of 5 different early CRC biobank patients (pt5, pt11, pt13, pt14, pt16) from 4 different sequencing runs. Punch biopsies of different regions of the tumor (Core, Invasive front and, if available, Adenoma) were FACS sorted onto plates prior to sequencing.

  Dataset EGAD50000002203

• Genomic and Transcriptomic sequencing of neuroblastoma patient

  Genomic and Transcriptomic single-cell sequencing of neuroblastoma patient. Data represents one 96-well plate that was processed with G&T sequencing, resulting in genomic and transcriptomic data from the same single cells. Dataset contains 95 bam files containing the DNA sequencing data and 95 bam files containing the RNA sequencing data.

  Dataset EGAD50000000728

• GCAT| WGS Imputation Panel V1

  This dataset includes the .hap, .legend and .sample files from the GCAT|Panel (Iberian reference panel), built from 785 samples, after QC, from the 808 WGS GCAT cohort, including 30.3M SNVs, 5M Indels and 89K SVs. This resource has been generated using Shapeit4 and WhatsHap software. Technology used HiSeq 4000, read length 150 bp, inner mate disatance 300 bp.

  Dataset EGAD00010002153

• Molecular portraits of breast cancer diagnosed during pregnancy

  The aim of this study was to compare the mutational landscape of breast cancer diagnosed during pregnancy (BCP) and breast cancer from age/stage non-pregnant patients (controls). We present whole genome sequencing data (Illumina HiSeq X ten platform) of tumor and matched normal tissues from 35 BCP patients and 20 controls. This work provides important novel biological insights and a unique resource to study the biology of breast cancer in young women and how pregnancy could modulate tumor biology.

  Dataset EGAD00001004353

• DNA-seq FASTQ files from 16 carriers of the BMPR2 p.Arg491Gln mutation in a family affected by HPAH

  Paired-end DNA-seq FASTQ files from 16 carriers of the BMPR2 p.Arg491Gln mutation in a family affected by hereditary pulmonary arterial hypertension (HPAH). Whole genome sequencing of these samples was performed in an Illumina HiSeq 4000 instrument. Libraries were prepared using the Fisher PE Kit (Kapa Biosystems). Each sample was multiplexed across flowcells and lanes, leading to a total number of 86 FASTQ files.

  Dataset EGAD00001005756

• Next-generation sequencing data derived from patient single cells or clonal colonies

  The following samples were generated from the patient samples used in the study: - Bulk DNA sequencing specifically targeting mutated sites of interest derived from clonal cell populations (288 monoclonal colonies - 2 replicates). - Targeted Muta-seq method (Patient P342: 2208 cells, Patient HRK: 1066 cells, Patient LAK: 618 cells, Patient P101: 1080 cells) - Smart-seq2 method (Patient P342 - 768 individual cells).

  Dataset EGAD00001006228

• RNA-seq of endometrial organoids from MRKH patients and controls grown under expansion medium or hormonal treatment

  Raw, unfiltered fastq files obtained through RNA-seq of endometrial organoids from MRKH patients and controls. The dataset divides into three parts, depending on the growth conditions of the organoids, ie expansion medium or treated with hormones. Each sample consists of two paired-end fastq files.

  Dataset EGAD00001008453

• Whole genome sequence of monozygotic twins

  We generated whole genome sequence data from a family of monozygotic twins. DNA was obtained from blood, buccal epithelial cells, placenta, and umbilical cords of monozygotic twins. DNA from the parents were also obtained. Libraries were generated using Truseq-PCR free, Truseq nano, and NEBnext Ultra II depending on the availability of DNA. Data was generated on Illumina NovaSeq platform. Raw sequence data was aligned to the human reference genome GRCh38 using bwa mem aligner.

  Dataset EGAD00001008677

• Comparison of the antiviral immune response between individuals of Indian and European origin

  We purified peripheral blood mononuclear cells from individuals living in India (N=10) and the Netherlands (N=10) at baseline and 10-12 weeks after BCG vaccination. We compared chromatin accessibility between the two populations at baseline, as well as gene transcription profiles and cytokine production capacities upon viral stimulation with influenza and SARS-CoV-2

  Dataset EGAD00001009079

• WES of germline, nevi, primary and metastatic Cutaneous Melanoma from patient 009 in CASVAC-0401 trial

  Samples: primary cutaneous melanoma (CM) non-associated or distal nevus (A); adjacent or CM-associated nevus (B); Primary-CM (C); and Lymph-Node Metastasis (LN-mts) (D). Whole-exome sequencing (WES) was performed in DNA extracted from the different samples (A-D) paired with the germline reference (G), processed with the Agilent SureSelect All Exon Human V5 Library in an Illumina Hiseq 4000 PE101 platform.

  Dataset EGAD00001009083

• Paired RNA-Seq data from 17 samples of different tumors

  Paired RNA sequencing data (21 runs/ 17 samples) of different tumors. The samples were prepared using the Illumina TruSeq stranded mRNA Kit. The sequencing was done on Illumina HiSeq 4000.

  Dataset EGAD00001009706

• Synchronous patterning of hiPSC-derived CNS progenitors generates comprehensive axial spinal cord organoids (CASCOs) containing diverse motor neuron population

  Advancements in human induced pluripotent stem cell (hiPSC) culture have enabled the generation of spinal cord organoids (SCOs), though achieving distinct axial identities in spinal motor neurons (spMNs) along the rostro-caudal (RC) axis remains a challenge. By optimizing the timing and sequence of patterning factors, we developed a mixed stem cell model of rostral neural stem cells (NSCs) and caudal neuromesodermal progenitors (NMPs) to generate SCOs with enhanced spMN heterogeneity, including a wide range of axial identities and benchmarked this against commonly used protocols. Our approach, termed CASO (Comprehensive Axial Spinal Organoids), also incorporates endothelial networks and skeletal muscle to improve organoid complexity and health, offering a novel method to study spMN axial specification and model neurodegenerative diseases.

  Study EGAS50000000891

• RNA-seq of cultured human hematopoietic stem and progenitor cells from umblical cord blood in cytokine-rich ex vivo culture conditions following sphingolipid modulation

  To elucidate the biological pathways altered by sphingolipid modulation with N-(4-hydroxyphenyl) retinamide (4HPR) treatment in human HSPC that may contribute to the restraint in proliferation while promoting persistence of HSC self-renewal as well as determine the mechanism of synergy in enhancement of HSC self-renewal with CB CD34+ agonists UM171 and StemRegenin 1 (SR1), we performed RNA-sequencing (RNA-Seq) of 3 pools of lin-CB cells following 2 or 4 days with DMSO, 4HPR, UM171+SR1 or 3-Factor (4HPR+UM171+SR1). We identified modulation of sphingolipid metabolism regulates self-renewal through activating coordinated stress pathways that coalesce on endoplasmic reticulum stress and autophagy programs.

  Study EGAS00001003756

• Clinical activity and molecular correlates of response to atezolizumab alone or in combination with bevacizumab versus sunitinib in renal cell carcinoma

  We examined pre-treatment tumors from participants of the IMmotion150 trial. Biomarker analyses indicate that high angiogenesis gene expression was associated with improved PFS within the sunitinib arm, and high T-effector/IFNγ response (Teff) gene expression with longer PFS in atezolizumab + bevacizumab vs sunitinib patients. In high Teff tumors, concomitant high myeloid inflammation was associated with worse PFS in the atezolizumab monotherapy arm; adding bevacizumab to atezolizumab in this subgroup improved PFS vs atezolizumab. Molecular profiles suggest that prediction of outcomes with VEGF inhibitors and immunotherapy may be possible in mRCC, and bevacizumab may overcome myeloid inflammation-associated atezolizumab resistance.

  Study EGAS00001002928

• Combined – whole blood and skin fibroblasts - transcriptomic analysis in Psoriatic arthritis.

  Whole blood RNA sequencing was performed longitudinally in 27 subjects with PsA at the beginning, one month and six months after treatment and response to therapy was defined at 6 months. As control groups 7 healthy individuals and 9 subjects with rheumatoid arthritis were recruited combined with public RNA-sequencing datasets from patients with psoriasis and systemic lupus erythematous. Differential expression analysis and weighted gene co-expression network analysis were performed to identify gene expression signatures, while deconvolution and flow cytometry to characterize the peripheral blood immune cell profile. RNA sequencing of skin fibroblasts was performed in a subset of affected (n=3) and healthy individuals (n=3) combined with CellChat to identify the blood-skin fibroblasts interaction network.

  Study EGAS00001006288

• WES-based association study of cefaclor-induced anaphylaxis

  This study investigates the genetic factors associated with cefaclor-induced anaphylaxis using whole-exome sequencing (WES).

  Study EGAS50000001163

• LUMC Department Biomedical Data Sciences, Osteoarthritis group

  Committee to control single nucleus multiomics data generated within the project Single Cell Microgel embedded iPS-cells to map molecular variability of cell differentiation using a systems biology approach (SCI-MAP) at the LUMC.

  Dac EGAC50000000644