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• A Phase 2 Study of Lamivudine in Patients with p53 Mutant Metastatic Colorectal Cancer

  This was an open-label, single-arm Phase II study of lamivudine in patients who had progressed on systemic therapy for advanced colorectal cancer with TP53 mutations. The phase II study had a two-stage design, with a target accrual of 20 evaluable patients for the first stage and a total of 32 patients for the whole study. The first 9 patients were treated with lamivudine at 150 mg PO bid continuously for 28-day cycles. Subsequent patients (10-32) received a higher dose of 600 mg PO bid continuously for 28-day cycles. Tumor assessments were performed every 8 weeks until documented disease progression by Response Evaluation Criteria in Solid Tumors (RECIST) or drug intolerance. Whole genome sequencing (WGS) and total RNA-seq were performed on pre- and post- treatment biopsies on this trial.

  Study phs002833

• BLUEPRINT release August 2015, ChIP-Seq for CD8-positive, alpha-beta T cell, on genome GRCh38

  ChIP-Seq data for 5 CD8-positive, alpha-beta T cell sample(s). 26 run(s), 26 experiment(s), 26 alignment(s) on human genome GRCh38. Part of BLUEPRINT release August 2015. Analysis documentation available at http://ftp.ebi.ac.uk/pub/databases/blueprint/releases/20150820/homo_sapiens/README_chipseq_analysis_ebi_20150820

  Dataset EGAD00001001513

• Anti-TIGIT antibody tiragolumab improves PD-L1 blockade via myeloid and Treg cells

  Tiragolumab, an anti-TIGIT antibody with an active IgG1/kappa Fc, demonstrated improved outcomes in the phase 2 CITYSCAPE trial (NCT03563716) when combined with atezolizumab (anti-PD-L1) versus atezolizumab alone1. However, there remains little consensus on the mechanism(s) of response with this combination2. We found that high baseline intratumoral macrophages and Tregs were associated with better outcomes in patients treated with atezolizumab plus tiragolumab but not with atezolizumab alone. Serum sample analysis revealed that macrophage activation was associated with clinical benefit in patients receiving the combination treatment. In mouse tumor models, tiragolumab surrogate antibodies inflamed tumor-associated macrophages, monocytes, and dendritic cells through Fc gamma receptors (FcɣR), in turn driving anti-tumor CD8+ T cells from an exhausted effector-like state to a more memory-like one. These results uncover a mechanism of action by which TIGIT checkpoint inhibitors can remodel immunosuppressive tumor microenvironments, and suggest that FcɣR engagement is an important consideration in anti-TIGIT antibody development.

  Study EGAS50000000251

• Immunoprotective mechanisms and microbiota interplay in Salmonella Typhi infection

  Vaccine development against Salmonella enterica serovar Typhi (S. Typhi) requires a better understanding of interaction between human host and the resident microbial consortia in gastrointestinal tract. Healthy adult volunteers received either Ty21a, M01ZH09 or placebo, and underwent challenges with wt S. Typhi. Stool samples were collected at the screening interview (Baseline 1), prior to the first vaccination visit (Baseline 2), during vaccination (Day -28 and -26 for placebo and M01ZH09 groups; Day -32, -30, -28, -26 for Ty21a group), prior to challenge with S. Typhi (Day 0), and after challenge (day 0 12h, day 1, day 3, day 7, and day 10). 16S rRNA and messenger RNA were extracted from stool and sequenced on the Illumina Miseq and HiSeq 2000 platforms, respectively.

  Study phs001521

• Botensilimab, an Fc-enhanced Anti-CTLA-4 Antibody, is Effective Against Tumors Poorly Responsive to Conventional Immunotherapy

  This study explores the genomic landscape associated with a novel Fc-engineered anti-CTLA-4 antibody (botensilimab) in advanced solid tumors. We seek to understand if enhancing the Fc-region affinity of anti-CTLA-4 antibodies can improve anti-tumor efficacy and expand clinical benefit to tumors poorly responsive to conventional immunotherapy. As part of an ongoing open-label, Phase 1, multicenter study, we conducted an exploratory sub-analysis of genomics data. The primary study evaluates the safety, tolerability, pharmacokinetics, and pharmacodynamics of botensilimab monotherapy and in combination with an anti-PD-1 antibody (balstilimab) in participants with advanced solid tumors. RNA from formalin-fixed paraffin-embedded (FFPE) tumor biopsies and matched normal blood samples were isolated and subjected to RNA-sequencing using the Personalis ImmunoID NeXT Platform. We demonstrated that anti-CTLA-4 engineered for enhanced FcγR affinity leverages FcγR-dependent mechanisms to potentiate T cell responsiveness, reduce intratumoral Tregs, and enhance antigen presenting cell activation. This genomic analysis contributes to our understanding of the molecular mechanisms underlying patient responses to Fc-engineered anti-CTLA-4 therapy and may inform future strategies to expand the clinical benefit of immune checkpoint blockade in cancer immunotherapy.

  Study phs003704

• Fgl2 Regulates FcγRIIB+ CD8+ T Cell Responses during Infection

  While the inhibitory receptor FcγRIIB has been shown to be upregulated on activated CD8+ T cells in both mice and humans, its impact on T cell fate during infection has not been fully elucidated. We identified an increase in FcγRIIB-expressing CD8+ T cells in COVID patients relative to healthy controls, and in mouse models of viral infection. Despite its well-known role as an Fc receptor, FcγRIIB also ligates the immunosuppressive cytokine Fgl2, resulting in CD8+ T cell apoptosis. Both chronic LCMV infection in mice and COVID in humans resulted in a significant increase in plasma Fgl2. Further, plasma Fgl2 was directly proportional to CD8+ T cell lymphopenia in COVID patients. To further understand the association of Fgl2 and CD8+ T cell lymphopenia following COVID infection, we assessed the transcriptomic profiles of PBMCs with high (≥ 9.153 ng/ml) vs low (defined as

  Study phs003870

• Single-cell RNA sequence analysis of iPS cell-derived cardiomyocytes treated with S-RBD-sfGFP or GFP

  To determine the transcriptional response in human cardiomyocytes treated with SARS-CoV-2 spike receptor-binding domain (S-RBD-sfGFP), human cardiomyocytes differentiated from induced pluripotent stem cells (iPSC-CMs) were replated on day 21 after differentiation and treated with S-RBD-sfGFP or control-GFP for 48 hours on day 26-28. iPSC-CMs were dissociated and the single cell suspension was analyzed by single cell RNA-sequence.

  Study JGAS000620

• Data Access Committee KCL FC

  Dac EGAC00001000386

• BLUEPRINT release August 2016, ChIP-Seq for band form neutrophil, on genome GRCh38

  ChIP-Seq data for 4 band form neutrophil sample(s). 26 run(s), 23 experiment(s), 23 analysis(s) on human genome GRCh38. Part of BLUEPRINT release August 2016. Analysis documentation available at http://ftp.ebi.ac.uk/pub/databases/blueprint/releases/20160816/homo_sapiens/README_chipseq_analysis_ebi_20160816

  Dataset EGAD00001002454

• MCF10A 12h IL6 classical signaling

  Gene expression after cell culture, 12h IL6+sgp130-Fc stimulated

  Dataset EGAD00010001970

• MCF10A 24h IL6 classical signaling

  Gene expression after cell culture, 24h IL6+sgp130-Fc stimulated

  Dataset EGAD00010001963

• Characterization of a human iPSC-derived endocrine pancreas model

  Directed differentiation of stem cells offers a scalable solution to the need for human cell models recapitulating islet biology and T2D pathogenesis. We profiled mRNA expression at six stages of an induced pluripotent stem cell (iPSC) model of endocrine pancreas development from two donors, and characterized the distinct transcriptomic profiles associated with each stage. Established regulators of endodermal lineage commitment, such as SOX17 (log2 fold change [FC] compared to iPSCs=14.2, p-value=4.9x10-5) and the pancreatic agenesis gene GATA6 (log2 FC=12.1, p-value=8.6x10-5), showed transcriptional variation consistent with their known developmental roles. However, these analyses highlighted many other genes with stage-specific expression patterns, some of which may be novel drivers or markers of islet development. For example, the leptin receptor gene, LEPR, was most highly expressed in published data from in vivo-matured cells compared to our endocrine pancreas-like cells (log2 FC=5.5, p-value=2.0x10-12), suggesting a role for the leptin pathway in the maturation process. Endocrine pancreas-like cells showed significant stage-selective expression of adult islet genes, including INS, ABCC8, and GLP1R, and enrichment of relevant GO-terms (e.g. "insulin secretion"; odds ratio=4.2, p-value=1.9x10-3): however, principal component analysis indicated that in vitro-differentiated cells were more immature than adult islets. Integration of the stage-specific expression information with genetic data from T2D genome-wide association studies revealed that 46 of 82 T2D-associated loci harbor genes present in at least one developmental stage, facilitating refinement of potential effector transcripts. Together, these data show that expression profiling in an iPSC islet development model can further understanding of islet biology and T2D pathogenesis.

  Study EGAS00001001803

• Evaluation Study of Congestive Heart Failure and Pulmonary Artery Catheterization Effectiveness (ESCAPE-BioLINCC)

  Accessing Data Please refer to “Authorized Access” below regarding accessing data through the BioData Catalyst ecosystem. The data from this accession is not available for download through dbGaP. Objectives To test whether pulmonary artery catheter use was safe and could improve clinical outcomes in participants hospitalized with recurrent heart failure. Background Pulmonary artery catheters have been used to guide adjustment of therapy in multiple settings, but recent studies have raised concern that pulmonary artery catheters may lead to increased mortality in hospitalized participants. Participants A total of 433 participants at 26 sites were enrolled, and randomly assigned to receive therapy guided by clinical assessment and the pulmonary artery catheter or clinical assessment alone. Patients with acute decompensation in which the attending heart failure physician considered pulmonary artery catheterization (PAC) was required or likely to be required within the next 24 hours were entered into a PAC registry. A total of 439 patients were added to the registry. Conclusions Therapy to reduce volume overload during hospitalization for heart failure led to marked improvement in signs and symptoms of elevated filling pressures, with or without the pulmonary artery catheter. Addition of the pulmonary artery catheter to careful clinical assessment did not impact overall mortality and hospitalization. Future trials should test noninvasive assessments with specific treatment strategies that could be used to better tailor therapy for both survival time and survival quality as valued by participants. (Binanay, C. et al., JAMA, 2005)

  Study phs003782

• Expression profiling of a human endocrine pancreas iPSC model

  Directed differentiation of stem cells offers a scalable solution to the need for human cell models recapitulating islet biology and T2D pathogenesis. We profiled mRNA expression at six stages of an induced pluripotent stem cell (iPSC) model of endocrine pancreas development from two donors, and characterized the distinct transcriptomic profiles associated with each stage. Established regulators of endodermal lineage commitment, such as SOX17 (log2 fold change [FC] compared to iPSCs=14.2, p-value=4.9x10-5) and the pancreatic agenesis gene GATA6 (log2 FC=12.1, p-value=8.6x10-5), showed transcriptional variation consistent with their known developmental roles. However, these analyses highlighted many other genes with stage-specific expression patterns, some of which may be novel drivers or markers of islet development. For example, the leptin receptor gene, LEPR, was most highly expressed in published data from in vivo-matured cells compared to the endocrine pancreas-like cells (log2 FC=5.5, p-value=2.0x10-12), suggesting a role for the leptin pathway in the maturation process. Endocrine pancreas-like cells showed significant stage-selective expression of adult islet genes, including INS, ABCC8, and GLP1R, and enrichment of relevant GO-terms (e.g. “insulin secretion”; odds ratio=4.2, p-value=1.9x10-3): however, principal component analysis indicated that in vitro-differentiated cells were more immature than adult islets. Integration of the stage-specific expression information with genetic data from T2D genome-wide association studies revealed that 46 of 82 T2D-associated loci harbor genes present in at least one developmental stage, facilitating refinement of potential effector transcripts. Together, these data show that expression profiling in an iPSC islet development model can further understanding of islet biology and T2D pathogenesis.

  Dataset EGAD00001002148

• Ribo-depleted RNA-sequencing of II.3, III.1, and III.3

  This datasets contains the Ribo-depleted RNA-sequencing of patients II.3, III.1, and III.3. Libraries were sequenced to a minimum depth of 195 million read pairs (2x75nts) on an Illumina NextSeq500 Midoutput FC.

  Dataset EGAD50000002364

• PATL2 is a key actor of oocyte maturation whose invalidation causes infertility in women and mice

  The genetic causes of oocyte meiotic deficiency (OMD), a form of primary infertility characterised by the production of immature oocytes, remain largely unexplored. Using whole exome sequencing, we found that 26% of a cohort of 23 subjects with OMD harboured the same homozygous nonsense pathogenic mutation in PATL2, a gene encoding a putative RNA-binding protein. Using Patl2 knockout mice, we confirmed that PATL2 deficiency disturbs oocyte maturation, since oocytes and zygotes exhibit morphological and developmental defects respectively. PATL2's amphibian orthologue is involved in the regulation of oocyte mRNA as a partner of CPEB. However, Patl2's expression profile throughout oocyte development in mice, alongside colocalisation experiments with Cpeb1, Msy2 and Ddx6 (three oocyte RNA-regulators) suggest an original role for Patl2 in Mammals. Accordingly, transcriptomic analysis of oocytes from WT and Patl2-/- animals demonstrated that in the absence of Patl2, expression levels of a select number of highly relevant genes involved in oocyte maturation and early embryonic development are deregulated. In conclusion, PATL2 is a novel actor of mammalian oocyte maturation whose invalidation causes OMD in humans.

  Study EGAS00001002903

• IMCISION DNAseq

  Standard-of-care (SOC) surgery for locoregionally advanced head and neck squamous cell carcinoma (HNSCC) is intensive and results in 30‒50% five-year overall survival. Anti-PD1 immune checkpoint blockade (ICB) durably improves survival rates in recurrent/metastatic HNSCC. We report on the non-randomized phase Ib/IIa IMCISION trial (NCT03003637) of 32 HNSCC patients treated with two doses neoadjuvant nivolumab (NIVO MONO, n=6, phase Ib arm A) or two doses of nivolumab plus a single dose of ipilimumab (COMBO, n=26, 6 in phase Ib arm B and 20 in phase IIa) prior to surgery and, if indicated, adjuvant radiotherapy. Neoadjuvant ICB was feasible in all phase Ib patients, meeting the phase Ib primary feasibility endpoint. One phase IIa patient had progressive disease precluding surgery. Primary tumor pathological response (phase IIa primary endpoint), defined as the % change in viable tumor cells from baseline biopsy to on-treatment resection, was evaluable in 29 patients. . We observed a major pathological response (MPR, 90‒100% response) in 8/23 (35%) evaluable COMBO and 1/6 (17%) NIVO MONO patients. None of the patients with MPR after NIVO MONO or COMBO developed a tumor relapse after 24.0 months median follow-up. FDG-PET-based total lesion glycolysis identified MPR patients prior to surgery. A baseline AID/APOBEC-associated mutational profile and an on-treatment decrease in hypoxia signature expression were observed in MPR patients. Our data indicate that neoadjuvant NIVO MONO and COMBO are safe in HNSCC, and that particularly COMBO ICB shows encouraging effectivity. IMCISION provides rationales for future HNSCC trials aiming to pre-operatively select patients with a likely MPR after neoadjuvant ICB for de-escalation of SOC.

  Study EGAS00001005466

• Whole exome sequencing of endometriod ovarian cancer tumours

  Whole Exome sequencing data of tumour samples for 112 patients with endometrioid ovarian carcinoma in FASTQ format. Data was derived as summarized below: Library Preparation: Libraries were prepared from each DNA sample using the Illumina TruSeq Exome Library Prep kit (#FC-150-1002) according to the provided protocol using modifications for working with FFPE sourced material. Libraries were quantified using the Qubit 2.0 Fluorometer and the Qubit DNA HS assay (#Q32854) and the size distribution of fragments was assessed using the Agilent Bioanalyser with the DNA HS Kit (#5067-4626). Library QC: Exome-captured sequencing library pools were quantified using the Qubit 2.0 Fluorometer and the Qubit DNA HS assay (#Q32854) and the size distribution of fragments was assessed using the Agilent Bioanalyser with the DNA HS Kit (#5067-4626). Fragment size and quantity measurements were used to calculate molarity for each library pool. Sequencing: Sequencing was performed using the NextSeq 500/550 High-Output v2 (150 cycle) Kit (# FC-404-2002) on the NextSeq 550 platform (Illumina Inc, #SY-415-1002).

  Dataset EGAD00001006389

• Efficacy of a Therapeutic Treatment Trial in Angelman Syndrome

  This study has been designed to evaluate the possible therapeutic benefits of L-5-methyltetrahydrofolate (Metafolin), vitamin B12, creatine and betaine in children with Angelman Syndrome (AS). This study is based on the hypotheses 1) that dietary manipulation may increase global DNA methylation; 2) that increased methylation of the paternal chromosome in AS participants may increase expression of the Angelman gene causing clinical benefit; and 3) that dietary interventions with Metafolin in conjunction with creatine, betaine, and vitamin B12 would represent little risk, but some chance for benefit. The dietary regimen is felt to be quite benign and safe. The clinical response will be measured by recording: changes in seizure activity, changes in communication skills, changes in developmental skills and changes in behavioral patterns as indicated by formal developmental assessments and clinical evaluations. We will assess the progress of the participants by monitoring their changes from baseline throughout their participation in the study and measure their improvement in particular in the developmental parameters. As a secondary aim, we plan to measure the biochemical response to these compounds by obtaining levels of homocysteine, methionine, S-adenosyl-methionine (SAM), and S-adenosyl-homocysteine (SAH). The molecular response will be measured by global DNA methylation analysis. As an exploratory aim, we hope to use control data we have previously obtained from a double blind placebo-controlled trial done in the past using betaine and folic acid to compare the development of those children who have and those who have not received medications. More specifically, we wish to compare differences in the rate of development for those children who have never received study medications (from the first trial) with those who have received medications from the present trial. Developmental parameters used in the previous trial will be consistent with those used in the present trial in order to permit these comparisons. The previous trial was conducted at Baylor College of Medicine, Rady San Diego Children's Hospital and Boston Children's Hospital whereas a group of AS participants received folic acid and betaine or placebo in a randomized double-blind basis. All the participants for the study will include patients who have a documented molecular diagnosis of AS. The participants will be seen at Baylor College of Medicine, Rady Children's Hospital of San Diego, Boston Children's Hospital and the Greenwood Genetics Center at 0 months and at 12 months for follow-up. Clinical and relevant historical data will be collected during the clinical visit and examination and also by reviewing medical and laboratory records. This information will then be entered into a HIPAA compliant clinical research database.

  Study phs000701

• Colon cancer ctDNA

  Samples prepared using Safe-SeqS technology. All samples ran on an Illumina MiSeq instrument. Fastq files for read 1 and the index read present (R and I respectively).

  Dataset EGAD00001003579

• A Dose Escalation Study of Efmarodocokin Alfa (UTTR1147A) in Healthy Volunteers and Patients with Ulcerative Colitis

  Background: The interleukin-22 cytokine (IL-22) has demonstrated efficacy in nonclinical colitis models with a non-immunosuppressive mechanism-of-action. Efmarodocokin alfa (UTTR1147A) is a fusion protein agonist that links IL-22 to the crystallizable fragment (Fc) of human immunoglobulin (IgG4) for improved pharmacokinetic characteristics, but with a mutation to minimize Fc effector functions. Methods: This randomized, phase 1b study evaluated the safety, tolerability, pharmacokinetics, and pharmacodynamics of repeat intravenous dosing of efmarodocokin alfa in healthy volunteers (HVs; n=32) and patients with ulcerative colitis (UC; n=24) at 30–90 µg/kg doses given biweekly (Q2W) or monthly (Q4W) (6:2 active:placebo per cohort). Results: The most common adverse events (AEs) were on-target dermatological effects (dry skin, erythema, and pruritus) that were reversible. Dose-limiting non-serious dermatological AEs (severe dry skin, erythema, exfoliation, and discomfort) were seen in two HVs and one patient at 90 ug/kg Q2W. Pharmacokinetics were generally dose-proportional across the dose levels tested, but patients demonstrated lower drug exposures relative to HVs at the same dose. IL-22 serum biomarkers and IL-22 responsive genes in colon biopsies were induced with active treatment. Patients demonstrated changes in microbiota composition following active treatment, thereby reversing baseline dysbiosis. Clinical response was observed in 7/18 active- and 1/6 placebo-treated patients; clinical remission was observed in 5/18 active- and 0/6 placebo-treated patients.

  Study EGAS00001006172

• Viral evasion Strategy for Generating Hypoimmunogenic hiPSC Lines

  Mismatches in HLA haplotypes between donors and recipients significantly increase the risk of graft failure due to immune rejection. To address these limitations, we introduced a cytomegalovirus-derived US2 encoding sequence into the AAVS1 safe-harbor locus of a human induced pluripotent stem cell (hiPSC) line. US2 expression in iPSC abolished HLA-A2 alloreactive T-cell activation without increasing NK cell degranulation, indicating preserved inhibitory signaling.

  Study EGAS50000001618

• Characterizing the cell-free transcriptome in a humanized DLBCL patient-derived tumor xenograft model for RNA-based liquid biopsy in a preclinical setting

  This study explores the cell-free transcriptome in a humanized DLBCL patient-derived tumor xenograft (PDTX) model. Blood plasma samples (n=171) derived from a DLBCL PDTX model including 27 humanized (HIS) PDTX, 8 HIS non-PDTX and 21 non-HIS PDTX NOD-scid IL2Rgnull mice were collected during humanization, xenografting, treatment, and sacrifice. The mice were treated with either R-CHOP, huCD20-Fc-AFN-CHOP, or phosphate-buffered saline (PBS). RNA was extracted using the miRNeasy serum/plasma kit and sequenced on the NovaSeq 6000 platform using the SMARTer Stranded Total RNA-seq pico v3 kit.

  Study EGAS50000000566

• High titers and low fucosylation of early phase anti-SARS-CoV-2 IgG promote hyper-inflammation by alveolar macrophages

  We show that early phase anti-Spike IgG in serum of critically ill COVID-19 patients induces hyper-inflammatory responses by human alveolar macrophages. We identified that this excessive inflammatory response is dependent on two antibody features that are specific for severe COVID-19. First, inflammation is driven by high titers of anti-Spike IgG, a hallmark of severe disease. Second, we found that anti-Spike IgG from severely ill patients is intrinsically more pro-inflammatory because of different glycosylation of the Fc tail, particularly by low fucosylation. This dataset is linked with the following ArrayExpress Experiment: E-MTAB-10431 - 2020_COVID19_FCGR_MIL10_IgGfucosylation

  Study EGAS00001005206

• Exome Sequencing of Esophageal Adenocarcinoma

  The incidence of esophageal adenocarcinoma (EAC) has risen 600% over the last 30 years. When coupled to the five-year survival rate of only 15% for this disease, identification of new therapeutic targets for EAC is of great importance. Here, we analyze the mutational spectra identified from the whole genome sequencing of 16 EACs and complete exome sequencing of 149 EAC tumors and matched germline samples. We identify a novel mutation signature marked by high prevalence of A to C transversions at AA*(N) trinucleotides. Notably, the development of EAC is preceded by pathologic intestinal metaplasia of the lower esophagus, Barrett's esophagus, itself a response to injury from gastric-esophageal reflux disease (GERD). Thus, we hypothesize to represent these AA*(N) mutations to a novel signature of GERD-induced mutagenesis. Analysis of the exome data identified 26 genes subject to statistically significant recurrent mutation. Of these 26 genes, only TP53, CDKN2A, SMAD4, and PIK3CA had been previously implicated in EAC. Novel mutations include those targeting chromatin modifying factors and novel candidate contributors to EAC: SPG20, TLR4, ELMO1 and DOCK2. Of these, ELMO1 and DOCK2 are notably direct dimerization partners that act to activate Rac1 to enhance cellular invasiveness, thus generating new hypotheses about the potential for the Rac1 pathway to be a novel target for therapy of EAC. "Reprinted from 'Unraveling the mutational complexity of esophageal adenocarcinoma', with permission from Nature Genetics."

  Study phs000598

• GEDI: A Developmental Model of Gene-Environment Interplay in SUDs: Combined Genotype Dataset from the "Great Smoky Mountains Study" and the "Caring for Children in the Community Study".

  1. Great Smoky Mountains Study (GSMS; Costello et al. 1996, 1997) Three cohorts of boys and girls, aged 9, 11, and 13 years at intake in 1993, were selected from a rural population of some 20,000 children using a household equal probability design. A two-phase procedure was used for White and African-American youth to increase power by oversampling children at risk for psychiatric and SUDs. Parents (usually mothers) of the first stage random population sample completed a questionnaire about their child's behavioral problems. Of 4,195 subjects selected, 95% (N=3,896) of parents completed the screen. All children scoring above a predetermined threshold (the top 25% of the total scores), plus a 10% random sample of the remaining 75%, were recruited for detailed interviews. Results can be back-weighted to population levels for analyses. Half of the sample consists of females, and 6% are African Americans, reflecting the population of the study area. The interviewed sample of white and African-American subjects was 1,070 (80% of those recruited). American Indian youth were oversampled (100%) because they are an understudied group known to be at high risk for stressful events, substance disorders, and mood disorders. Of 431 age-eligible children, 350 (81% boys, 49% girls) participated. Thus, the size of total GSMS sample is 1,070 + 350 = 1,420. Data collection is complete for ages 9-26, and age 30 interviews are in progress. By age 26 a total of 9,858 interviews had been completed; the average number of interviews per subject was seven, and by age 26, 97.3% completed two or more interviews. 2. The Caring for Children in the Community Study (CCC; Angold et al., 2002) This representative study of psychiatric illness and service use in African-American and White youth took place in four rural counties in the southeastern USA. The two-stage sampling design and methods are similar to those used in the GSMS. Of 4,500 youth randomly selected from the 17,117 9- to 17-year-olds in the public school's database, 3,613 (80.0%) were successfully contacted and agreed to complete the behavioral screen. Of the 1,302 selected to participate in the study, 920 (70.7%) interviews were completed. Because CCC was also the only study in GEDI to contain more than a very few African-American participants, these were omitted from the multi-site analyses. Reprinted with permission from Cambridge University Press from Costello et al., 2013: PMID: 23461817 References: Costello et al., 1996: PMID: 8956679 Costello et al., 1997: PMID: 9184514 Angold et al., 2002: PMID: 12365876

  Study phs000852

• CancerSEEK ctDNA FASTQ files

  Sequencing data from 1,005 cancer patients and 812 healthy controls. All samples prepared using Safe-SeqS technology and sequenced on an Illumina MiSeq and/or HiSeq instrument. Paired FASTQ files for correspond to read 1 and the index read present (R and I respectively).

  Dataset EGAD00001003931

• dataset1

  Contains test sample 1-26

  Dataset EGAD00010002041

• High-resolution profile of neoantigen-specific TCR activation links moderate stimulation to increased resilience of engineered TCR-T cells

  Neoantigen-specific T cell receptors (neoTCRs) promise safe, personalized anti-tumor immunotherapy. Previously, we identified diverse neoTCRs restricted to different neoantigens in a melanoma patient. In this work, we now combined single-cell TCR- and RNA-sequencing after neoantigen-specific restimulation of peripheral blood-derived CD8+ T cells of this patient. We detected novel neoTCRs with specificity to the previously detected neoantigens and observe a heterogeneous spectrum of TCR-intrinsic activation patterns in response to a shared neoepitope ranging from previously detected higher frequent neoTCRs with moderate activation to rare ones with initially stronger activation.

  Study EGAS50000000600

• DAC-2020-03-26-Lemola (DAC-039))

  DAC-2020-03-26-Lemola (DAC-039)), raw data in EGA, metadata in Harvard Dataverse

  Dataset EGAD50000000897

• T cell transcriptional gradient

  There are two datasets: 1. scRNA-seq of human cutaneous immune cells from psoriasis patients. These include pre- and post-Tildrakizumab treated patients and come in a BAM file format. 19006FL-25-01 19006FL-38-01 19006FL-32-01-03 19006FL-33-01 19006FL-28-01-05 19006FL-35-01-01 2. RNA-seq of ZFP36L2 CRISPIR deleted Human T cells are FASTQ files. 19006XR-30-05 19006XR-30-04 19006XR-30-02 19006XR-30-01 19006XR-26-05 19006XR-26-04 19006XR-26-02 19006XR-26-01 19006R-22-04 19006R-22-08 19006R-22-05 19006R-22-01

  Dataset EGAD00001009677

• Single-cell transcriptomics identifies pathogenic T-helper 17.1 cells and pro-inflammatory monocytes in ICI-related pneumonitis

  ICI-pneumonitis is a frequent serious adverse event of cancer immunotherapy hinging on a cell-mediated immune response, though the exact pathophysiology is currently unknown. Using single-cell transcriptomics, an enrichment of pathogenic (TBX21, RORC, IFNG, IL17A, CSF2 expressing) T-helper 17.1 cells and pro-inflammatory (TNF, IL1B, IL6, IL23A expressing) monocytes was identified in ICI-pneumonitis bronchoalveolar lavage fluid, putatively engaging in a feedforward inflammatory loop. This finding yields several novel therapeutic targets for the treatment of ICI-pneumonitis. Most notably repurposing anti-IL-23 merits further research as a potential efficacious and safe treatment for ICI-pneumonitis.

  Study EGAS00001006762

• Pediatric Whole Genome Sequencing Diagnostic Utility

  The standard of care for first-tier clinical investigation of the etiology of congenital malformations and neurodevelopmental disorders is chromosome microarray analysis (CMA) for copy number variations (CNVs), often followed by gene(s)-specific sequencing searching for smaller insertion-deletions (indels) and single nucleotide variant (SNV) mutations. We compared diagnostic rate of WGS to CMA and targeted gene testing of 100 patients referred to The Hospital for Sick Children Genetics clinic in 2014. WGS identified genetic variants meeting clinical diagnostic criteria in 34% of cases, representing a 4-fold increase in diagnostic rate over CMA (8%) (p-value = 1.42e-05) alone and >2-fold increase in CMA plus targeted gene sequencing (13%) (p-value = 0.0009). WGS identified all rare clinically significant CNVs that were detected by CMA. In an additional 26 patients, WGS revealed indel and missense mutations presenting in a dominant (63%) or a recessive (37%) manner. We found four subjects with mutations in at least two genes associated with distinct genetic disorders, including two cases harboring a pathogenic CNV and SNV. When considering medically actionable secondary findings in addition to primary WGS findings, 38% of patients would benefit from genetic counselling.

  Study EGAS00001001623

• WGS of Multiple Myeloma/MGUS/SMM cases (germline) - VCF files (SNPs)

  WGS - PCR-free library preparation (whole blood gDNA), paired-end (2x100bp) sequencing on DNBseq sequencing platform (BGI) Number of samples: 26

  Dataset EGAD50000001800

• scRNA-seq analysis of HGSC tumors, including immune TME, before and after NACT

  Gene expression profiles of single cells from 26 tumor and ascites samples samples from 17 patients

  Dataset EGAD50000000862

• H3Africa H3AChipDesign TrypanoGEN1

  26 samples from Cameroon generated for the H3Africa Chip Design Study. The dataset includes BAM, FASTQ and decompressed gVCF files.

  Dataset EGAD00001004393

• ATAC-seq

  ATAC-seq data for 26 CLL samples (7 controls, 19 tumor) of the CancerEpiSys-PRECiSe project.

  Dataset EGAD00001005967

• Phenotype information

  This study explores the cell-free transcriptome in a humanized DLBCL patient-derived tumor xenograft (PDTX) model. Blood plasma samples (n=171) derived from a DLBCL PDTX model in-cluding 27 humanized (HIS) PDTX, 8 HIS non-PDTX and 21 non-HIS PDTX non-obese diabetic (NOD)-scid IL2Rgnull (NSG) mice were collected during humanization, xenografting, treatment, and sacrifice. The mice were treated with either rituximab, cyclophosphamide, doxorubicin, vincris-tine, and prednisone (R-CHOP), CD20-targeted human IFNα2-based AcTaferon combined with CHOP (huCD20-Fc-AFN-CHOP), or phosphate-buffered saline (PBS). RNA was extracted using the miRNeasy serum/plasma kit and sequenced on the NovaSeq 6000 platform using the using the SMARTer Stranded Total RNA-Seq Kit v3.

  Dataset EGAD50000000806

• RNA-seq of tumor samples from clear cell renal cell carcinoma patients included in the Translational Program of the NIVOREN GETUG-AFU-26 trial.

  DAC for RNA-seq of tumor samples from clear cell renal cell carcinoma patients included in the Translational Program of the NIVOREN GETUG-AFU-26 trial.

  Dac EGAC50000000627

• Refractory Classic Hodgkins Lymphoma (cHL) sWGS

  Associated with the study: Blood-based Monitoring of Relapsed/Refractory Hodgkin Lymphoma Patients Predict Responses to Anti-PD-1 Treatment. 26 ctDNA Samples from 4 patients followed longitudinally. sWGS performed for copy number aberration (CNA) analysis.

  Dataset EGAD50000001163

• Chemotherapy induces myeloid-driven spatial T-cell exhaustion in ovarian cancer

  Gene expression profiles of single cells from 26 chemo-naïve and IDS tumor tissue and ascites samples from 17 HGSC patients

  Study EGAS50000000607

• dataset1

  Contains 14 control samples and 26 case samples.

  Dataset EGAD00001008576

• Sequencing files for "Transcriptional Mechanisms of Resistance to Anti-PD-1 Therapy"

  Files from whole exome sequencing of 26 tumors and two matched normals from one melanoma patient. The 26 tumors include the untreated primary, cutaneous metastases and distant metastases to internal organs.

  Dataset EGAD00001003200

• Non-coding mutations reveal cancer driver cistromes in luminal breast cancer

  A dataset of ER+PR+ breast tumor samples that were analyzed in order to identify mutation enrichment in cis-regulatory elements and cistrome. The repository includes sequencing data from 88 patients. 26/88 were sequenced using ATAC-seq

  Dataset EGAD00001007650

• Multi-omics datasets (WES, RNA-seq) of mesothelioma MIST2 study, a phase II CDK4/6 (abemaciclib) clinical trial

  This study comprises 26 mesothelioma patients with whole exome and RNA sequencing, to to assess potential sensitivity to CDK4/6 inhibition in p16ink4A-negative mesothelioma.

  Study EGAS50000001823

• Long-read data (PacBio)

  The goal of this project was to perform long-read RNA sequencing (LR-seq, PacBio) in combination with short-read RNA-seq for systematic characterization of the isoform diversity in primary breast tumor samples. We sequenced the full-length transcriptomes of 26 breast tumors and 4 normal breast samples.

  Dataset EGAD00001006597

• Drug Perturbation of Primary Lymphoma Patient Samples and RNA Sequencing

  This submission contains 3'-end-based shallow-depth RNA sequencing data from 108 patients with chronic lymphocytic leukemia and 8 patients with lymphoma. Each primary patient sample was treated in vitro with DMSO as a control and with up to ten small-molecule drugs (ibrutinib, duvelisib, everolimus, trametinib, nutlin-3a, I-BET762, MK2206, selinexor, compound 26, and a combination of ibrutinib and compound 26). The samples were sequenced after 48 hours. The total data set consists of 1476 RNA sequencing samples from 6 batches (pilot, batch 1, batch 1 replicate, batch 2, batch 3, batch 4).

  Study EGAS50000001500

• Lymphoma_primary_patient_drug_perturbed_RNASeq_samples

  3'-end low-depth RNA sequencing data from 108 patients with chronic lymphocytic leukemia and 8 patients with lymphoma. Each primary patient sample was treated in vitro with DMSO as a control and with up to ten small-molecule inhibitors (ibrutinib, duvelisib, everolimus, trametinib, nutlin-3a, I-BET-762, MK2206, selinexor, compound 26, and a combination of ibrutinib and compound 26). Sequencing was performed on the Illumina HiSeq4000. The dataset contains FASTQ files.

  Dac EGAC50000000578

• scMultiome (snRNA + snATAC) data of 26 regionally sampled GBM tissue from 6 patients

  This dataset contains snRNA-seq data of 26 regionally sampled GBM tissue (peritumoral region, tumor edge, and tumor core). Regionally sampled GBM patient tissue was dissociated and nuclei were processed unsorted or by sorting with 7AAD to remove debris and dead cells. Single-nuclei suspension was prepared following the nuclei isolation protocol Single Cell Multiome ATAC + Gene Expression Sequencing protocol using Chromium Nuclei Isolation Kit. Single-nuclei suspension was prepared following the nuclei isolation protocol Single Cell Multiome ATAC + Gene Expression Sequencing protocol using Chromium Nuclei Isolation Kit, nuclei were barcoded and RNA and ATAC libraries were constructed, allowing for simultaneous capture of transcriptome and epigenome from the same cells.

  Dataset EGAD50000001838

• Exome-sequencing of human B cell lymphoma cell lines

  26 cell lines derived from human Diffuse Large B Cell lymphomas (DLBCL) or Burkit Lymphomas (BL) were subjected to whole exome sequencing. Exome capture was carried out using the SeqCap EZ Exome Library 2.0 kit (Roche/Nimblegen) and 100 bp single-read sequencing was performed on a HiSeq2500 (Illumina). 82% of the coding region was covered at least 30x.

  Dataset EGAD00001002262