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• Uni_Wue_Chair of Microbiology

  Dual RNA seq datasets of M2 sequenced macrophages after chlamydia infection for 30 hours.

  Dac EGAC50000000577

• South African Blood Regulatory (SABR) Resource Committee

  Data access committee for the South African Blood Regulatory (SABR) Resource.

  Dac EGAC50000000501

• OICR-DAC, Ontario Institute for Cancer Research; Biliary Tract Cancer

  Next Gen Sequencing data from Biliary Tract Cancers

  Dac EGAC50000000528

• Oncogenic and immunological targets for matched therapy of pediatric blood cancer patients: Dutch iTHER study experience

  Study EGAS00001008218

• DAC for "Establishment and characterization of circulating tumor cells-derived organoids from metastatic breast cancer patients."

  Dac EGAC00001003514

• Methylation data for Genomic landscapes of endometrioid and mucinous ovarian cancers and morphologically similar tumor types

  Study EGAS00001008175

• Breast Cancer Association Consortium Data Access Coordinating Committee

  Data access committee for the Breast Cancer Association Consortium (BCAC).

  Dac EGAC50000000824

• The INFORM Precision Medicine Study for High-Risk Pediatric Malignancies

  Study EGAS00001005112

• The genomic diversity of Taiwanese Austronesian groups: implications for the ‘Into and Out of Taiwan’ models

  Study EGAS00001006911

• GFD viral enrichment sequencing

  sequencing of libraires enriched for viral particles

  Dataset EGAD00001007638

• CLUC complete genomics dataset

  Complete genomics data for VCaP and PC346c.

  Dataset EGAD00001002069

• Genome Wide Association for Asthma and Lung Function

  The SNP Typing for Association with Multiple Phenotypes from Existing Epidemiologic (STAMPEED) asthma project includes subjects with asthma and controls from the Chicago Asthma Genetics Study (CAG), NHLBI multicenter Severe Asthma Research Program (SARP) and NHLBI Collaborative Studies on the Genetics of Asthma CSGA (Wake Forest). All studies included European American and African American children and adults with asthma ranging from mild to severe and adult controls. CAG participants were collected at the University of Chicago. SARP participants were recruited at the NHLBI SARP sites with an emphasis on recruiting severe asthmatics (Moore et al, Am J Respir Crit Care Med, 2010, PMID: 19892860). CSGA cases and controls collected by the Wake Forest investigators were also included. Asthma status was based on both a physician's diagnosis and either bronchodilator reversibility or hyper-responsiveness to methacholine as well as less than 5 pack years of smoking. Genotyping was performed on the Illumina 1Mv1 platform, with individual genotypes called using clustering algorithms as implemented in the BeadStudio software by Illumina. The total number of markers following standard QC was 1,025,129. Imputation was performed using the HapMap phase 2, release 21 SNPs using MACH with the phased HapMap CEU and YRI haplotypes as a reference. Case/control association tests for asthma status were performed using logistic regression in R (http://CRAN.R-project.org/) on genotype dosages, and adjusting for the first principal component from EIGENSTRAT.

  Study phs000355

• Spatial transcriptomic data of breast cancer

  Fastq files from spatial transcriptomic of breast cancer coming from 8 Breast cancer sections. Sample preparation: frozen BC samples were chosen based on tissue structure and RNA quality (RIN > 8). The “Visium Spatial Tissue Optimization Slide and Reagent Kit” (10X Genomics; #PN-1000193) was then used to optimize permeabilization conditions for BC tissues. Briefly, sections were fixed, stained and then permeabilized at different time points to capture mRNA, and the reverse transcription was performed to generate fluorescently labeled cDNA. The permeabilization time that resulted in the highest fluorescence signal with the lowest background diffusion was chosen. The best permeabilization time for BC tissue was 18 min. Cryostat sections of 10 μm of thickness were cut and placed on Visium Spatial Gene Expression slides (10X Genomics, PN-1000184). The slide was incubated for 1 min at 37°C, then fixed with methanol for 30 min at -20°C followed by Hematoxylin and Eosin (H&E) staining and images were taken under a high-resolution microscope. After imaging, the coverslip was detached by holding the slide in water and the slide was mounted in a plastic slide cassette. The spatial gene expression process, including tissue permeabilization, second strand synthesis and cDNA amplification, was performed according to the manufacturer’s instructions (10X Genomics; #CG000239). cDNA quality was next assessed using Agilent High sensitivity DNA Kit (Agilent, #5067-4626). The spatial gene libraries were constructed using Visium Spatial Library Construction Kit (10X Genomics, PN-1000184).

  Dataset EGAD50000000322

• Genetic Basis of Pulmonary Non-tuberculous Mycobacterial Infections

  This project aims at characterizing the human host susceptibility to pulmonary non-tuberculous mycobacterial (PNTM) infections. PNTM infections occur in patients with chronic lung disease, but also in a distinct group of elderly women without lung defects but who share a common body morphology: tall and lean with scoliosis, pectus excavatum, and mitral valve prolapse. We performed whole exome and genome sequencing in extended families of patients with active PNTM. This unique collection of familial cohorts in PNTM represents an important opportunity for a high yield search for genes that regulate mucosal immunity. We also sequenced the genome of mycobacterial isolates from PNTM patients to integrate host PNTM susceptibility with mycobacterial genotypes and gain insights into the key factors involved in this devastating disease.

  Study phs000719

• The mutational characterization of adenoid cystic carcinoma

  Adenoid cystic carcinoma (ACC) typically emanate from the major and minor salivary glands of the head and neck. ACCs have high rates of perineural invasion, locoregional recurrence, and distant metastasis. Here we report sequencing of 60 tumor/normal pairs and find substantial mutational diversity. On pathway analysis, a significant percentage of mutations involved chromatin remodeling, DNA damage, protein kinase A signaling, and FGF/IGF/PI3K signaling. Whole genome sequencing and FISH confirmed the MYB-NFIB translocation as the main structural variant in ACC. Evaluation of potential driver mutations KDM6A and PIK3CA reveal that specific, observed alterations impart functional consequences. Collectively, our data delineate the ACC mutational landscape and establish a molecular foundation for investigating new therapies for this disease.

  Study phs000612

• Identification of Genomic Markers of Cervical Dystonia and Subtypes

  As the third most common movement disorder, dystonias collectively affect more than 2 million people worldwide. Despite their high prevalence, their biological roots are largely unknown. Genetic influences are suggested in familial studies, however, no specific genetic variants are responsible for a significant proportion of identified cases. Previous genome-wide association studies of the dystonias were limited by smaller sample size and lack of coverage of rare variants. In this study, we use a high-throughput genomic approach to effectively investigate relationships between over genome-wide genetic variations and dystonias. We conduct targeted analyses of candidate genes, as well as agnostic searches for any genomic with the dystonias and subtypes in a large sample of dystonia patients available.

  Study phs001803

• Natural Genetic Variation in the Human Genome

  In this study, we used existing whole genome sequencing data from the TOPMed Amish and Jackson Heart Study, as well as the GTEx study, to identify mobile element insertions in the genomes of these individuals.  A total of 1112 TOPMed Amish, 3331 TOPMed Jackson Heart Study, and 698 GTEx individuals were examined.  We used the Mobile Element Locator Tool (MELT) developed previously by our lab, along with a Cloud-based version of MELT (CloudMELT), to discover non-reference mobile element insertions (MEIs) in these genomes.  We discovered Alu, L1, SVA, and HERV-K MEIs and produced genotypes in individual genomes.  Build hg19 bams were used for the TOPMed samples, and build GRCh37 bams were used for the GTEx samples in this study.

  Study phs002463

• DirectHRD Enables Sensitive Scar-Based Classification of Homologous Recombination Deficiency (HRD)

  Homologous recombination deficiency (HRD)-induced genomic scars are an FDA-approved biomarker for identifying cancers likely to respond to PARP inhibitors. However, detecting HRD scars from blood biopsies has been challenging due to the low tumor content in blood samples. To address this limitation, we developed DirectHRD, a genomic scar-based HRD classifier leveraging whole-genome sequencing (WGS) data for non-invasive blood biopsy testing. DirectHRD was applied to 90 cell-free DNA (cfDNA) samples across four cancer types: breast, ovarian, prostate, and pancreatic. The method achieved an AUC of 0.87 and demonstrated the ability to detect HRD at tumor fractions as low as 1%, offering a tenfold increase in sensitivity compared to state-of-the-art methods.

  Study phs003760

• Ultrasensitive Detection and Monitoring of Circulating Tumor DNA using Structural Variants in Early-Stage Breast Cancer

  Circulating tumor DNA (ctDNA) detection has an emerging role in the management of breast cancer, offering a non-invasive means to monitor disease status and detect recurrence. This study demonstrates that longitudinal monitoring of tumor-specific structural variants - frequent alterations observed across many tumor types including all subtypes of breast cancer derived from Whole Genome Sequencing data - allows for ctDNA detection in nearly all participants in this cohort with untreated early breast cancer prior to starting neoadjuvant therapy. On-treatment ctDNA monitoring enabled the early identification of patients at high risk of recurrence and ctDNA was detected prior to relapse in participants across all receptor subtypes. These findings demonstrate the clinical validity of this assay approach for ultrasensitive ctDNA monitoring.

  Study EGAS50000000799

• DCIS Whole Exome & Whole Genome Sequencing Data

  Primary DCIS and recurrent DCIS/IBC (total n=82, ipsilateral n=78 and contralateral n=4) as well as non-recurrent DCIS (n=32) cases were identified through hospital databases from Royal Melbourne Hospital (RMH), Nottingham City Hospital (UK), the LifePool cohort and Peter MacCallum Cancer Centre (PMCC). All cases were micro-dissected from haematoxylin stained sections (range 4-20 sections) by manual micro-dissection to achieve >50% tumour tissue purity. DNA was extracted using the FFPE AllPrep kit (Qiagen, MD, USA). Depending on the success and timing of DNA extraction (Figure 1), cases were analysed by a targeted sequencing panel (n=46, samples pre-2020), whole exome sequencing (WES, n=67), or low-coverage whole genome sequencing (LCWGS). WES: DNA was processed by the Australian Genome Research Facility (AGRF) using the Twist Bioscience Human Comprehensive Exome v1 or v2 (Twist Bioscience HQ, South San Francisco, CA, USA) according to the Twist Target Enrichment Standard Hybridisation Protocol. Sequencing was performed on the Illumina NovaSeq 6000 with 150 bp paired-end reads for a median depth of 101.29x, range: 20.39-247x. Whole Genome Sequencing (WGS): Libraries for four paired samples with matched stromal DNA were made, processed and sequenced by AGRF using the IDT xGen Kit (USA) according to the manufacturer’s protocol, aiming to achieve 60x depth for tumour DNA and 30x for matched normal. File type: Paired-end FASTQ.

  Dataset EGAD50000001846

• Single cell transcriptomics to characterize the tumor microenvironment of prostate cancer fusion biopsies

  The primary objective of this study was to characterize the tumor microenvironment in fusion-guided transperineal biopsy samples from patients undergoing PC diagnosis. For each patient, one biopsy was taken from a suspected tumor region and another from a non-suspicious area, which were later classified as high- or low-tumorigenicity based on anatomopathological analysis. Using scRNA-seq data, we performed cancer-oriented cell annotation, differential expression analysis, and functional pathway enrichment studies across key cellular subpopulations. Additionally, differential abundance analysis was conducted to identify cell groups representative of different tumorigenicity levels. Finally, classification models were developed using gene expression data to differentiate high- vs. low-tumorigenicity samples, with the long-term goal of establishing a diagnostic classifier for PC stratification.

  Study EGAS50000000888

• Whole-exome sequencing identifies new pathogenic germline variants in patients with colorectal polyposis

  Adenomatous polyposis confers an increased risk of colorectal cancer development. Here, we investigated probably underlying predisposition variants in patients with suspected colorectal polyposis without variants in APC and MUTYH genes by whole exome sequencing (WES). Twenty-seven patients were included and subjected to germline WES. After filtering out variants for sequencing quality, variant allele fraction frequency, and population frequency, variants were manually prioritized by the ACMG criteria. Among the variants identified, 17 were classified as pathogenic or likely pathogenic (in 12 patients). This study gives information of probably associated polyposis variants in Brazilian patients without germline pathogenic variants in APC and MUTYH genes, supporting the utilization of next-generation sequencing for screening in these patients beyond these genes.

  Study EGAS50000000591

• Association studies using the Metabochip array - Samples analysed by the WTCCC (1958 British Birth Cohort (58BC), Hypertension cohort (HT), Type 2 Diabetes Cohort (T2D) and Coronary Artery Disease (CAD) cohort)

  Genomewide association studies (GWAS) have proven a powerful hypothesis-free method to identify common disease-associated variants. Even quite large GWAS, however, have only at best identified moderate proportions of the genetic variants contributing to disease heritability. To provide cost-effective genotyping of common and rare variants to map the remaining heritability and to fine-map established loci, the Metabochip Consortium has developed a 200,000 SNP chip that has been produced in very large numbers for a fraction of the cost of GWAS chips. This chip provides a powerful tool for genetic studies of metabolic, cardiovascular and anthropometric traits (Voight et al., in press PLoS Genetics).

  Study EGAS00000000115

• Sampling of multi-centric lower grade glioma influences management and provides insight into gliomagenesis

  Rare multicentric lower-grade gliomas (LGG) represent a unique opportunity to study the heterogeneity between distinct tumor foci in a single patient, and to infer their origins and parallel patterns of evolution. In this study, we integrate clinical features, histology and immunohistochemistry for 4 patients with multicentric LGG, arising both synchronously and metachronously. For 3 patients we analyze the phylogeny of the lesions using exome sequencing, including one case with a total of 8 samples from the two lesions. We show that each tumor in multicentric LGG cases may arise independently or may diverge very early in their development, presenting as genetically and histologically distinct tumors suggesting that comprehensive sampling of these lesions can significantly alter diagnosis and management.

  Study EGAS00001002495

• GM adipose tissue study

  The Greek Metabolic (GM) adipose study was carried out in 106 individuals living in Greece and consists of genotyping data (chip), RNA-Seq and ATAC-Seq (for a subset of individuals) data from paired biopsies of Subcutaneous and Visceral adipose tissue. eQTL mapping was performed to study gene regulation and findings compared to those from adipose tissue GTEX data. The focus of this project was to study an underexplored population living in different environmental conditions in order to reveal novel regulatory effects for genes that shape complex traits and disease risk. Our results highlight the utility of modest-sized studies in adding to our understanding of the molecular basis of complex traits and to the identification of mechanisms that drive disease in specific tissues.

  Study EGAS00001007126