1248 results for ""halted+early"+"slower-than-anticipated+enrollment"+hospitalized+oral+adaptive+platform"

in 28.97 milliseconds.

• Cancer gene panel (T200.1) sequencing analysis of adult type ovarian granulosa cell tumors (Validation cohort from Hillman, et al)

  Cancer gene panel (T200.1) sequencing data from tumor/normal pairs for adult type ovarian granulosa cell tumor sequencing project. This data set contains 55 tumor panel sequencing data and 44 matched normal panel sequencing data generated using the MD Anderson Cancer Center T200.1 cancer gene hybrid capture platform, with sequencing performed on an Illumina HiSeq 2000. This dataset contains BAM files generated by aligning paired-end reads to the hg19 reference genome.

  Dataset EGAD00001004091

• Dataset of PGD PGS study in CITIC Xiangya and BGI

  A total of 395 couples were subjected to IVF-PGD treatment, including 129 couples with NGS-based test and 266 couples with SNP array based test for the detection of embryonic chromosomal abnormalities. The NGS test was performed using low coverage whole genome sequencing with HiSeq 2000 platform. And the SNP array test was using Affymetrix Gene Chip Mapping Nsp I 262K. The average age of patients was 32.1 years (age range 20-44 years).

  Dataset EGAD00001001037

• Colorectal cancer samples WES

  The whole exome was sequenced in two cancer-affected members (II:1 and III:1) of the family. The family subject of this study showed an autosomal dominant mode of CRC inheritance, fulfilling the Amsterdam I clinical criteria with three CRCs in two consecutive generations. The exome capture was performed using SureSelectXT Human All Exon V3 (51Mb, Agilent Technologies), and the library was sequenced on an Illumina HiSeq 2000 platform with paired-end reads of 101bp and a 50x average coverage depth.

  Dataset EGAD00001009170

• Methylation profiling of human lung fibroblasts in COPD

  Primary lung fibroblast were isolated from well-matched control donors (no COPD, n=3) and patients with COPD (GOLD stage I-IV, n=8). Genomic DNA of cultured human lung fibroblast was isolated at passage 3, fragmented by tagmentation, and subjected to bisulfite treatment. 100 bp paired-end reads were generated from DNA libraries on Illumina HiSeq2500 platform.

  Dataset EGAD00001009406

• shallow WGS of cell free DNA

  12.5 ng of cfDNA was used as input for shallow whole-genome sequencing (sWGS), aiming for a coverage of x0.2-0.4-fold. Library preparation was performed using the TruSeq Nano DNA High Throughput Library Prep Kit (Illumina, San Diego, CA, USA) on an automated Hamilton STAR liquid handling system (Hamilton, Germany GmbH, Robotics, Gräfeling, Germany) with dual indexing, and sequencing was performed on the NextSeq500/550 platform (Illumina). The fraction of tumor-derived DNA in cell-free DNA was estimated using the R package ichorCNA.

  Dataset EGAD00001009796

• Fastq files used for searching for variants associated with endometriosis at 9p21 region

  We performed target re-sequencing for 1.29 Mb interval of chromosome 9 (chr9:21299764–22590271, hg19). NimbleGen SeqCap EZ choice system was used as a target enrichment method (Roche Diagnostics). A DNA probe set complementary to the target region was designed by NimbleDesign. The libraries were sequenced on the Illumina MiSeq platform with 2×150-bp paired-end module (Illumina). Fastq files for 48 Japanese patients with endometriosis are deposited.

  Dataset EGAD00001001942

• Merged analysis-ready bam files: HiSeq sequencing of matched tumour/normal DNA samples from Pancreatic Ductal Adenocarcinoma cases

  Additional sequencing data for 173 donors in EGAS00001000154, a study of Pancreatic Ductal Adenocarcinoma. WGS libraries were used for high-cellularity cases, WXS sequencing to high depth on low-cellularity cases. HiSeq 2xxx platform was used in all cases. The analysis files associated with this dataset are merged, de-duplicated bams aligned against GRCh37, one tumour and one normal bam per donor.

  Dataset EGAD00001002192

• 762 whole exome sequencing samples from the Singapore Living Biobank

  The dataset includes a subset of 762 individuals that were found to be closely related (≤3rd degree), including 263 Chinese and 499 Malays from the Singapore Living Biobank. There samples are whole-exome sequenced on Illumina HiSeq2000 platform (125bp paired end) with the exonic regions being captured using the Nimblegen SeqCap EZ Exome v3 kits.All the files are in the BAM format.

  Dataset EGAD00001003819

• 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

• Single-cell expression of Hodgkin lymphoma

  Single-cell gene expression was profiled for 22 Hodgkin lymphoma tumors and 5 reactive lymph nodes (2 replicates were performed for RLN-1). Library preparation was performed with the 10x Chromium platform (3' version 2 assay). Sequencing was performed on an Illumina NextSeq. The BAM files were generated from the raw sequencing data using Cell Ranger (v2.1.0) mkfastq and count commands.

  Dataset EGAD00001005739

• Single-cell RNA sequencing of erythroid and megakaryocytic acute myeloid leukemia patient cells

  Single-cell RNA sequencing was performed on bone marrow mononuclear cells of a patient with acute myeloid leukemia with erythroid differentiation of the blasts and on peripheral blood mononuclear cells of a patient with acute myeloid leukemia with megakaryocytic differentiation of the blasts. The dataset contains raw fastq files of these two samples with single-cell RNA sequencing performed using the 10x Genomics platform.

  Dataset EGAD00001009865

• RNA-Seq of GM adipose tissue samples

  This dataset contains 210 fastq files (RNA sequencing was performed in two centers) from 105 individuals (106 files in subcutaneous tissue and 104 files in visceral tissue). Of the 210 fastq files, 129 files are in PEx100 mode (appeared in a single fastq file) and 81 files are in PEx49bp mode (appeared in two separate fastq files). Sequencing was done on the Illumina HiSeq2000 platform.

  Dataset EGAD00001010253

• Analysis of Donor Pancreata Defines the Transcriptomic Signature and Microenvironment of Early Neoplastic Pancreatic Lesions

  The adult healthy human pancreas has been poorly studied given lack of indication to obtain tissue from the pancreas in the absence of disease and rapid postmortem degradation. We obtained pancreata from brain dead donors thus avoiding any warm ischemia time. We found that neoplastic lesions occur frequently in healthy organs, in donors as young as in their 3rd decade of life. Using the 10X Genomics Platform, we performed single cell RNA sequencing on 7 donor pancreata, 6 of which we separately sequenced tissue from the pancreas head and tail, for a total of 11 sequencing runs. Of note, because one of our runs (containing sequencing from pancreas head and tail) did not pass qc, our final analysis in our study utilized 6 donor pancreata, 5 of which contained pancreas head and tail sequenced separately. This is a robust single-cell dataset of healthy, nonpathologic pancreas tissue and includes acinar, ductal, and non-epithelial cells (myeloid cells, fibroblasts, endothelial cells, lymphocytes).Briefly, the donor pancreas was dissected by a clinically-trained pancreatobiliary surgeon. The organ was dissected into head, body, and tail, with portions of each placed into DMEM media with 1% BSA/10µM Y27632. Tissue was minced into 1mm3 pieces, then digested with 1 mg/mL collagenase P for 20-30 min at 37°C with gentle agitation. Digested tissue was rinsed three times with DMEM/1% BSA/10µM Y27632, then filtered through a 40µm mesh. Resulting cells were submitted to the University of Michigan Advanced Genomics Core for single cell sequencing using the 10x Genomics Platform. FASTQ files of all sequencing runs along with clinical annotation of donors is available through this dbGaP submission.

  Study phs003229

• Clonal Lineage Tracing of Primary Human Cortical Progenitors, Cell Type Profiles in the Brain Vasculature and Genotyping Data for 22q11DS and Control iPS Lines

  We sought to characterize the cell types produced by individual human cortical progenitors and describe their lineage relationships. We labeled individual human cortical cells with a massively complex lentivirus library encoding a GFP reporter gene and a molecular barcode that could be captured by standard 3' scRNA-seq methodologies. We then cultured the labeled human cells for 6 weeks in either a 1) mouse cortical astrocyte co-culture system or 2) in the mouse cortex as a xenograft. In a separate experiment, we maintained human cortical tissue slices in organotypic slice culture for 12 days. GFP+ cells were then isolated by FACS and then captured on the 10x chromium scRNA-seq platform. An additional sample was labeled by lentivirus and briefly cultured for 3 days prior to being mixed with mouse 3T3 cells in order to perform a cell mixing experiment ("barnyard") to benchmark our methodologies. We found that human individual cortical progenitors gave rise to both excitatory and inhibitory neurons as well as glia.We also sought to characterize the adult brain vasculature in both vascular malformations and non-malformed tissue. We use the 10x chromium scRNA-seq platform across 10 individuals (5 control and 5 arteriovenous malformations). We find broad disregulation across multiple cell types including the immune cells and find a specific monocyte subtype to contribute to a rupture phenotype. We also find a novel population of fibromyocytes in both conditions.Finally, we confirmed the genotype status of iPS lines that were derived from either karyotypically normal control individuals or from DiGeorge Syndrome patients carrying the 22q11.2 deletion using the Illumina Infinium Global Screening Array v3.0.

  Study phs002624

• Rapid Acceleration of Diagnostics - Digital Health Technologies (RADx-DHT): COVID-19 Experience Study (C19EX) Survey

  This was conducted virtually through the Achievement studies platform during the current COVID-19 pandemic. Participants were asked to complete a survey every day to capture information about whether they had experienced symptoms corresponding to respiratory, ILI, and COVID-19 infections within the previous 24 hour period, their experiences with the healthcare system, treatments, diagnostic testing, and their behaviors and potential risk factors. Participants were also asked to share their wearable activity tracker data. The purpose of this study was to better understand the geographic spread of diseases, impacts on daily life, and behavioral and physiological functioning in relation to recent self-reported respiratory disease, influenza-like-illness (ILI), and coronavirus disease (COVID-19) events.DOI: https://rapids.ll.mit.edu/10.57895/6m5z-je42

  Study phs002537

• Chromatin Accessibility Landscape of Human Pancreatic Ductal Adenocarcinoma (PDAC)

  Therapeutic options in pancreatic ductal adenocarcinoma (PDAC) are largely limited to cytotoxic chemotherapy without the benefit of molecular markers predicting response. By ATAC-seq analyses of EpCAM+ PDAC malignant epithelial cells sorted from 54 freshly resected human tumors, we discovered a signature of 1092 chromatin loci displaying differential accessibility between patients with disease-free survival (DFS) < 1 year and patients with DFS > 1 year. Using this signature, we further develop a chromatin accessibility microarray methodology termed “ATAC-Array”, an easy-to-use platform obviating the time and cost of next-generation sequencing. PDAC prognosis can be predicted by ATAC-array, which represents a low-cost, clinically feasible technology for assessing chromatin accessibility profiles.

  Study phs002394

• Mapping Genotypes to Chromatin Accessibility Profiles in Single Cells

  In somatic tissue differentiation, chromatin accessibility changes govern priming and precursor commitment towards cellular fates1–3. Therefore, somatic mutations likely alter chromatin accessibility patterns, as they disrupt differentiation topologies leading to abnormal clonal outgrowth. However, defining the impact of somatic mutations on the epigenome in human samples is challenging due to admixed mutated and wild-type cells. To chart how somatic mutations disrupt epigenetic landscapes in human clonal outgrowths, we developed Genotyping of Targeted loci with single-cell Chromatin Accessibility (GoT-ChA). This high-throughput platform links genotypes to chromatin accessibility at single-cell resolution, across thousands of cells within a single assay. We applied GoT-ChA to CD34+ cells from myeloproliferative neoplasm (MPN) patients with JAK2V617F-mutated hematopoiesis.

  Study EGAS50000000164

• Multidimensional and Longitudinal Immune Profiling of Sepsis in Uganda

  We conducted a prospective, observational cohort study of adults (RESERVE-U-2-TOR) admitted to Tororo General Hospital in eastern Uganda with severe, undifferentiated infection (i.e., suspected sepsis). Briefly, whole-blood samples were collected in PAXgene blood RNA tubes (PreAnalytiX, Qiagen, Germantown, MD, USA), from which RNA was extracted using PAXgene Blood RNA Kits (cat. no. 762164) (Qiagen). Sequencing libraries were constructed with the NEBNext Ultra II RNA Library Preparation Kit for Illumina, after which libraries were multiplexed and sequenced on the Illumina NovaSeq X Plus platform (Illumina, Inc, San Diego, CA). Data from this study available through dbGaP include raw RNA-Seq data generated from whole-blood samples collected upon RESERVE-U-2-TOR study enrollment (N=274).

  Study phs003914

• Development of Novel Chondrosarcoma Organoid Models for Drug Discovery

  Chondrosarcoma is a rare and aggressive malignant bone tumor characterized by resistance to conventional chemotherapy and radiotherapy. Its pathogenesis remains poorly understood, although recurrent mutations such as IDH1 have been implicated in tumor development. We treated patients with chondrosarcoma at the Osaka International Cancer Institute and established two organoid cultures from resected tumor specimens using a modified air-liquid interface method. After serial passaging, the organoids were successfully xenografted into NOD-scid IL2Rgnull (NSG) mice. The established organoids retained key histological features and genetic characteristics of the original tumors. These organoid models provide a novel and reliable platform for studying the biology of chondrosarcoma and may facilitate the development of effective therapeutic strategies for this treatment-resistant tumor.

  Study JGAS000834

• Single cell RNAseq data of human neurons, Bouwen et al Nat Comm 2025

  Brain tumor patients often suffer from epilepsy, but the underlying neuronal changes leading to this neurological symptom are not well understood. This study examined the transcriptomic profiles of human cortical neurons collected from brain tumor patients with or without seizures. The goals of the study were to identify the molecular identities of the recorded neurons and confirm that they are layer 2/3 pyramidal neurons rather than neuron-like tumor cells; and to compare the differential gene expression profiles between patients with and without epilepsy. For each patient, cortical neurons were rapidly isolated from surgically resected tissue and prepared using the Smart-seq2 protocol. Samples from 12 patients were sequenced on an Illumina HiSeq 2500 platform to generate their transcriptomic profiles.

  Study EGAS50000001369

• Hematopoietic differentiation at single-cell resolution in NPM1-mutated AML

  To investigate the relationship between somatic mutations and phenotypic hematologic differentiation at the single-cell level, we used a droplet-based multi-omics single-cell platform on eleven NPM1-mutated AML diagnostic samples. We developed a bioinformatics framework to perform phylogeny-driven genotype correction, that allowed us to study 52 103 single cells. Intra-leukemic genetic heterogeneity was detectable in all patients, including a branched architecture in nine of them, always owing to co-occurring signaling mutations. We identified two groups of NPM1-mutated AML, one characterized by a progenitor immunophenotype and a second one with a predominant monocytic differentiation. We also identified various degrees of intra-leukemic immunophenotype heterogeneity, sometimes associated with strong genetic/phenotype correlations.

  Study EGAS00001006565

• single-cell RNA-seq Case-Control study of children progressing to Type1 diabetes

  Single-cell RNA sequencing was carried out on four selected PBMC samples of Finnish children at risk of developing Type 1 diabetes and their gender age and HLA matched control children using 10X genomic platform. All four Case children were positive for multiple islet specific autoantibodies and two of them also progressed to clinical disease during the follow up whereas the control children remain negative for all autoantibodies. Age at seroconversion for Case 2, 3, 5, and 9 children is 12, 18, 24, and 18 months, respectively. Age at sampling, in months, for the pairs was as follows (Case/Control): pair 2:24/24; pair 3: 12/18; pair 5: 12/12; pair 9:24/18.

  Study EGAS00001004070

• Immune induction strategies to enhance the sensitivity to PD-1 blockade in metastatic triple negative breast cancer: the TONIC-trial

  The response rate in metastatic triple negative breast cancer (TNBC) to PD-1 blockade is low, highlighting an urgent clinical need for strategies that render the TNBC tumor microenvironment (TME) more sensitive to PD-1 blockade. Immunomodulatory mechanisms have been proposed for both chemotherapy and irradiation, but it has not been established whether these therapies may improve efficacy of PD-1 blockade by favorably changing the TME. In the first stage of this adaptive, non-comparative phase II trial (TONIC-trial; NCT02499367), 67 patients with metastatic TNBC were randomized to nivolumab without induction or to one of four induction treatments, consisting of irradiation of one metastatic lesion (3x8 Gy) or a two- week low-dose regimen of cyclophosphamide, cisplatin or doxorubicin, all followed by nivolumab. In the overall cohort of 66 evaluable patients, the objective response rate (ORR; iRECIST16) was 20% (95% CI: 11%-31%), with two complete responses and 11 partial responses. The majority of clinical responses were observed on nivolumab in the cisplatin (ORR 23%; 3/13) and doxorubicin (ORR 35%; 6/17) cohorts. After doxorubicin and cisplatin induction, we detected an upregulation of immune-related genes, involved in PD-1/PD-L1, and T-cell cytotoxicity pathways. This was further supported by enrichment among upregulated genes related to inflammation, JAK-STAT and TNFα-signaling after doxorubicin. In addition, we observed a trend towards increased T-cell infiltration, measured using T-cell receptor (TCR) sequencing, after doxorubicin. Together, the clinical and translational data of this study testing different immune induction strategies prior to nivolumab suggest that short-term doxorubicin and cisplatin may induce a more favorable TME and increase the likelihood of response to PD-1 blockade in TNBC. These data warrant further confirmation in TNBC and exploration of induction treatments prior to PD-1 blockade in other cancer types.

  Study EGAS00001003535

• Reconstructing the dispersals and adaptive history of Bantu-speaking populations in Africa and North America

  Bantu languages are spoken by ~310 million Africans, yet the genetic history of Bantu-speaking populations remains largely unexplored. We generated genomic data for 1,318 individuals from 35 populations in western central Africa, where Bantu languages originated. We found that early Bantu speakers first moved southward, through the equatorial rainforest, before spreading toward eastern and southern Africa. We also found that genetic adaptation of Bantu speakers was facilitated by admixture with autochthonous populations, particularly for the HLA and LCT loci. Finally, we identified a major contribution of western central African Bantu speakers to the ancestry of African Americans, whose genomes present no strong signals of natural selection. Together, these results highlight the contribution of Bantu-speaking peoples to the complex genetic history of Africans and African Americans.

  Study EGAS00001002078

• Combined MEK and BCL-2/XL inhibition is effective in high-grade serous ovarian cancer patient-derived xenograft models and BIM levels are predictive of responsiveness

  Most patients with late stage high-grade serous ovarian cancer (HGSOC) initially respond to chemotherapy but inevitably relapse and develop resistance, highlighting the need for novel therapies to improve patient outcomes. The MEK/ERK pathway is activated in a large subset of HGSOC, thus making it an attractive therapeutic target. Here, we systematically evaluated the extent of MEK/ERK pathway activation and efficacy of pathway inhibition in a large panel of well-annotated HGSOC patient-derived xenograft (PDX) models. The vast majority of models were nonresponsive to the MEK inhibitor cobimetinib (GDC-0973) despite effective pathway inhibition. Proteomic analyses of adaptive responses to GDC-0973 revealed that GDC-0973 upregulated the pro-apoptotic protein BIM, thus priming the cells for apoptosis regulated by BCL2-family proteins. Indeed, combination of both MEK inhibitor and dual BCL-2/XL inhibitor (ABT-263) significantly reduced cell number, increased cell death and displayed synergy in vitro in most models. In vivo, the GDC-0973 and ABT-263 combination was well tolerated and resulted in greater tumor growth inhibition than single agents. Detailed proteomic and correlation analyses identified two subsets of responsive models – those with high BIM at baseline that was increased with MEK inhibition and those with low basal Bim and high pERK levels. Models with low BIM and low pERK were non-responsive. Our findings demonstrate that combined MEK and BCL-2/XL inhibition has therapeutic activity in HGSOC models and provide a mechanistic rationale for clinical evaluation of this drug combination as well as the assessment of the extent to which BIM and/or pERK levels predict drug combination effectiveness in chemoresistant HGSOC.

  Dataset EGAD00001005111

• Longitudinal profiling of the immune response to Plasmodium vivax in naive hosts by RNA-sequencing

  Plasmodium vivax offers unique challenges for control and elimination, and may prove a tougher hurdle to overcome than Plasmodium falciparum. And yet compared to P. falciparum we know very little about the innate and adaptive immune responses that need to be harnessed to reduce disease and transmission. We recently generated a blood bank of a new clonal field isolate of P. vivax (PvW1) for human challenge studies and used systems immunology tools to track the host response throughout infection and convalescence. As part of this study, RNA-sequencing was used to resolve changes in whole blood gene expression through time in 6 volunteers (7-9 time-points per volunteer). In summary, these data show that P. vivax induces two distinct transcriptional programmes in whole blood during and after infection. During infection, transcriptional profiling reveals the rapid mobilisation of an emergency myeloid response, which leads to systemic inflammation and the recruitment of all major T cell subsets into lymphoid tissues. Six days after infection, this innate response subsides and a transcriptional signature of proliferation is revealed. This most likely represents widespread activation of lymphocytes, which return to the circulation after parasite clearance - transcriptional profiling of T cells at this time-point could therefore reveal the outcomes of critical cell-cell interactions that take place within the spleen during infection. 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/ .

  Dataset EGAD00001006924

• ETMR_Nanostring

  Total RNA (100ng) from 21 ETMRs with C19MC structural alterations and 28 other PBTs was prepared with nCounter miRNA Sample Prep Kit according to standard protocol. miRNA expression profiling was conducted with human v1, v2, or v3 miRNA panel on nCounter miRNA expression platform (NanoString Technologies, Seattle, WA) according to manufacturer’s protocol. Signal normalization was done using nSolver Analysis and batch corrected using ComBat (Johnson et al. Biostatistics. 2007). 565 miRNAs overlapped between all three versions and was used for further analyses. Fold change and supervised t-test with FDR correction was calculated between the ETMRs and other PBTs.

  Dataset EGAD00010001701

• MassArray1-80

  234 samples genotyped at 40 loci using the MassArrayiPLEX genotyping assay using the iPLEX Gold genotyping kit (Agena Biosciences, cat. 10148-2) Gabriel et al. (2009) [Gabriel, S. , Ziaugra, L. and Tabbaa, D. (2009), SNP Genotyping Using the Sequenom MassARRAY iPLEX Platform. Current Protocols in Human Genetics, 60: 2.12.1-2.12.18. doi:10.1002/0471142905.hg0212s60]). Products were detected on a MassArray mass spectrophotometer and data were acquired in real time with MassArray RT software 4.0.0.2 (Agena Biosciences). SNP clustering and validation was carried out with Typer 4.0.26.75 software (Agena Biosciences).

  Dataset EGAD00010001906

• RNA-seq from Glioblastoma treated with Indisulam

  The dataset includes RNA-sequencing results from four patient-derived glioblastoma cell lines treated with DMSO (vehicle control) or the splicing modulating-drug indisulam (at 6 and 16 hours), resulting in 12 RNA-seq samples. Paired-end sequencing produced 24 FASTQ.gz files. The RNA libraries were prepared using PolyA selection and ERCC spike-ins and sequenced on a NovaSeq platform. This dataset supports the analysis of drug-induced transcriptomic changes and the prediction of subsequent non-canonical tumor-specific antigens (ncTSAs) using the NovumRNA pipeline.

  Dataset EGAD50000000957

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

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

  Dataset EGAD50000000416

• Sequencing data of the ampulla and fimbriae of the fallopian tube in pre-menopausal women

  A total of 10 pre-menopausal patients were recruited for this study. Sequencing of both the fimbriae and ampullary region of the fallopian tubes was performed using 10x Genomics single-cell RNA-seq and ATAC-seq. For one patient, data were sequenced across 4 lanes, while the remaining patients' data were sequenced in 2 lanes each, resulting in a total of 44 sequencing datasets for each platform.

  Dataset EGAD50000000889

• RIP-SeqRaw data

  This dataset contains 15 paired FASTQ files from the PTBP1 project. Sequencing data were generated using bulk directional RNA-seq and RIP-seq experiments performed on a NovaSeq 6000 platform (2×100 bp paired-end reads). The dataset comprises two groups of samples: controls and patients. For each group, both input and immunoprecipitated samples are available. Patient samples correspond to skin biopsies from individuals affected by a neurodevelopmental disorder associated with variable skeletal dysplasia and disproportionate short-limbed short stature.

  Dataset EGAD50000001723

• Transrenal DNA Analysis

  The current sequencing dataset consists of 91 whole genome sequencing data files (Fastq files) of human cell-free DNA (cfDNA) obtained from plasma and urine samples. Specifically, we extracted 20 ucfDNA and 17 plasma DNA samples from healthy pregnant women, 11 ucfDNA samples from pregnant women with preeclampsia, 19 ucfDNA samples from healthy controls, and 24 ucfDNA samples from patients with proteinuria. These extracted cfDNA samples were then constructed into DNA libraries using the TruSeq Nano DNA Library Prep Kit (Illumina) and subsequently sequenced on the Nextseq2000 platform (Illumina).

  Dataset EGAD50000001127

• Long-read single-cell RNA-seq in COVID-19

  We report the first application of long-read single-cell RNA sequencing on nasopharyngeal swabs from COVID-19 patients and healthy controls to resolve transcript-level changes across cell types. Samples were collected from three patients with moderate COVID-19, six patients with critical COVID-19, and three healthy controls. Single-cell libraries were generated using the 10x Genomics Chromium 3' protocol, producing unfragmented cDNA. Libraries were sequenced on the Oxford Nanopore Technologies PromethION platform. Basecalling was performed with Guppy (v1.6), generating a single FASTQ file per sample.

  Dataset EGAD50000001836

• RNA-seq data for proximal and distal human LHBT UZH (CH)

  This dataset contains bulk RNA-seq data from 15 patients who underwent rotator cuff repair surgery, yielding paired proximal and distal samples of the long head of the biceps tendon (30 samples total). The submission includes 90 files, consisting of R1 and R2 FASTQ files for each sample as well asprocessed .TXT files containing gene-level counts generated after genome alignment. Raw sequencing reads were generated on an Illumina platform, aligned to the human reference genome GRCh38.p13, and quantified at the gene level.

  Dataset EGAD50000002095

• Whole-exome sequencing and RNA-seq of paired normal-tumour samples from MMR-proficient early-onset colorectal cancer patients

  This dataset contains fastq files obtained from paired samples of normal colonic mucosa and tumour tissue, collected from 19 patients diagnosed with MMR-proficient colorectal cancer at an age of 50 years or younger. It includes both whole-exome sequencing and RNA-seq data, generated on the Illumina HiSeq 3000 platform. Additionally, the dataset includes phenotypic information from the patients.

  Dataset EGAD50000001844

• Shallow Whole-Genome Sequencing of Plasma ctDNA in Relapsed/Refractory Germ Cell Tumors

  This dataset comprises shallow whole-genome sequencing data (~3× coverage) of circulating tumor DNA extracted from baseline and on-treatment plasma samples of patients with relapsed or refractory germ cell tumors treated with salvage high-dose chemotherapy. Libraries were generated from 20 ng of cfDNA using the KAPA Hyper Prep protocol with unique dual indexing and sequenced on an Illumina NovaSeq 6000 platform to enable genome-wide copy number and biomarker analyses associated with treatment response and clinical outcome.

  Dataset EGAD50000002183

• Enzymatic methylation sequencing of rectal mucus from patients suspected to have colorectal cancer

  This dataset contains comprises enzymatic methylation sequencing (EM-Seq) data generated from 208 rectal mucus samples from patients suspected to have colorectal cancer and healthy controls. Targeted CpG sites were enriched using a panel of genes implicated in colorectal cancer, and libraries were prepared with NEBNext EM-Seq prior to Illumina sequencing. Sequencing was performed on the Illumina NovaSeq6000 platform, producing paired-end FASTQ files. These data support analyses of DNA methylation patterns in CRC detection and progression

  Dataset EGAD50000001871

• Targeted Next-Generation Sequencing Data of IDH1 Exon 4 in Intrahepatic Cholangiocarcinoma Samples

  This dataset contains targeted next-generation sequencing data from 76 FFPE tumor tissues focusing on IDH1 exon 4 and codon 132. Genomic DNA was isolated using the QIAamp DNA FFPE Tissue Kit and sequenced on the Illumina MiSeq platform with 200x minimum coverage. The results are provided as encrypted somatic variant call files (VCF) generated through the Nextera XT library preparation protocol. This collection represents the specific somatic mutation profiles of the intrahepatic cholangiocarcinoma cohort for controlled access.

  Dataset EGAD50000002345

• WES of breast and larynx cancer cases

  The dataset is based on 37 FFPE samples obtained from 12 patients diagnosed with breast or larynx cancer, For each patient 3 sample types were obtained P - primary tumor, L - malignant lymph node and C - benign lymph node (control). For patient G46 two malignant lymph nodes were used. DNA isolated from all samples was subject to exome selection using Agilent SureSelect Human All Exon V7. The obtained material was sequenced using NovaSeq 6000 platform with 2x150 reads. The sequencing was conducted by Novogene company.

  Dataset EGAD00001009081

• High-throughput sequencing data of immunoglobulin gene rearrangements in acute lymphoblastic leukaemia - summary .fastq and .bcl files

  Immunoglobulin heavy chain gene high throughput sequencing of paediatric acute lymphoblastic leukaemia samples, for the purpose of MRD on the Illumina MiSeq platform. This dataset contains summary fastq files and raw bcl files from the MiSeq for this study. In the study we identify errors associated with multiplexing that could potentially impact on the accuracy of MRD analysis. We optimise a strategy combining high purity, sequence-optimised oligonucleotides, dual-indexing and an error-aware demultiplexing approach to minimise errors and maximise sensitivity.

  Dataset EGAD00001001983

• RNAseq of human breast cancer tumors from the PEARL study

  Formalin fixed, paraffin-embedded human breast cancer tumor samples had RNA extracted using the Thermo Scientific KingFisher Flex instrument and the Applied Biosystems MagMAX FFPE DNA/RNA Ultra Kit; Total RNA libraries were created using the Bravo Automated Liquid-Handling Platform and the TruSeq Stranded Total RNA Library Prep Gold Kit; libraries were sequenced on the Illumina NovaSeq 6000 machine using a 2x50 bp paired-end configuration to target a read depth of 120 million clusters per library.

  Dataset EGAD00001015613

• Human CCO+ liver mtDNA sequencing

  BAM files containing paired-end mtDNA sequencing data from morphologically normal human liver. CCO-proficient hepatocytes acquired from human livers in which clonal CCO-deficient hepatocyte patches had been previously identified. Individual BAM files are named according to their patch, line and sample location, where PT denotes tissue near to the portal triad (PT), central hepatic vein (CV) and midway between these two structures (Mid). "Stroma" control samples were used for identifying germ-line variants. Sequenced on NextSeq 500 platform.

  Dataset EGAD00001010016

• V(D)J and 5' Gene Expression data of bone marrow cells from patients with aplastic anemia

  Viably frozen blood MNCs from 9 cGVHD patients were sorted with BD Influx Cell sorter, to enrich for CD45+ cells. Gene and V(D)J transcript profiles were studied with 10x Genomics Chromium Single Cell Immune Profiling platform. The Chromium Single Cell 5’RNAseq run and library preparation were done using the Chromium Next GEM Single Cell Immune Profiling version 1.1 chemistry. The raw data was processed using Cell Ranger v3.1 pipelines.

  Dataset EGAD00001012117

• National Eye Institute (NEI) Age-Related Eye Disease Study 2 (AREDS2)

  The Age-Related Eye Disease Study 2 (AREDS2) was a multi-center, randomized Phase III clinical trial designed to assess the effects of oral supplementation of high doses of lutein, zeaxanthin, and omega-3 fatty acids (docosahexaenoic acid [DHA] and eicosapentaenoic acid [EPA]) in reducing the risk of progression to late age-related macular degeneration (AMD), progression to cataract surgery, and/or progression to moderate vision loss in high-risk participants. The effect of the study supplements on cardiovascular outcomes and cognitive function were also examined. Other study goals included evaluation of eliminating beta-carotene and/or reducing zinc in the original AREDS formulation on the progression and development of late AMD. AREDS2 sought to validate the AREDS AMD scale developed from the photographic data obtained from AREDS, (Study Accession: phs000001).Eighty-two clinical sites across the United States enrolled 4,203 participants aged 50 to 85 (mean age 74 years) between October 2006 and September 2008. Enrollment was restricted to people at high risk of progression to late AMD with either bilateral large drusen or large drusen in 1 eye and late AMD in the fellow eye. Follow-up assessments in the clinic occurred on an annual basis for an average of 5 years, with telephone calls every six months during each year. Blood or saliva samples were also collected from 2,000+ AREDS2 participants for genetic research. Of these, samples from 1,800+ AREDS2 participants were included in the International Age-Related Macular Degeneration Genomics Consortium - Exome Chip Experiment, and have exome chip data available in the dbGaP (Study Accession: phs001039). In addition, samples from 1300+ AREDS2 participants were included in the International Age-Related Macular Degeneration Genomics Consortium - Whole Genome Sequencing Study in the dbGaP (Study Accession: TBD). Of 1363 AREDS2 participants with whole genome sequencing, 488 previously participated in AREDS.Please see "The Age-Related Eye Disease Study 2 (AREDS2) Research Group" document for a full list of AREDS2 study contributors.

  Study phs002015

• Whole exome sequencing of germline DNA was performed and subsequent polymorphisms in genes known and putatively involved in the innate immune response to fungi were identified

  Disease can be conceptualized as the result of interactions between infecting microbe and holobiont, the combination of a host and its microbial communities. It is likely that genomic variation in the host, infecting microbe, and commensal microbiota are key determinants of infectious disease clinical outcomes. However, until recently, simultaneous, multiomic investigation of infecting microbe and holobiont components has rarely been explored. Herein, we characterized the infecting microbe, host, micro- and mycobiomes leading up to infection onset in a leukemia patient that developed invasive mucormycosis. We discovered that the patient was infected with a strain of the recently described Mucor velutinosus species which we determined was hypervirulent in a Drosophila challenge model and has a predisposition for skin dissemination. After completing the infecting M. velutinosus genome and genomes from four other Mucor species, comparative pathogenomics was performed and assisted in identifying 66 M. velutinosus-specific putatively secreted proteins, including multiple novel secreted aspartyl proteinases which may contribute to the unique clinical presentation of skin dissemination. Whole exome sequencing of the patient revealed multiple non-synonymous polymorphisms in genes critical to control of fungal proliferation, such as TLR6 and PTX3. Moreover, the patient had a non-synonymous polymorphism in the NOD2 gene and a missense mutation in FUT2, which have been linked to microbial dysbiosis and microbiome diversity maintenance during physiologic stress, respectively. In concert with host genetic polymorphism data, the micro- and mycobiome analyses revealed that the infection developed amid a dysbiotic microbiome with low α-diversity, dominated by staphylococci. Additionally, longitudinal mycobiome data showed that M. velutinosus DNA was detectable in oral samples preceding disease onset. Our genome-level study of the host-infecting microbe-commensal triad extends the concept of personalized genomic medicine to the holobiont-infecting microbe interface thereby offering novel opportunities for using synergistic genetic methods to increase understanding of infectious diseases pathogenesis and clinical outcomes.

  Study EGAS00001001542

• Genome wide association study for early onset coronary disease and related phenotypes (ADVANCE)

  ADVANCE (Atherosclerotic Disease, VAscular functioN, and genetiC Epidemiology) is a large epidemiological study of genetic and non-genetic determinants of coronary artery disease (CAD) that started in 2000 as a collaborative effort between researchers at Stanford University and Kaiser Permanente of Northern California. The overarching goal of the study is to improve our ability to prevent, diagnose and treat CAD. The initial study included recruitment of over 3600 subjects (including 1873 subjects with incident clinically significant coronary disease and 1745 control subjects) from multiple race/ethnic backgrounds. A subset of ~ 500 subjects with very early onset coronary disease (men < 45 and women < 55) and ~ 500 similar aged controls were genotyped using the Illumina 550K platform as part of an NIH funded effort within the STAMPEED consortium.

  Study phs000423

• Identification of germline variants in Medullary thyroid carcinoma (MTC) by whole- exome sequencing

  Medullary thyroid cancer (MTC) is a rare malignant tumor that arises from parafollicular cells. Approximately 8% of thyroid cancer cases are MTC, and about 25% of these have a hereditary component. Incorporating molecular parameters into tumor classification is important. Besides, the presence of pathogenic germline variants can impact directly on cancer prevention. Thus, the aim of this study was to perform whole exome sequencing (WES) on a consecutive series of hereditary RET wild-type MTC patients to identify genetic variants that may be involved in the carcinogenesis of this tumor. WES was performed on 28 patients negative for germline RET pathogenic variants using the NovaSeq 6000 platform. Variant classification followed American College of Medical Genetics and Genomics guidelines.Our study represents a significant advancement in gene discovery for MTC genetics.

  Study EGAS50000000061

• Single-Cell Atlas of Human Liver and Blood Immune Cells Across Fatty Liver Disease Stages

  The goal of the study was to investigate immunological correlates of human fatty liver disease progression. We generated a single-cell RNA-seq (scRNA-seq) atlas of immune cells from liver fine needle aspirates (FNAs) and paired peripheral blood mononuclear cells (PBMCs) from a full-spectrum Metabolic Dysfunction-Associated Steatotic Liver Disease (MASLD)/Metabolic Dysfunction-Associated Steatohepatitis (MASH) human cohort, using the 3' 10X Genomics platform. Using computational analyses to assess changes in cellular frequencies and function, we found heightened immunoregulatory programs with profibrotic potential alongside a shift from antigen-specific to natural killer cytotoxic functions in the liver with MASH progression. Available data include raw single-cell transcriptomic data (FASTQ files) for each sample type (PBMC, FNA) per patient alongside clinical and histological measurements of fatty liver disease.

  Study phs004044

• RNA sequencing data from glioblastoma primary cell lines treated with indisulam

  This study aimed to develop NovumRNA, a bioinformatics pipeline designed to predict non-canonical tumor-specific antigens (ncTSAs) from human tumor RNA-sequencing data, potentially broadening the target pool for cancer neo-epitope-based immunotherapies. The splicing-modulating drug indisulam was investigated for its potential to induce aberrant transcriptomes, potentially increasing ncTSAs, subsequently predicted by NovumRNA. Four glioblastoma primary cell lines were derived from patient Cavitron Ultrasonic Aspirator (CUSA) material, cultured as neurospheres, and treated with indisulam or vehicle control. RNA was extracted at 6 and 16 hours post-treatment and sequenced using the NovaSeq platform. The resulting RNA-seq data was analyzed with NovumRNA, using healthy brain GTEx samples as controls, to identify and validate ncTSAs induced by indisulam treatment. NovumRNA is available at: https://github.com/ComputationalBiomedicineGroup/NovumRNA.

  Study EGAS50000000680

• Multi-omics analysis of serial samples from metastatic TNBC patients on PARP inhibitor monotherapy provide insight into rational PARP inhibitor therapy combinations

  In a pilot study, we evaluated the safety and efficacy of olaparib/durvalumab combination treatment in mTNBC patients and the feasibility of real-time deep analysis of serial tumor samples from triple negative breast cancer patients to identify mechanisms of resistance and treatment opportunities. This study used the SMMART analytic platform at OHSU KCI and incorporated comprehensive multi-omic analysis of serial liquid and tumor biopsies. Deep analysis of longitudinal biopsies combined with a robust computational biology pipeline identified multiple PARPi-induced changes in immune activation, DNA damage checkpoint activation, apoptosis and signaling pathways including RTK, PI3K-AKT and RAS-MAPK. These emergent tumor and immune state changes could act as biomarker targets to be used in selecting patient specific combination therapies.

  Study EGAS00001005479

• Patient-derived organoids as a novel tool to study cervical cancer

  Cervical cancer is the most prevalent gynecological malignancy worldwide, often caused by infection with a high-risk human papillomavirus. Currently, there are only limited number of human-derived culture systems available that enable to study the viral infection for short-term. Here, we report on establishment of long-term human-derived organoid cultures from both healthy ecto- and endocervical epithelia that closely recapitulate the tissues of origin by maintaining the authentic histological and tissue-specific gene expression profiles. Additionally, using material from patients’ Pap-brush material, a successful panel of long-term patient-derived cancer organoids was established that maintain the causative viral infection in vitro and show differential response to common chemotherapy regimens. This study provides a promising platform for cervical cancer research and studying direct virus-host interactions.

  Study EGAS00001004439

• Alterations in the gut microbiome implicate key taxa and metabolic pathways across inflammatory arthritis phenotypes

  Musculoskeletal diseases affect up to 20% of adults worldwide. The gut microbiome has been implicated in inflammatory conditions, but large-scale metagenomic evaluations have not yet traced the routes by which immunity in the gut affects inflammatory arthritis. To characterize the community structure and associated functional processes driving gut microbial involvement in arthritis, the Inflammatory Arthritis Microbiome Consortium investigated 440 stool shotgun metagenomes comprising 221 adults diagnosed with rheumatoid arthritis, ankylosing spondylitis, or psoriatic arthritis and 219 healthy controls and individuals with joint pain without an underlying inflammatory cause. Diagnosis explained about 2% of gut taxonomic variability, which is comparable in magnitude to inflammatory bowel disease. We identified several candidate microbes with differential carriage patterns in patients with elevated blood markers for inflammation. Our results confirm and extend previous findings of increased carriage of typically oral and inflammatory taxa and decreased abundance and prevalence of typical gut clades, indicating that distal inflammatory conditions, as well as local conditions, correspond to alterations to the gut microbial composition. We identified several differentially encoded pathways in the gut microbiome of patients with inflammatory arthritis, including changes in vitamin B salvage and biosynthesis and enrichment of iron sequestration. Although several of these changes characteristic of inflammation could have causal roles, we hypothesize that they are mainly positive feedback responses to changes in host physiology and immune homeostasis. By connecting taxonomic alternations to functional alterations, this work expands our understanding of the shifts in the gut ecosystem that occur in response to systemic inflammation during arthritis.

  Dataset EGAD50000000567

• Immunophenotyping in a COVID-19 Cohort (IMPACC) Transcriptomics and Genotyping Assays

  IMPACC (IMmunoPhenotyping Assessment in a COVID-19 Cohort) is a prospective longitudinal cohort study (NCT04378777) launched in May 2020 in response to the worldwide pandemic caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). It was funded by the National Institute of Allergy and Infectious Diseases (NIAID) of the National Institute of Health (NIH). Patient enrollment and sample analysis involved 20 hospitals associated with 15 U.S. biomedical research centers and 11 centralized Core immunoassay laboratories.The study aimed to enable the identification of potential biomarkers and inform future therapeutic interventions using a longitudinal approach encompassing the whole disease course for a comprehensive understanding of the contributions of the pathogen and host immune response in modulating the manifestations, severity, and post-acute sequelae of the infection. IMPACC enrolled close to 1200 adult symptomatic, molecularly confirmed hospitalized COVID-19 patients in the study within 48 hours of their hospital admission. Clinical data and biological samples (blood, mid-turbinate nasal swabs, and esophageal aspirant) were collected according to minimal risk guidelines at enrollment and on days 4, 7, 14, 21, and 28. Biological samples were collected at 3-month intervals up to 12 months after hospital discharge to assess functional and immunologic recovery measures. Sample collection, processing, and storage procedures were standardized across sites, and samples were transported to centralized assay-specific core laboratories (Core Labs) in batches for testing and analysis. The description of outcome severity was not limited to survival versus death but encompassed a clinical trajectory approach using 5 groups leveraging longitudinal data based on time in the hospital, disease severity by ordinal scale based on the degree of respiratory illness, and presence or absence of limitations at discharge. Disease severity was assessed based on the degree of respiratory illness using a 7-point ordinal scale adapted from the World Health Organization COVID-19 and NIAID disease ordinal severity scales. DNA for genetic analyses was collected from whole blood at a single time point. To identify any genomic determinants of severe COVID-19 disease, single-nucleotide polymorphism (SNP) genotyping and exome sequencing were conducted to assess genetic variants associated with individual susceptibility to severe disease. In addition, IMPACC included bulk transcriptomic analysis of upper airway (nasal swaps) samples, lower airway (esophageal aspirant) samples, and peripheral blood mononuclear cells (PBMCs) to evaluate dynamic changes in cellular composition and cellular response during the course of the disease. Reads were aligned to the GRCh38 human reference genome. Additional information for the IMPACC study has been submitted to The Immunology Database and Analysis Portal (ImmPort) under study accession SDY1760. Further information and requests for resources and reagents should be directed to and will be fulfilled by the Lead Contact, Dr. Steven Kleinstein (steven.kleinstein@yale.edu).

  Study phs002686

• Exploiting evolutionary steering in cancer therapy

  This dataset contains 9 bam files of exome sequencing for an experiment of evolved resistance. Here a barcoded cell line (HCC827 - POT) has been treated under high concentrations of gefitinib (GEF) and trametinib (TRM) until resistance has evolved, as well as under control conditions (DMSO). The dataset contains exome sequencing of confluent cells for three replicates for each anti-cancer drug as well as two replicates of growth under DMSO conditions. The original barcoded cell line (POT) was also exome sequenced and is included in the cohort. Sequencing was performed on the Illumina NovaSeq platform.

  Dataset EGAD00001005782

• Epigenomic timecourse of brain organoid development

  Single-cell Cut&Tag of three histone modifications and chromatin accessibility over a timecourse of brain organoid development from pluripotency. We profiled 5 time points of brain organoid development and 2 time points of retinal organoid development. At each time point used scCut&Tag to profile histone modifications (H3K27me3, H3K27ac, H3K4me3) as well as multiome-seq (10X) to jointly profile transcriptome and chromatin accessibility from the same cell suspension. Library preparation was carried out with the 10x genomics platform.

  Dataset EGAD50000000222

• Breakfast trial transcriptomic profiles

  The dataset consists in fastq files generated with RNA sequencing of 55 samples from 29 patients with stage I-III TNBC treated with anthracycline-taxane chemotherapy plus fasting-mimicking diet plus/minus metformin in the context of the BREAKFAST trial (NCT04248998). Samples are fresh-frozen tumor samples at baseline and 14-21 days after the first treament cycle sequenced to identify early predictors of treatment activity. Each sample is sequenced in multiple lanes (four or eight lanes each) and in paired ends mode (R1 and R2 fastq files). Samples were sequenced by an Illumina Nextseq500 platform.

  Dataset EGAD50000000968

• NGS-Based Mutational Analysis of 87 PMBL Patients from the GAINED Cohort (Subset of 382 Sequenced Patients)

  Targeted DNA sequencing was performed on DNA extracted from 87 formalin-fixed paraffin-embedded (FFPE) samples, representing a subset of the 382 sequenced patients from the GAINED cohort. A custom “Lymphopanel” was used to identify mutations in 70 genes associated with lymphomagenesis. Library preparation, exome capture, sequencing, and analysis were conducted by IntegraGen SA (Evry, France). Sequencing was performed on an Illumina HiSeq4000 platform, with variant calling and annotation using established bioinformatics tools such as MuTect and VEP.

  Dataset EGAD50000001359

• Bulk TCRseq data from 149 patients with bladder cancer

  For this dataset we performed bulk TCRseq on tumor and serial blood samples from patients with muscle invasive bladder cancer (n patients = 119, n blood = 209, n tumor = 28) or non-muscle invasive bladder cancer (n patients = 30, n blood = 56, n tumor = 19) for a total of 149 patients and 312 samples. Each sample consists of a paired fastq file. Sequenced on the Ilumina NovaSeq6000 platform using SP and S1 flow cells (v1.5, 2x101 cycles), with a mean yield of 42 million reads covering the CDR3β region.

  Dataset EGAD50000001382

• Single-cell RNA-Seq analysis of thymic ILC1 progenitors and NK cell differentiation This analysis involved a multiplexed sequencing run to study thymic innate lymphoid cells (ILCs) and NK progenitors. The generated data requires a demultiplexing file to separate and identify the individual sample tags for downstream analysis.

  This dataset contains multiplexed single-cell RNA sequencing (scRNA-seq) data from human thymic tissue, focusing on ILC1 progenitors and NK cell differentiation. The data were generated using the BD Rhapsody system and sequenced on the Illumina NovaSeq S4 platform. A demultiplexing file is required to assign sample identities.

  Dataset EGAD50000001157

• Whole-genome sequencing data of poorly differentiated thyroid carcinomas and matched blood from six patients

  This dataset contains raw sequencing reads in FASTQ format from 12 samples, comprising paired tumour and matched blood DNA from six patients diagnosed with poorly differentiated thyroid carcinoma (PDTC). Genomic DNA was extracted from fresh-frozen tumour tissue and peripheral blood using standard protocols. Whole-genome sequencing was performed on the Illumina HiSeq X Ten platform, generating paired-end reads at an average depth of approximately 20X. These data support investigations into the somatic mutational landscape and genomic alterations associated with PDTC.

  Dataset EGAD50000001628

• mRNA-seq data from ALL patients with NUP214::ABL1 disease

  Dataset contains mRNA-sequencing data (fastq files) from 2 patients with NUP214::ABL1 disease (one T-ALL and one B-ALL patient). Patient samples (peripheral blood or bone marrow) were taken at diagnosis (B-ALL) or relapse (T-ALL). mRNA was extracted from lymphoblasts and underwent paired-end sequencing (75bp) using the Illumina NextSeq platform. Transcriptomic data was used for identification of gene fusions, SNVs and InDels. mRNA-seq data for an additional B-ALL patient with NUP214::ABL1 disease utilised in this study has already been published (EGAS00001006460).

  Dataset EGAD50000001395

• The dataset for "ctDNA residual disease analyses during perioperative nivolumab or nivolumab plus ipilimumab in resectable diffuse pleural mesothelioma”

  The dataset for the study “ctDNA residual disease analyses during perioperative nivolumab or nivolumab plus ipilimumab in resectable diffuse pleural mesothelioma” includes 169 bam files from whole genome sequencing on the Illumina NovaSeq6000 platform. The samples analyzed include tumor (n=28) and normal (n=28) DNA samples, and serial plasma cfDNA (n=113) samples from 28 individuals with resectable diffuse pleural mesothelioma, treated with nivolumab or nivolumab plus ipilimumab on the NCT03918252 trial.

  Dataset EGAD50000001701

• RIP-SeqRaw data

  This dataset contains the raw count matrix generated in the PTBP1 project. Sequencing data were obtained from bulk directional RNA-seq and RIP-seq experiments performed on a NovaSeq 6000 platform (2×100 bp paired-end reads). Read counts were computed using HTSeq-count, without normalization. The dataset comprises two groups of samples: controls and patients. For each group, both input and immunoprecipitated samples are available. Patient samples correspond to skin biopsies from individuals affected by a neurodevelopmental disorder associated with variable skeletal dysplasia and disproportionate short-limbed short stature.

  Dataset EGAD50000001722

• Visium CytAssist Spatial Gene Expression analysis for glioblastoma

  The glioblastoma spatial transcriptomics dataset was generated from 4 FFPE fixed adult glioblastoma samples, using the 10x Genomics Visium platform, producing raw FASTQ files, spatial feature matrices (.h5, .mtx, .tsv), and paired histology images (.tif). Spot-level transcript counts were aligned to tissue architecture and processed in Seurat, with results stored as .rds objects. Data visualization was performed using SpatialFeaturePlot, and quantitative analyses were supported by custom Matlab scripts. The dataset provides both raw and processed files, offering reproducible spatially resolved transcriptomic profiles of glioblastoma tissue sections

  Dataset EGAD50000001767

• Transcriptome data of WS patients and controls

  Fibroblasts of 4 WS patients and 4 sex matched controls were transformed into iPSCs, which were then differentiated to Neuroepithelial Stem Cells (NESCs), and further differentiated into neurons. RNA sequencing was performed at the NESC stage and after 4 and 8 weeks of neural development for 3 replicates per individual using the Illumina TruSeq stranded library polyA method on the NovaSeq6000 platform at NGI Stockholm. The data was preprocessed using the nf-core/rnaseq (https://nf-co.re/rnaseq) that includes quality control, data cleaning, and read alignment to GRCh38 (STAR, v2.6.1d)

  Dataset EGAD50000001728

• WES for 42 patients with pleural mesothelioma (Not matched)

  The dataset contains WES data (bam files) for 42 pleural mesothelioma samples. Nextera Flex for Enrichment solution (Illumina, San Diego, CA) in combination with SureSelect Human All Exon V7 probes (Agilent, Santa Clara, CA) was used for library preparation and generated libraries were sequenced on NovaSeq 6000 (Illumina, San Diego, CA) in 150 pair-end mode. Quality control of the raw data was conducted using fastQC (v. 0.11.8) (https://www.bioinformatics. babraham.ac.uk/projects/fastqc/). WES data were then analyzed with the DRAGEN Bio IT platform 49 (version 4.2.4) and the human GRCh38 as reference genome.

  Dataset EGAD50000002127

• WES for 45 patients with pleural mesothelioma (Matched)

  The dataset contains WES data (bam files) for 45 pleural mesothelioma samples. Nextera Flex for Enrichment solution (Illumina, San Diego, CA) in combination with SureSelect Human All Exon V7 probes (Agilent, Santa Clara, CA) was used for library preparation and generated libraries were sequenced on NovaSeq 6000 (Illumina, San Diego, CA) in 150 pair-end mode. Quality control of the raw data was conducted using fastQC (v. 0.11.8) (https://www.bioinformatics. babraham.ac.uk/projects/fastqc/). WES data were then analyzed with the DRAGEN Bio IT platform 49 (version 4.2.4) and the human GRCh38 as reference genome.

  Dataset EGAD50000002128

• Transcriptomic analyisis of 54 samples of AC16 cells exposed to trastuzumab

  Data of 54 samples with their 54 paired fastaq files that were sequenced in a Novaseq 6000 platform. Samples correspond to the three biological replicates of AC16 cells (i.e. AC16, C1, C2). Each biological replicate was edited to carry either of the three different genotypes of the rs1136201 variant (i.e. AA, AG, GG) and each genotype was enriched to express HER2 protein in three levels (i.e. low, medium and high expression) as selected by FACS. Additionally, treatment of each sample was performed and sequenced in duplicates (i.e. 1 and 2)

  Dataset EGAD50000001705

• Neo-RT sWGS

  Paired plasma cell-free DNA (cfDNA) samples were collected from 11 breast cancer patients before and after radiotherapy. Sequencing libraries were prepared using the Agilent SureSelect XT HS2 kit and sequenced on the Illumina NovaSeq 6000 platform. Neo-RT (NCT03818100) is a non-randomised, single-arm feasibility study evaluating neoadjuvant radiotherapy combined with endocrine therapy in women with ER-positive, HER2-negative breast cancer. Eligible patients had grade 1 or 2 disease (grade 3 permitted if chemotherapy was contraindicated) and a palpable tumour size ≥20 mm, for whom radiotherapy was intended to facilitate breast-conserving surgery.

  Dataset EGAD50000002238

• RNA-Seq Profiles from the CheckMate-577 Clinical Trial

  The dataset contains RNAseq profiles of 386 patients from the CheckMate-577 (CA209-577) clinical trial whose ICF allows data deposition into a public repository. The Allprep DNA/RNA FFPE kit was used to simultaneously purify genomic DNA and total RNA from formalin-fixed, paraffin embedded (FFPE) tissue sections. RNA was analyzed using the Illumina TruSeq RNA Access method for library preparation, followed by sequencing on the Illumina NovaSeq platform with a 50bp paired-end strategy and a target read depth of 50M per sample. Fastq files are included.

  Dataset EGAD50000002394

• LongRNA_Monocytes

  This dataset consists of bulk RNA sequencing profiles generated from monocytes isolated from peripheral blood mononuclear cells (PBMCs) collected from 315 patients enrolled in the ImmunAID consortium. Each sample corresponds to a unique patient, providing a resource to investigate transcriptional variation in circulating monocytes across the cohort. PBMCs were isolated from whole blood, and monocytes were subsequently enriched using standard immunological protocols. Total RNA was extracted and libraries were prepared using the SMART-Seq mRNA Library Preparation Kit with Unique Molecular Identifiers (UMIs). Sequencing was performed on an Illumina NovaSeq 6000 platform following manufacturer-recommended protocols.

  Dataset EGAD50000002341

• Exome Sequencing to Identify Causes of Leukaemia Predisposing Congenital Neutropenias (2019-08-19)

  The objective of this study is to identify the causative genes in two unrelated congenital neutropenia families. We aim to whole exome sequence the affected individuals, unaffected siblings and parents in both cases in an effort to idenitfy the causative genetic mutation. Exome capture will be performed using Agilent SureSelect system. Subsequently, exome libraries will sequenced using the Illumina HiSeq platform. Sequence variant calling will be done in house and common variants excluded using public databases and data from unaffected family members. . This dataset contains all the data available for this study on 2019-08-19.

  Dataset EGAD00001005264

• Pediatric Papillary Thyroid Carcinoma Whole Exome Sequencing

  Exome libraries from 47 blood and tissue samples were prepared using Agilent SureSelect Human Exome Library Preparation V5 kit and the Agilent Bravo Automation System fExome libraries were pooled and sequenced with the TruSeq SBS sequencing chemistry using a V4 high throughput flowcell on a HiSeq 2500 platform following Illumina’s recommended protocol. Approximately 6-8 gigabases of raw paired end data of 126-bases were generated per exome library.

  Dataset EGAD00001007502

• RNA-seq Revision

  The dataset comprises bulk RNA‑seq libraries generated on the Illumina NextSeq 500 platform, including primary human hepatocytes (four donors), colon tissue (four masked replicates), and a comprehensive set of iPSC‑derived samples from the JHU106, ChiPSC18, ChiPSC22, and H9 lines. The collection covers multiple differentiation stages from iPSC to DE to HLC and cultivation protocols (CEL, HAY, SPH) with at least three replicates per condition. All sequencing data are provided as raw FASTQ files, with colon samples delivered as masked FASTQ in accordance with patient consent requirements.

  Dataset EGAD00001008951

• scRNAseq of ALS patients

  The data set contains information from 9 individuals (5 ALS + 4 controls) using single cell RNA sequencing in combination with TCR V(D)J sequencing to study the immune profile of the central nervous compartment (CSF). Sequencing was done using 10x Genomics platform (5’ scRNAseq & V(D)J Reagent Kits v1.1). 5P and TCR libraries were then pooled and for sequencing on the NovaSeq sequencer. Provided files are in .fastq.gz format and per individual four files are available (Read 1&2 and Lane 1&2).

  Dataset EGAD00001009623

• Whole-genome bisulfite sequencing

  Raw reads from whole-genome bisulfite sequencing. Whole-genome bisulfite sequencing library preparations and Illumina sequencing of DNA samples from TET2 mutation carriers (Ly9, Ly11, Ly14, Id1) and their age-matched controls (Ly8, Ly10, Ly13, Id2, Id3) was done as a service at BGI (BGI Tech Solutions Co., Ltd., China). Bisulfite treatment was done with EZ DNA Methylation-Gold Kit (Zymo Research, CA, USA) for 300-400bp size-range fragments with methylated adapters in 5' and 3' ends. Sequencing was done with the HiSeq X-Ten platform using paired-end 150 base-pair read length.

  Dataset EGAD00001004779

• Whole-exome ultra-high throughput sequencing in brain samples of suicide victims who had suffered from major depressive disorder and control subjects who had died from other causes

  Whole exome NGS data of 21 sucide victims and 23 control patients sequenced on Illumina HiSeq 2000 platform using the Agilent SureSelect Human All Exon + UTRs V5 target enrichment kit. The dataset contains the paired-end unfiltered FASTQ files, the GRCh37 (b37) aligned BAM files mapped by the BWA MEM algorithm, and the variant files in VCF 4.1 format called with the GATK HaploType caller (version 3.3).

  Dataset EGAD00001004184

• Human normal esophagus and Barrett's esophagus mtDNA sequencing

  BAM files containing paired-end mtDNA sequencing data from human esophageal samples of individuals that had progressed to dysplasia or developed Barrett's esophagus (BE) post-esophagectomy. BE biopsies and the background mucosa were analysed. Each patient (JE*) has associated mtDNA sequencing data from biopsies of stroma, BE and squamous and cardia tissue. Two technical replicates, denoted "A" and "B", were analysed for each biopsy. Libraries were sequenced via the Illumina MiSeq platform v2 (Illumina, San Diego, CA, USA) 300 cycles (150 nt paired-end).

  Dataset EGAD00001008310

• Whole genome sequencing on HiSeq platform of tumour-normal sample pairs from 183 melanoma cases

  Aligned, merged and deduplicated BAM files from HiSeq whole genome sequencing of 366 samples: matched tumour-normal pairs from 183 melanoma cases comprising 48 primary melanomas, 15 cell lines, and 120 metastases. Sequencing was performed on the Illumina HiSeq 2000 and Xten platforms at Australian and Korean sequencing centres. Data was aligned to the human genome (GRCh37) using BWA-MEM.

  Dataset EGAD00001003388

• The Genetic Landscape of Ocular Adnexa MALT Lymphoma Reveals Frequent Aberrations in NFAT and MEF2B Signaling Pathways

  69 OAMZL patients were sequenced on the Illumina platform. The data files are available in BAM format.

  Dataset EGAD00001011067

• Single-Cell DNA Methylation Profiling via scTAMseq

  This dataset comprises single-cell DNA methylation and nuclear genotyping profiles of 7 total bone marrow aspirates (donors A.1-A.7) and 5 CD34+-enriched bone marrow samples (donors B.1-B.5) generated using the scTAMseq protocol. Sequencing was performed on the Mission Bio Tapestri platform, targeting a panel of 448 CpGs to assess epigenetic patterns and We also included 147 genomic regions commonly mutated in clonal hematopoiesis and 20 regions targeting chromosome Y. Samples B.1 & B.5, B.2 & B.4 and A.2 & A.5 were, in pairs, multiplexed into single tapestri lanes.

  Dataset EGAD00001015498

• A Scalable, GMP-Compatible, Autologous Organotypic Cell Therapy for Dystrophic Epidermolysis Bullosa

  Gene editing in induced pluripotent stem (iPS) cells has been hailed for enabling new cell therapies for various monogenetic diseases including dystrophic epidermolysis bullosa (DEB). However, manufacturing, efficacy, and safety roadblocks have limited the development of genetically corrected, autologous iPS cell-based therapies. Dystrophic Epidermolysis Bullosa Cell Therapy (DEBCT), is a new generation, Good Manufacturing Practice-compatible (cGMP), reproducible, and scalable platform to produce autologous clinical-grade iPS cell-derived organotypic induced skin composite (iSC) grafts to treat incurable wounds of patients lacking type VII collagen (C7). DEBCT uses a single step, combined, high-efficiency reprogramming, and CRISPR-based genetic correction to generate genome scar-free, COL7A1 corrected clonal iPS cells from primary patient fibroblasts. Validated iPS cells are converted into epidermal, dermal, and melanocyte progenitors with a novel 2D organoid differentiation protocol, followed by CD49f enrichment and expansion to minimize maturation heterogeneity. iSC product characterization by single cell transcriptomics was followed by mouse xenografting for disease correcting activity at 1 month and toxicology analysis at 1-6 months. Culture-acquired mutations, potential CRISPR-off target effects, and cancer-driver variants were evaluated by targeted and whole genome sequencing. iPS cell-derived iSC grafts were reproducibly generated from four recessive DEB patients with different pathogenic mutations. Organotypic iSC grafts onto immune-compromised mice developed into stable stratified skin with functional C7 restoration. Single cell transcriptomic characterization of iSCs revealed prominent holoclone stem cell signatures in keratinocytes and the recently described Gibbin-dependent signature in dermal fibroblasts. The latter correlated with enhanced graftability. Multiple orthogonal sequencing and subsequent computational approaches identified random and non-oncogenic mutations introduced by the manufacturing process. Toxicology revealed no detectable tumors after 3-6 months in DEBCT-treated mice. In conclusion, DEBCT successfully overcomes previous roadblocks and establishes a robust, scalable, and safe cGMP manufacturing platform for the production of a CRISPR-corrected autologous organotypic skin graft to heal DEB patient wounds.

  Study phs003271

• Whole exome and RNA sequencing of organoid samples derived from TRACERx patients

  Immune checkpoint blockade in non-small cell lung cancer (NSCLC) rarely leads to complete tumour remission, suggesting that tumours harbour subpopulations of cancer cells that can escape immune predation. However, while tumours consist of multiple genetically distinct clones, the extent to which separate tumour subclones differ intrinsically in their functional capacity for immune evasion remains largely unexplored. This has been challenging to address due to an inability to isolate and propagate individual tumour subclones from human cancers. Here, we leverage the multi-region TRACERx lung cancer evolution study to generate a patient-derived platform that allows the functional analysis of immune escape at single clone resolution. We generated libraries of >20 separate NSCLC organoid lines per patient by isolating individual (clonal) organoids established from multiple spatially separated tumour regions. Each organoid subline was co-cultured with autologous tumour infiltrating lymphocytes (TIL) to evaluate their capacity to elicit a T cell response. Organoid lines derived from separate tumour regions, or from single clones within individual regions, differ vastly in their capacity to elicit a T cell response, showing the coexistence of intrinsically immune evading (‘hot’) and non-evading (‘cold’) clones in the same primary tumour. Organoid lines escaping T cell recognition represent genetically and transcriptionally unique subclones with a distinct evolutionary history, showing that evolutionary sculpting of subclonal diversity can have functional consequences for anti-tumour immunity. Notably, the identification of immune-evasive subclones would not have been possible using computational approaches alone, highlighting the unique value of functional co-culture platforms. This patient-derived functional co-culture platform reveals that tumour evolution can give rise to distinct cancer clones with intrinsic differences in immune evasion capacity and provides an approach to prospectively identify, isolate and characterise immune evading subclones from patients with cancer.

  Study EGAS00001008092

• Raw bulk TCRseq data fromTIL and non-TIL expanded TRACERx samples in the manuscript Bulk TCRseq from TRACERx samples from 'Subclonal immune evasion in non-small cell lung cancer'

  Immune checkpoint blockade in non-small cell lung cancer (NSCLC) rarely leads to complete tumour remission, suggesting that tumours harbour subpopulations of cancer cells that can escape immune predation. However, while tumours consist of multiple genetically distinct clones, the extent to which separate tumour subclones differ intrinsically in their functional capacity for immune evasion remains largely unexplored. This has been challenging to address due to an inability to isolate and propagate individual tumour subclones from human cancers. Here, we leverage the multi-region TRACERx lung cancer evolution study to generate a patient-derived platform that allows the functional analysis of immune escape at single clone resolution. We generated libraries of >20 separate NSCLC organoid lines per patient by isolating individual (clonal) organoids established from multiple spatially separated tumour regions. Each organoid subline was co-cultured with autologous tumour infiltrating lymphocytes (TIL) to evaluate their capacity to elicit a T cell response. Organoid lines derived from separate tumour regions, or from single clones within individual regions, differ vastly in their capacity to elicit a T cell response, showing the coexistence of intrinsically immune evading (‘cold) and non-evading (‘hot) clones in the same primary tumour. Organoid lines escaping T cell recognition represent genetically and transcriptionally unique subclones with a distinct evolutionary history, showing that evolutionary sculpting of subclonal diversity can have functional consequences for anti-tumour immunity. Notably, the identification of immune-evasive subclones would not have been possible using computational approaches alone, highlighting the unique value of functional co-culture platforms. This patient-derived functional co-culture platform reveals that tumour evolution can give rise to distinct cancer clones with intrinsic differences in immune evasion capacity and provides an approach to prospectively identify, isolate and characterise immune evading subclones from patients with cancer.

  Study EGAS00001008118

• In this study, blood-brain barrier (BBB)-forming brain endothelial-like cells were generated from apolipoprotein E gene allele E4 (APOE4, high AD risk) and allele E3 (APOE3, lower AD risk) carrying patient-derived induced pluripotent stem cells (iPSCs). Cells were subsequently exposed to focused ultrasound and microbubbles (FUS+MB) to induce BBB opening and their transcriptome analysed. RNA sequencing (RNA-seq) results demonstrated minimal changes in the gene expression following FUS+MB suggesting safety of FUS+MB application in the clinical setting.

  The blood-brain barrier (BBB) is a major impediment to therapeutic intracranial drug delivery for the treatment of neurodegenerative diseases, including Alzheimer’s disease (AD). Focused ultrasound applied together with microbubbles (FUS+MB) is a novel technique to transiently open the BBB and increase drug delivery. Evidence suggests that FUS+MB is safe, however the effects of FUS+MB on human BBB cells, especially in relation to AD, remain sparsely investigated. Here we developed a human sporadic AD BBB cell platform to investigate the effects of FUS+MB on BBB cells and screen for the delivery of two potentially therapeutic AD antibodies. We generated BBB cells from apolipoprotein E gene allele E4 (APOE4, high AD risk) and allele E3 (APOE3, lower AD risk) carrying patient-derived induced pluripotent stem cells (iPSCs). We utilized this robust and reproducible platform to demonstrate increased delivery of potentially therapeutic antibodies across the BBB, including an analogue of Aducanumab (AduhelmTM) following FUS+MB treatment. Our results also demonstrate the safety of FUS+MB indicated by minimal changes in the cell transcriptome as well as little or no changes in cell viability and inflammatory responses within first 24 h post FUS+MB, with potentially important implications in a clinical setting. Finally, we report a more physiologically relevant hydrogel-based 2.5D BBB model as a key development for FUS+MB-mediated drug delivery screening, with potentially higher translational utility. Our results provide an important advancement for identifying FUS+MB-deliverable drugs and screening for cell- and patient-specific effects of FUS+MB, accelerating its use as a therapy in AD.

  Study EGAS00001005944

• Single cell TCRseq data fromTIL and non-TIL expanded TRACERx samples in the manuscript Bulk TCRseq from TRACERx samples from 'Subclonal immune evasion in non-small cell lung cancer'

  Immune checkpoint blockade in non-small cell lung cancer (NSCLC) rarely leads to complete tumour remission, suggesting that tumours harbour subpopulations of cancer cells that can escape immune predation. However, while tumours consist of multiple genetically distinct clones, the extent to which separate tumour subclones differ intrinsically in their functional capacity for immune evasion remains largely unexplored. This has been challenging to address due to an inability to isolate and propagate individual tumour subclones from human cancers. Here, we leverage the multi-region TRACERx lung cancer evolution study to generate a patient-derived platform that allows the functional analysis of immune escape at single clone resolution. We generated libraries of >20 separate NSCLC organoid lines per patient by isolating individual (clonal) organoids established from multiple spatially separated tumour regions. Each organoid subline was co-cultured with autologous tumour infiltrating lymphocytes (TIL) to evaluate their capacity to elicit a T cell response. Organoid lines derived from separate tumour regions, or from single clones within individual regions, differ vastly in their capacity to elicit a T cell response, showing the coexistence of intrinsically immune evading (‘cold) and non-evading (‘hot) clones in the same primary tumour. Organoid lines escaping T cell recognition represent genetically and transcriptionally unique subclones with a distinct evolutionary history, showing that evolutionary sculpting of subclonal diversity can have functional consequences for anti-tumour immunity. Notably, the identification of immune-evasive subclones would not have been possible using computational approaches alone, highlighting the unique value of functional co-culture platforms. This patient-derived functional co-culture platform reveals that tumour evolution can give rise to distinct cancer clones with intrinsic differences in immune evasion capacity and provides an approach to prospectively identify, isolate and characterise immune evading subclones from patients with cancer.

  Study EGAS00001008161

• Rapid Acceleration of Diagnostics - Digital Health Technologies (RADx-DHT): Covidseeker and COVID-19 Citizen Science: Leveraging Citizen Science and Real-Time Geospatial Temporal Mobile Data for Digital Contact Tracing and SARS-CoV-2 Hotspotting

  The Covidseeker and COVID-19 Citizen Science Study integrates a retrospectively-determined geolocation digital program into an established digital infrastructure housed within the NIH-funded Eureka platform to enroll SARS-CoV-2 positive and negative individuals. The solution also leverages the ongoing COVID-19 Citizen Science Study cohort both in-person and remotely to test and implement existing technology to enhance readily accessible contact tracing methods and identify “hot spots” of transmission of SARS-CoV-2. The tools are designed to alert users regarding overlap with SARS-CoV-2 infected individuals, identifying businesses that were visited by someone who later tested positive for COVID-19, and working with those businesses and public health departments on strategies to reduce the spread of the virus. DOI: https://rapids.ll.mit.edu/10.57895/me7r-vp06

  Study phs002519

• National Human Genome Research Institute Tumor Sequencing Project (TSP) - Lung Adenocarcinoma

  The Tumor Sequencing Project (TSP) Consortium is a collaboration among participants at the Baylor College of Medicine Human Genome Sequencing Center, the Broad Institute Genome Sequencing Platform, the Dana Farber Cancer Institute, the Memorial Sloan-Kettering Cancer Center, the Genome Sequencing Center and Siteman Cancer Center at Washington University, the M.D. Anderson Cancer Center and the University of Michigan Medical Center. The TSP Part A will pilot approaches to large-scale identification of genomic changes in tumors by sequencing the exonic regions of 623 genes in 188 specimens of adenocarcinoma of the lung, as well as using high density SNP genotyping arrays for high resolution identification of changes in chromosomal copy number. The TSP Part B will pilot approaches to tumor characterization of lung adenocarcinoma samples using next-generation sequencing technologies and benchmark those results against Part A data generated with ABI3730 instruments.

  Study phs000144

• Rapid Acceleration of Diagnostics - Digital Health Technologies (RADx-DHT): Digital Health Solutions for COVID-19: COVID Community Action and Research Engagement (COVID-CARE)

  Vibrent Health will expand the Vibrent Digital Health Solutions Platform (DHSP) implementation to additional populations among diverse user groups for additional validation of the technology's performance, usability, and reliability in refinement of analytics generating predictive algorithms for infection and that support individual, organizational, community and societal-level decision-making in the COVID-19 pandemic response. This includes the aims to innovate a technology that can differentiate between COVID-19 and flu (or other respiratory illness); develop and test a novel WIFI-based contact tracing tool using a University’s enterprise WIFI system and software release of augmented contact tracing capabilities in Vibrent's DHSP; and develop a full technical integration approach and strategy to support data exchange between this solution and the NCI data hub.DOI: https://rapids.ll.mit.edu/10.57895/ravs-1b57

  Study phs002533

• The Nurses' Health Study (NHS) GWAS of Mammographic Density

  The Nurses' Health Study is an on-going prospective cohort study of women that was initiated in 1976. This specific study was part of a larger study to advance our knowledge of breast cancer etiology, expand the current knowledge of mammographic density, and clarify the relationship between mammographic density and breast cancer risk. We conducted a nested case control study of breast cancer among women who provided a blood sample. We then targeted our mammogram collection to participants that were selected as part of this nested case-control study (i.e. those who had provided a blood sample). The mammogram closest to the date of blood draw (~1989-1990) was used. We assessed mammographic breast density from digitized film images using a computer assisted thresholding method (Cumulus). The women in this study were genotyped using the Illumina Omni Express Platform.

  Study phs000975

• HCI-PDX Trial Center for Breast Cancer Therapy

  The HCI-PDX Trial Center for Breast Cancer Therapy study is a collection of patient-tumor samples that are serially established as patient-derived tumor xenografts (human tumor in mouse) and matching organoids. For this study, we describe valuable methods and resources to generate organoids and use them as cost-effective models for precision drug screens. This study leveraged whole-exome sequencing, RNAseq, and SNP-array data to illustrate how the heterogeneity of tumors is preserved in xenograft and organoid models. Sequencing files are provided for whole-exome and RNAseq data. Processed copy number variant calls from the SNP arrays are also available. A full description of the study can be found in the article entitled, "A human breast cancer-derived xenograft and organoid platform for drug discovery and precision oncology," written by Guillen et al., 2022 in Nature Cancer (PMID: 35221336).

  Study phs002479

• Whole Genome and Exon Capture Sequencing of Bladder Cancers

  One primary bladder cancer and paired peripheral blood sample were subjected to whole genome sequencing on an Illumina HiSeq 2000 platform. This technology was utilized to investigate the genetic basis of a durable remission of metastatic bladder cancer in a patient treated with everolimus, a drug that inhibits the mTOR (mammalian target of rapamycin) signaling pathway. Among the somatic mutations found was a loss-of-function mutation in TSC1 (Tuberous Sclerosis Complex 1), a regulator of mTOR pathway activation. Targeted sequencing using an exon capture and sequencing assay was performed on 13 tumors derived from patients on the same everolimus trial as the index patient and the sequencing data from these tumors is included. TSC1 mutation status was correlated with response to everolimus. The index patient responder tumor and peripheral blood DNA were also subjected to exon capture and sequencing.

  Study phs000535

• A Human Lymphoma Organoid Model for Evaluating and Targeting the Follicular Lymphoma Tumor Immune Microenvironment

  Heterogeneity in the tumor microenvironment (TME) of follicular lymphoma (FL) can affect clinical outcomes. We developed a new organoid culture method for cultivating patient-derived lymphoma organoids (PDLOs), which include cells from the native FL TME. We generated organoids from 12 FL patients at diagnosis, clinical progression, or relapse. These organoids were profiled with targeted DNA sequencing and mRNA sequencing. We evaluated the stability of organoids in culture at serial weekly timepoints (D0, D7, D14, D21). We treated organoids with CD19:CD3 or CD20:CD3 bispecific antibodies or unconjugated anti-CD20, anti-CD19, and anti-CD3 as a control, and profiled DNA/RNA at D11 to evaluate treatment response. This system is intended as a platform for advancing precision medicine efforts in FL through patient-specific modeling, high-throughput screening, TME signature identification, and treatment response evaluation.

  Study phs003410

• Characterization of Macrophage-Tropic HIV Infection of Central Nervous System Cells and the Influence of Inflammation

  In this study, we utilize macrophage-tropic and T cell-tropic HIV-1 Env proteins to establish accurate infection profiles for multiple CNS cells under basal and interferon alpha (IFN-α) or lipopolysaccharide (LPS)-induced inflammatory states. We found that macrophage-tropic viruses confer entry advantages in primary myeloid cells, including monocyte-derived macrophages, microglia, and induced pluripotent stem cell (iPSC)-derived microglia. Following 24-h IFN-α or LPS treatments, total RNA was harvested from 100,000 to 200,000 cells using an RNeasy RNA isolation kit (Qiagen, 74004). RNA was quantified using a NanoDrop spectrophotometer and TapeStation electrophoresis prior to library preparation. cDNA libraries were prepared using the KAPA RNA HyperPrep kit (Roche, 08098115702). Paired-end RNA sequencing was performed on a NovaSeq S4 platform at a read length of 100 bp, resulting in approximately 60 million reads per sample.

  Study phs003306

• Genetic Analysis of Skin Cells

  Cutaneous squamous cell carcinoma (cSCC) is a form of skin cancer originating from keratinocytes in the skin. They have high mutation burdens, primarily driven by UV-radiation-induced DNA damage. The order in which mutations undergo selection during the evolution of cSCC is not known. A subset of cSCCs grow out of benign neoplasms called actinic keratoses. To better understand the evolution of cSCC, we identified cases of cSCCs adjacent to actinic keratoses. From these cases, we separately microdissected the surrounding normal skin, the actinic keratosis, and the cSCC, and we performed targeted DNA-sequencing on the tissue from each area. We reconstructed tumor phylogenies and performed spatial transcriptomics on the 10X FFPE Visium platform on a subset of cases. Collectively, these studies revealed the mutational and gene expression changes that arise during the evolution of cSCC.

  Study phs003282

• Controlling cell differentiation with precision through understanding the structure and dynamics of gene regulatory networks

  We established a set of transgenic human ES cell lines that carry inducible expression gene cassette for singe transcriptional factor induction with Tet-ON system. Transcriptome data was obtained 48h after transgene induction by Microarray. We established inducible human ES lines about more than 700 genes, and achieved microarray analysis on 115 genes. Our data set has multiple characteristic properties; 1) the same platform across data set, 2) analyzed with dynamic cell status, 3) pre-determined initiation point on gene perturbation, 4)inducible in different cell status. In parallele, we also performed RNA sequenncig analysis on 435 transgene induced ES lines as well. 32 transgene induced transcriptome data were obtained from both Microarray and RNA sequencing, normalizing technical gaps between them. We hope those systematic data set to reveal transcriptional network structure and molecular mechanisms of cell differentiation.

  Study JGAS000121

• Immunogenomic analysis of tumor infiltrating B cells in gastric cancer

  Despite the accumulating evidences of the significance of humoral cancer immunity, its molecular mechanisms have largely remained elusive. This study aimed at profiling the global picture of the humoral cancer immunity in view of immune repertoire characteristics of tumor-infiltrating B cells. In this study, we investigated B-cell repertoire (BCR) / immunoglobulin (Ig) sequencing of tumor infiltrating B cells in 102 clinical gastric cancers. First, total RNAs were extracted from frozen gastric cancer tissues and corresponding normal gastric mucosa; then, BCR/Ig repertoires of tumor-infiltrating B cells were amplified by target PCR using multiplex primer sets available from iRepertoire(R), inc. Subsequent next-generation sequencing data obtained by the Illumina platform were aligned onto human BCR/Ig repertoire sequence. This dataset contains the repertoire sequencing data of 102 gastric cancer cases analyzed in this study.

  Study JGAS000242

• Validation_of_a_Haloplex_platform_for_targeted_re_sequencing_of_the_exons_of_25_genes

  We recently used the Agilent SureSelect platform to re-sequence a set of genes known to bemutated in human AML. The results from 10 AML DNA samples were very satisfactory, butthe effort required was significant.Thus, we decided to re-sequence the same genes using the Haloplax system for targetenrichment in 48 AML samples. We planned to do this using MiSeq and have data from apilot of 3 samples. The data is promising but coverage appears pathcy so far.However, in order to get a better understanding of the data we will need deeper sequencing. Wewill need two lanes of HiSeq to get the same degree coverage as Sureselect.his 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 EGAS00001000285

• Study the differences at the trascriptome level between iNKT and T cells

  Chimeric antigen receptor anti-CD19 (CAR19)-T cell immunotherapy-induced clinical remissions in CD19+ B cell lymphomas are often short-lived. We tested whether CAR19-engineering of the CD1d-restricted invariant NKT (iNKT) cells would result in enhanced anti-lymphoma activity. CAR19-iNKT cells co-operatively activated by CD1d- and CAR19-CD19-dependent interactions are more effective than CAR19-T cells against CD1d-expressing lymphomas in vitro and in vivo. The swifter in vivo anti-lymphoma activity of CAR19-iNKT cells and their enhanced ability to eradicate brain lymphomas underpinned an improved tumor-free and overall survival. CD1d transcriptional de-repression by all-trans retinoic acid results in further enhanced cytotoxicity of CAR19-iNKT cells against CD19+ chronic lymphocytic leukemia cells. Thus, iNKT cells are a highly efficient platform for CAR-based immunotherapy of lymphomas and possibly other CD1d-expressing cancers.

  Study EGAS00001003176