12501 results for ""non-traditional+communal+storytelling+approach"+novel+segment+noted+in+critical+commentary"

in 21.36 milliseconds.

• PanCurX Translational Research Initiative - RNA-Seq mapped and unmapped reads

  Integration of Genomic and Transcriptional Features in Pancreatic Cancer Reveals Increased Cell Cycle Progression in Metastases - RNA-Seq mapped and unmapped reads

  Dataset EGAD00001004548

• Whole exome sequencing and target gene sequencing of ESCC cases and healthy controls from Henan high-risk region

  In total, 186 FH+ ESCC cases were sequenced using whole-exome sequencing, then 1935 ESCC cases and 1186 geographically-matched healthy controls were sequenced using 7 Mb custom designed Roche SeqCap kit which targeted about 600 genes. The libraries were constructed and then sequenced in Illumina platform.

  Dataset EGAD00001004556

• Repeated clinical malaria episodes are associated with modification of the immune system in children. (2019-01-17)

  Repeated clinical malaria episodes are associated with modification of the immune system in children.This data is part of a pre-publication release. For information on the proper use of pre-publication data shared by the Wellcome Trust Sanger Institute (including details of any publication moratoria), please see http://www.sanger.ac.uk/datasharing/. . This dataset contains all the data available for this study on 2019-01-17.

  Dataset EGAD00001004570

• STAMPEED: Whole Genome Association Analysis of Hematopoietic Cell Transplant (HCT) Outcomes

  This retrospective cohort study was designed to identify single nucleotide polymorphisms (SNPs) that are associated with complications after allogeneic hematopoietic cell transplantation (HCT). Validated discoveries provide information to improve risk assessment, counseling and treatment planning and to direct future mechanistic studies of the genes and pathways that influence outcomes, thereby providing insight and rationale for new targeted therapies. The study was conducted with the use of 3 different approaches. (1) We used GWAS discovery and replication analyses to identify SNPs variants associated with outcomes after HCT. (2) We tested SNP alleles in HLA-matched sibling donors and recipients to determine whether mismatching in the recipient is associated with graft-versus-host disease (GVHD) or the risk of recurrent malignancy after HCT. Such associations would suggest that the peptide encoded by the SNP allele functions as a minor histocompatibility antigen. (3) We performed in silico candidate SNP studies to determine the validity of previously published results showing associations with outcomes after HCT. The study population represents a large cohort from the Fred Hutchinson Cancer Research Center and consists of 4,471 recipients and 4,628 donors containing 4,258 recipient-donor pairs. Recipients suffered from a hematologic malignancy or myelodysplastic syndrome and were treated in a highly structured clinical research environment with comprehensive monitoring and systematic data recording. We used proportional hazards analyses to test for associations with acute and chronic GVHD, acute kidney injury, gram-negative bacteremia, invasive fungal disease, CMV infection and disease, recurrent malignancy, death not attributable to recurrent malignancy, and death after recurrent or progressive malignancy.

  Study phs001918

• International Verapamil SR/Trandolapril [INVEST] Genes Study

  INternational VErapamil SR-Trandolapril STudy (INVEST) was a prospective, multicenter, randomized, open-label, parallel-clinical trial that evaluated blood pressure response and adverse outcomes in patients randomized to either an atenolol-based or a verapamil SR-based hypertension treatment strategy in 22,576 patients with documented coronary artery disease and hypertension (PMID: 9809930,14657064). Hydrochlorothiazide and trandolapril were added as needed to achieve BP control or end organ protection in a protocol-defined manner. Briefly, the protocol required patients to be followed up at bassline, 6, 12, 18 and 24 weeks and then every 6 months thereafter until 2 years after the last patient was enrolled. At each visit, patients had BP and heart rate measured, clinical assessment performed, and additional antihypertensive medications added as needed to meet JNC VI blood pressure goals. The primary outcome was the first occurrence of all-cause death, nonfatal myocardial infarction (MI), or nonfatal stroke (clinicaltrials.gov identifier: NCT00133692). The genetic substudy of INVEST, INVEST-GENES, collected genomic DNA samples from 5,979 INVEST study participants. INVEST-GENES samples were genotyped on the Illumina OmniExpressExome GWAS chip. This data release includes 1529 samples that passed quality control including 657 whites, 537 Hispanics and 155 blacks. Two case-control subsets were created: one for the primary outcome of all-cause death, nonfatal MI or nonfatal stroke; the other one is for new-onset diabetes. Resistant hypertension was also evaluated in 1349 participants based on the medication use and blood pressure measurements at the visit prior to experiencing study outcomes or censoring (PMID:30237584).

  Study phs002319

• DNA Methylomic Profiling of Preeclampsia Across Pregnancy

  Preeclampsia (PE) is a hypertensive, multi-system disorder of pregnancy that significantly impacts maternal and infant morbidity/mortality across the globe, as it increases risk of cardiovascular disease and remains a leading killer of women and babies. Despite PE's significant impact on morbidity/mortality, there are no clinically reliable biomarkers that predict PE. DNA methylation, a dynamic regulator of gene expression, represents a mechanism that is known to be impacted by the environment. Because PE stems from a dysfunctional placenta that releases debris into the maternal circulation, we hypothesized that the in-vivo environment created by the dysfunctional placenta will impact DNA methylation in the maternal circulation, and that these blood-based methylation profiles would serve as a systemic biomarker of the maternal response to placental dysfunction. Our overall objective of this pilot study was to longitudinally characterize DNA methylation profiles across the three trimesters of pregnancy in the maternal blood at time points before and after clinically overt PE using a targeted (endoglin and endoglin-related genes) and a discovery-based approach. For this pilot study, 28 normotensive control participants and 28 PE case participants enrolled in the NICHD funded pregnancy study entitled Prenatal Exposures and Preeclampsia Prevention: Mechanisms of Preeclampsia and the Impact of Obesity (PEPP3; P01HD30367) were 1:1 frequency matched on self-reported race, pre-pregnancy BMI, smoking history, and gestational age at sample collection. Methylation data were collected with the Infinium® MethylationEPIC Beadchip. Methylation assay data collection were carried out at Johns Hopkins University Genetic Resources Core Facility, The SNP Center, Baltimore, MD, USA.

  Study phs001937

• Rare Diseases Clinical Research Network (RDCRN) Vasculitis Clinical Research Consortium (VCRC) Longitudinal Protocol for Polyarteritis Nodosa

  The development and validation of accurate biological markers and predictors of disease activity and outcome in Polyarteritis Nodosa (PAN), a form a idiopathic vasculitis, would have a major positive impact on the clinical care of patients with this rare disease, be an important advance in the design of clinical trials and feasibility of new drug development, and provide important insight into the pathogenesis of this condition. Current measures of disease activity, including erythrocyte sedimentation rate (ESR) and C-reactive protein (CRP), while helpful in selected settings, are mostly considered highly flawed and markers whose poor correlation with disease flares makes them inadequate to help guide therapy. Similarly, ESR and CRP are clearly unhelpful as diagnostic tests for vasculitis. The current state of clinical investigation for vasculitis relies heavily upon determination of disease status solely by clinical presentation and investigator opinion. Thus, discovery and validation of more precise markers that quantifiably measure activity, predict disease course, and correlate with an important biological process, would be of great importance. Knowledge to be gained from this study could potentially be highly important. Discovery of effective biomarkers of vasculitis and assessment of long term disease course and complications by the collection of clinical and diagnostic imaging studies proposed could lead to better care and less toxic treatment regimens. Furthermore, insight into the pathophysiology of vasculitis could be gained and this might lead to better treatments and improved outcomes in terms of reduction of vascular and treatment related complications. Ideally, excellent biomarkers reflect a sophisticated understanding of the pathophysiology of a disease.

  Study phs000590

• Melbourne Collaborative Cohort Study DNA Methylation Studies

  This dataset contains raw Illumina 450K blood DNA methylation data from a subset of participants in the Melbourne Cohort Study (MCCS), a prospective study of 41,513 healthy adult volunteers (24,469 women) aged between 27 and 76 years when recruited between 1990 and 1994. Nested case-control studies: DNA methylation data were generated as part of cancer case-control studies nested in the MCCS. Participants were cancer-free at blood draw; blood samples were taken at baseline (1990-1994) for 97% of participants; and for 3% of participants at the second wave of follow-up (2003-2007). Eight separate studies were conducted of breast, prostate, colorectal, lung, kidney, urothelial and gastric cancer and B-cell lymphoma, for a total of > 3,500 cancer cases. Controls were individually matched to cases on age, sex, and country of birth using incidence density sampling. Additional matching on smoking history was made for the study of lung cancer. Longitudinal study: For a subset of 1,100 participants with baseline DNA methylation measures (from dried blood spots) who were selected as controls in the nested case-control studies, repeated methylation measures were made using wave 2 follow-up samples (also from dried blood spots) to study longitudinal DNA methylation changes. Project aims: 1. Nested case-control studies: To assess prospective associations between peripheral blood DNA methylation and risk of eight cancer types (breast, prostate, colorectal, lung, kidney, urothelial cell and gastric cancer, and mature B-cell neoplasms). 2. Longitudinal study: To assess associations between lifestyle changes and changes in peripheral blood DNA methylation.

  Study phs003213

• Cerebrospinal fluid cfDNA sequencing for classification of central nervous system glioma

  Primary central nervous system (CNS) gliomas can be classified by characteristic genetic alterations. In addition to solid tissue obtained by surgery or biopsy, cell-free DNA (cfDNA) derived from cerebrospinal fluid (CSF) is an alternative source of material for genomic analyses. Experimental design: We performed targeted next-generation sequencing (NGS) of CSF cfDNA in a representative cohort of 85 patients presenting with with suspicion of primary or recurrent glioma at two neurooncological centers. Copy-number variation (CNV) profiles, single nucleotide variants (SNVs), and small insertions/ deletions (indels) were combined into a molecular-guided tumor classification. Comparison with the solid tumor was performed for 38 cases with matching solid tissue available. Results: Cases were stratified into four groups: glioblastoma (n = 32), other glioma (n = 19), non-malignant (n = 17) and no confirmed diagnosis available (n = 17). We introduce a molecular-guided tumor classification, enabling identification of tumor entities and/ or cancer specific alterations in 75.0 % (n = 24) of glioblastoma and 52.6 % (n = 10) of other glioma cases. The overlap between CSF and matching solid tissue was highest for CNVs (26-48 %) and SNVs at pre-defined gene loci (44 %), followed by SNVs/indels identified via uninformed variant calling (8-14 %). A molecular-guided tumor classification was made 23.5 % (n = 4) of cases with no confirmed diagnosis available. Conclusions: We developed a workflow for targeted sequencing of CSF cfDNA as well as a strategy for interpretation and reporting of sequencing results based on a molecular-guided tumor classification in glioma.

  Study EGAS50000000060

• Single Cell and Spatial Transcriptomic Profiling of Haemophilus ducreyi Infection

  We investigated the immune response in end-point pustules formed by Haemophilus ducreyi in volunteers using an experimental infection model. Six volunteers were infected in the skin of the upper arm at three sites with 41-85 CFU of H. ducreyi loaded on an allergy testing device; a sham-inoculated (e.g., wound) site was also performed. Five volunteers (4 men and 1 woman; 2 Asians and 3 Whites; aged 27-46 years) formed pustules 6-8 days post infection; 1 volunteer spontaneously resolved all sites. If a volunteer formed pustules, biopsies were performed to collect their pustule and wound sites. Biopsy pairs for all 5 pustule formers were subjected to single cell (sc) RNA-seq. Sequencing libraries were prepared using the 10X Genomics Single-cell 3' RNA-seq kit. Spatial transcriptomics was performed on biopsy pairs from 4 of the 5 pustule formers. Ten micron sections were placed on 10X Genomics Visium slides for fresh-frozen tissue, and libraries were prepared with the 10X Genomics Visium spatial 3' gene expression kit. All samples were sequenced on an Illumina NovaSeq 6000. Count tables were produced with CellRanger and SpaceRanger, respectively, and Seurat was used to analyze the data. We identified 13 major cell types by scRNA-seq; the proportion of some immune cell subsets was increased in pustules compared to wound sites. We also localized the major cell types within the tissue by using the scRNA-seq data to deconvolve the spatial transcriptomic data. The FASTQ files and count tables from CellRanger and SpaceRanger are provided.

  Study phs003754

• Open_Targets_020_Epigenomes_of_Cell_Lines

  There is currently a drive to establish cell based assay systems of greater human biological and disease relevance through the use of well characterised transformed cell lines, primary cells and complex cellular models (e.g. co-culture, 3D models). However, although the field is gaining valuable experience in running more non-standard & complex cell assays for target validation and compound pharmacology studies, there is the lack of a systematic approach to determine if this expansion in cell assay models is reflected in increased human biological and disease relevance. The increasing wealth of publically available transcriptomic, and epigenome (ENCODE and Epigenome Roadmap) data represents an ideal reference mechanism for determining the relationship between cell types used for target & compound studies to primary human cells and tissues from both healthy volunteers & patients. The CTTV020 epigenomes of cell line project aims to generate epigenetic and transcriptomic profiles of cell lines and compare these with existing and newly generated reference data sets from human tissue and cell types. The aim is to identify assay systems which will provide greater confidence in translating target biology and compound pharmacology to patients. Multiple cell types commonly used within research have been grouped according to biology. Examples include erythroid, lung epithelial, hepatocyte cell types and immortalised models of monocyte / macrophage biology. This data is part of a pre-publication release. For information on the proper use of pre-publication data shared by the Wellcome Trust Sanger Institute (including details of any publication moratoria), please see http://www.sanger.ac.uk/datasharing/

  Study EGAS00001003136

• Colorectal cancer organoids expressing BRAF (fusion) genes

  Fusion genes may be oncogenic drivers and potential targets for personalized therapies in a variety of cancer types. The BRAF gene is frequently involved in oncogenic fusions, with fusion frequencies of 0.2-3% throughout different cancers. BRAF can be fused to a wide variety of genes, however, BRAF fusions rarely occur in the exact same gene configuration, making assessment of the fusion relevance and decision for drug treatment challenging. Here, we devised a colorectal cancer organoid-based platform to functionally characterize diverse BRAF fusions, containing various partner genes (AGAP3, DLG1 and TRIM24). We compared these BRAF fusions with respect to cellular behaviour, downstream signaling activation and response to targeted therapies. We found that 5’ partner choice of BRAF affects cellular localization and intracellular signaling capacities of the fusion genes. The DLG1-BRAF fusion gene showed distinct localization to the plasma membrane and exhibited increased levels of MAPK pathway activation under unperturbed conditions. Furthermore, the different BRAF fusions showed varying sensitivities to the targeted inhibition of ERK and BRAF, with the DLG1-BRAF fusion being the most sensitive. Additionally, RNA-sequencing identified distinct subsets of genes affected by the DLG1-BRAF fusion gene. Importantly, all fusion genes conveyed resistance to the clinically relevant EGFR/HER2/HER4-inhibitor afatinib, suggesting that BRAF fusions should be screened alongside other MAPK pathway alterations to identify mCRC patients amenable to cetuximab treatment. In summary, we developed a platform to efficiently assess molecular and cellular effects of fusion genes, and revealed that differential drug responses and distinct gene expression profiles can be induced by different BRAF fusions .

  Study EGAS00001003558

• Human genomic and phenotypic synthetic data for the study of rare diseases

  The purpose of this dataset is to facilitate development of technical implementations for rare disease data integration, analysis, discovery, and federated access. This synthetic dataset includes clinical and genomic data from 6 rare disease cases. It consists of 18 whole genomes (6 index cases with their parents) which have genetic background based on public human data sequenced in the context of the Illumina Platinum initiative (Eberle, MA et al. (2017)) and made available by the HapMap project (https://www.genome.gov/10001688/international-hapmap-project). In each of the cases, real causative variants correlating with the phenotypic data provided were spiked-in. The cases included in this synthetic dataset correspond to the following type of disorders: CASE 1- Congenital myasthenic syndrome (Autosomal Dominant -de novo variant) CASE 2- Macular dystrophy (Autosomal Dominant) CASE 3- Muscular dystrophy (Autosomal Recessive-compound heterozygous variants) CASE 4- Mitochondrial disorder (Autosomal Recessive-consanguineous case - homozygous variant) CASE 5- Breast cancer (Autosomal Dominant) CASE 6- Similar as case 1 for patient matchmaking tests: Congenital myasthenic syndrome (Autosomal Dominant-de novo variant) For each case you will be able to download the following data: clinical information (phenopackets per individual and pedigree per family), raw genomic data (FASTQ and BAMs) and processed genomic data (vcfs). When using the data, the following should be acknowledged: the RD-Connect GPAP (https://platform.rd-connect.eu/), EC H2020 project EJP-RD (grant # 825575), EC H2020 project B1MG (grant # 951724) and Generalitat de Catalunya VEIS project (grant # 001-P-001647).

  Study EGAS00001005702

• Open_Targets_020_Epigenomes_of_Cell_Lines

  There is currently a drive to establish cell based assay systems of greater human biological and disease relevance through the use of well characterised transformed cell lines, primary cells and complex cellular models (e.g. co-culture, 3D models). However, although the field is gaining valuable experience in running more non-standard & complex cell assays for target validation and compound pharmacology studies, there is the lack of a systematic approach to determine if this expansion in cell assay models is reflected in increased human biological and disease relevance. The increasing wealth of publically available transcriptomic, and epigenome (ENCODE and Epigenome Roadmap) data represents an ideal reference mechanism for determining the relationship between cell types used for target & compound studies to primary human cells and tissues from both healthy volunteers & patients. The CTTV020 epigenomes of cell line project aims to generate epigenetic and transcriptomic profiles of cell lines and compare these with existing and newly generated reference data sets from human tissue and cell types. The aim is to identify assay systems which will provide greater confidence in translating target biology and compound pharmacology to patients. Multiple cell types commonly used within research have been grouped according to biology. Examples include erythroid, lung epithelial, hepatocyte cell types and immortalised models of monocyte / macrophage biology. This data is part of a pre-publication release. For information on the proper use of pre-publication data shared by the Wellcome Trust Sanger Institute (including details of any publication moratoria), please see http://www.sanger.ac.uk/datasharing/

  Study EGAS00001003137

• Open_Targets_020_Epigenomes_of_Cell_Lines

  There is currently a drive to establish cell based assay systems of greater human biological and disease relevance through the use of well characterised transformed cell lines, primary cells and complex cellular models (e.g. co-culture, 3D models). However, although the field is gaining valuable experience in running more non-standard & complex cell assays for target validation and compound pharmacology studies, there is the lack of a systematic approach to determine if this expansion in cell assay models is reflected in increased human biological and disease relevance. The increasing wealth of publically available transcriptomic, and epigenome (ENCODE and Epigenome Roadmap) data represents an ideal reference mechanism for determining the relationship between cell types used for target & compound studies to primary human cells and tissues from both healthy volunteers & patients. The CTTV020 epigenomes of cell line project aims to generate epigenetic and transcriptomic profiles of cell lines and compare these with existing and newly generated reference data sets from human tissue and cell types. The aim is to identify assay systems which will provide greater confidence in translating target biology and compound pharmacology to patients. Multiple cell types commonly used within research have been grouped according to biology. Examples include erythroid, lung epithelial, hepatocyte cell types and immortalised models of monocyte / macrophage biology. This data is part of a pre-publication release. For information on the proper use of pre-publication data shared by the Wellcome Trust Sanger Institute (including details of any publication moratoria), please see http://www.sanger.ac.uk/datasharing/

  Study EGAS00001003139

• Transcriptomic intra-tumor heterogeneity of colorectal cancer varies depending on tumor location within the colorectum

  Background; Intra-tumor heterogeneity (ITH) of colorectal cancer (CRC) complicates molecular tumor classification, such as transcriptional subtyping. Differences in cellular states, biopsy cell composition, and tumor microenvironment may all lead to ITH. Here we analyze ITH at the transcriptomic and proteomic levels to ascertain whether subtype discordance between multiregional biopsies reflects relevant biological ITH or lack of classifier robustness. Further, we study the impact of tumor location on ITH.MethodsMultiregional biopsies from stage II and III CRC tumors were analyzed by RNA sequencing (41 biopsies, 14 tumors) and multiplex immune protein analysis (89 biopsies, 29 tumors). CRC subtyping were performed using consensus molecular subtypes (CMS), CRC intrinsic subtypes (CRIS), and TUMOR types. ITH-scores and network maps were defined to determine the origin of heterogeneity. A validation cohort was used with one biopsy per tumor (162 tumors).ResultsOverall, inter-tumor transcriptional variation exceeded ITH, and subtyping calls were frequently concordant between multiregional biopsies. Still, some tumors had high ITH and were classified discordantly. Proximal tumors showed ITH related to differences in the microenvironment, while ITH within distal tumors were cancer-cell related. This subtype discordancy reflected actual molecular ITH within the tumors. The relevance of the subtypes was reflected at protein level where several inflammation markers were significantly increased in immune related transcriptional subtypes, which was verified in an independent cohort (Wilcoxon rank sum test; p<0.05).ConclusionOur transcriptomic and proteomic analyses show that the tumor location along the colorectum influence the ITH of CRC, which again influence the concordance of subtyping.

  Study EGAS00001004668

• A Machine Learning Tool Integrating Circulating Cell-Free DNA Methylation with Clinical Variables for Non-Invasive Diagnosis of Liver Graft Pathology

  Liver Transplant Recipients (LTRs) with elevated liver enzymes can develop graft injury due to various etiologies, such as T-cell mediated rejection (TCMR) and NASH (NASH-LT). While liver biopsy is the gold standard method for diagnosis of graft pathology, it is invasive and is associated with risks. The goal of our study was to develop a Machine Learning (ML) tool integrating clinical variables with methylation patterns on circulating DNA in plasma as a non-invasive diagnostic tool of graft injury. We generated methylation profiles of circulating DNA in a pilot study of 43 LTRs (11 NASH-LT, 19 TCMR, and 13 Control-LT), and developed an L2 multinomial logistic regression ML approach across 101 bootstrapped models to distinguish between the graft conditions. NASH was associated with distinctive methylation patterns on genes involved in fatty acid metabolism, while methylation of platelet-derived growth factors was identified in patients with TCMR. Our ML model achieved a mean multi-classification accuracy of 0.91, with mean specificity and sensitivity of 0.94 and 0.91, respectively. The model was found to be particularly adept at detecting TCMR and Control-LT, with true positive rates (TPRs) of 95% and 90%, and areas under the curve (AUROC) of 0.992 and 0.985, respectively. For NASH-LT, the models achieved a performance with a TPR of 82% and an AUROC of 0.991. These preliminary results suggest that our newly developed ML tool, leveraging cell-free DNA methylation and clinical variables, is a promising non-invasive classifier of graft pathology.

  Study EGAS00001007171

• OMKar

  The whole genome karyotype refers to the sequence of large chromosomal segments that make up an individuals genotype. karyotype analysis, which includes descriptions of aneuploidies and other rearrangements is crucial for understanding genetic risk factors, for diagnosis, treatment decisions, and genetic counseling linked to constitutional disorders. The current karyotyping standard is based on microscopic examination of chromosomes, a complex process that requires high expertise and offers Mb scale resolution. Optical Genome Mapping (OGM) technology can identify large DNA lesions in a cost-effective manner. In this paper, we developed OMKar, a method that uses OGM data to create a virtual karyotype. OMKar processes Structural (SV) and Copy Number (CN) Variants as inputs and encodes them into a compact breakpoint graph. It recomputes copy numbers using Integer Linear Programming to maintain CN balance and then identifies constrained Eulerian paths representing entire donor chromosomes. In tests using 38 whole genome simulations of constitutional disorders, OMKar reconstructed the karyotype with 88% precision and 95% recall on SV concordance and 95% Jaccard score on CN concordance. We applied OMKar to 50 prenatal, 41 postnatal, and 63 parental samples from ten different sites. OMKar reconstructed the correct karyotype in 144 out of 154 samples, covering 25 of 25 aneuploidies, 32 of 32 balanced translocations, and 72 of 82 unbalanced variations. Detected constitutional disorders included Cri-du-chat, Wolf-Hirschhorn, Prader-Willi deletions, Down, and Turner syndromes. Importantly, it identified a plausible genetic mechanism for five cases of constitutional disorder that were not detected by other technologies. Together, these results demonstrate the robustness of OMKar for OGM-based karyotyping.

  Study EGAS00001008245

• Maintenance of Brain Tumor Profile on Organotypic Brain Slice Culture (OBSC)

  We used uncultured tumor resection tissue from an NF2 mutation-driven grade II meningioma (MG-II) to investigate whether tumors engrafted onto organotypic brain slice cultures (OBSCs) maintained the genetic profile of the parent tumor. We prepared three groups of samples for whole exome sequencing (WES) from the same pool of dissociated MG-II tissue. Group HT is the original uncultured human tumor tissue (n = 3). Group CL is the parent tumor tissue expanded in standard in vitro cell culture until the minimum number of cells required for WES had grown. Because of initial cell loss and subsequent clonal expansion, this required six passages over the span of approximately one month (n = 3). Group BSHT is the uncultured tumor resection tissue engrafted onto OBSCs and subsequently dissected from the OBSCs at the conclusion of our standardized assay length (4 days; n = 4). WES analysis showed that tumor tissue engrafted onto OBSCs maintained a significant genetic resemblance to the parent tumor, while tumor tissue expanded in vitro displayed a distinctly different profile. Furthermore, the mutational profiles of all four BSHT biological replicates were markedly similar, indicating that each OBSC-engrafted tumor indeed contained a representative sample of the original patient tumor. A closer look at the hallmark NF2 mutations existing within all samples revealed that while all samples from the original tumor (HT1-3) and the OBSC-engrafted tumor (BSHT1-4) maintain the frame shift deletion at V24, this mutation was lost in all samples expanded in vitro (CL1-3) and replaced by mutations in other areas. Together, this data suggests that the rapid assay design and tumor-accommodating niche of our OBSC platform enables effective maintenance of the original patient tumor profile. The BBsplit algorithm from the BBtools suite was run on all samples to eliminate rat DNA contamination in the BSHT samples as well as to account for any biases that may result as a part of that process. Only the reads that were binned to the human reference were used for subsequent analysis. Reads were then mapped to the GRCh38 version of the human genome with BWA v0.7.17 and realigned together with ABRA2 v.23. Quality control was implemented using the GATK/Picard v4.1.7.0 toolkit. Somatic variants were called for each sample using the MuTect2 algorithm v4.1.7.0. Variants were merged into a single cohort variant call file and then converted to MAF via vcf2maf v1.6.21 tool. Variants were annotated using VEP v87. To identify mutations with potentially high biological impact, multiple filtering steps were applied to somatic mutation calling. First, we selected only the somatic variants that passed all filters from the MuTect2 FilterMutectCalls algorithm and second, only high/moderate impact (change coding) variants as defined by the VEP annotation were further analyzed. Over 1900 single nucleotide variants (SNVs) were detected across all samples. Figures that summarized the results were generated using maftools.

  Study phs003268

• FIGHT-207: Anonymized Genomic Alterations and Clinical Responses

  Background: FIGHT-207 was a phase 2 study of the FGFR1-FGFR3 inhibitor pemigatinib in patients with previously treated, locally advanced/metastatic or unresectable solid tumor malignancies harboring activating fibroblast growth factor receptor (FGFR) gene alterations. Population information: 107 patients were divided into 3 cohorts: FGFR1–FGFR3 fusions/rearrangements; n=49 Activating FGFR1–FGFR3 non-kinase domain single nucleotide variants (SNVs); n=32 FGFR1–FGFR3 kinase domain mutations or variants of unknown significance (VUS) with potential pathogenicity; n=26 Participants on study had tumors that were grouped into the following histologies based on ≥ 5 patients: Cholangiocarcinoma, gynecologic cancers (cervical, endometrial, uterine), central nervous system (glioblastoma, low-grade pediatric glioma, astrocytoma), pancreatic cancer, breast cancer, urothelial tract/bladder cancer, non-small cell lung cancer, and other (adrenal cancer, anal cancer, cancer of unknown primary origin, colorectal cancer, gastric/gastroesophageal cancer, gallbladder cancer, giant cell bone tumor, head and neck cancer, lung neuroendocrine cancer, nasopharyngeal cancer, ovarian cancer, prostate cancer, renal cell cancer, sarcoma, solitary fibrous tumor). Among the efficacy-evaluable participants, 99 had both independent review committee (IRC) central best overall response (BOR) and tissue NGS- data; 2 additional patients had Not Evaluable (NE) as central BOR Baseline tissue targeted NGS data (F1CDx, Foundation Medicine Inc.) of genomic alterations are reported for N=101 participants Baseline plasma targeted NGS analysis (PredicineCare, Predicine Inc.) of genomic data are reported for N=83 participants; data at disease-progression are reported for N=78 participants. Principal Findings: The FIGHT-207 study provided evidence of clinical benefit of pemigatinib in multiple histologies, explored the clinical actionability of various FGFR1-FGFR3 gene alterations, and leveraged the depth of translational data from targeted NGS analysis of baseline samples and plasma samples obtained at baseline and end of treatment to provide key insights into the biology of FGFR inhibition and the clinical utility of FGFR inhibitors. The FIGHT-207 article (pending in Nat.Med. NMED-A128973B) reports evidence suggesting clinical acquired resistance to FGFR inhibition via secondary FGFR mutations as well as emerging co-mutations in other oncogenic and tumor suppressor pathways. This study also provides evidence of acquired resistance to FGFR inhibition in multiple histologies beyond cholangiocarcinoma and urothelial cancers in a systemic correlative analysis of post-progression ctDNA in a trial. Data available through dbGaP: Anonymized information for 101 participants with both IRC central BOR evaluation (including 2 patients with NE as BOR) and tissue NGS data, including tumor histology, enrollable FGFR alteration, and outcome. Genomic alterations determined by baseline tissue NGS (F1CDx, Foundation Medicine Inc.) Genomic alterations determined by plasma NGS analysis (PredicineCare, Predicine Inc.) of ctDNA analysis at baseline (n=83) and at end of treatment/ disease progression (n=78) including genomic alterations that were not assessed to be Germline SNPs.

  Study phs003590

• Epitope-linked Ig-seq of self-reactive plasma cells in celiac disease

  Study EGAS00001003658

• DAC for Transcriptome analysis in very preterm infants with chronic lung disease after birth

  Dac EGAC00001000698

• Evolutionary predictability of genetic versus non genetic resistance to anticancer drugs in melanoma

  Dac EGAC00001002126

• Somatic mutations predict an aggressive phenotype in meningioma but do not drive grade progression

  Dac EGAC00001002858

• RHD_SA_HC24_Controls

  Healthy volunteers recruited in Samoa

  Dataset EGAD00010000963