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• Whole exome sequencing in patients with ALS and concomitant FTD lacking the C9orf72 repeat expansion

  Amyotrophic lateral sclerosis (ALS) and frontotemporal dementia (FTD) are part of a clinical, pathological and genetic continuum. The purpose of the present study was to assess the mutation burden that is present in ALS and/or FTD known disease-causing genes in 54 patients (16 with available postmortem neuropathological diagnosis) with concurrent ALS and FTD (ALS/FTD) not-carrying the C9orf72 hexanucleotide repeat expansion, the most important genetic cause in both diseases.

  Study EGAS00001002439

• Comparison_of_transcriptional_response_of_induced_pluripotent_stem__iPS__cell_derived_and_monocyte_derived_macrophages_to_bacterial_lipopolysaccharide_stimulation

  In the first part of this project, we will differentiate IPS cells from 5 human donors into macrophages, and extract RNA from unstimulated and LPS stimulated macrophages to perform RNA sequencing. We will also extract RNA before and after stimulation in blood- derived macrophages from 5 additional, unrelated healthy samples. In the second part of the project, RNA-seq data will be analysed to compare LPS response of these two macrophage populations. In summary, we will perform 75bp PE RNA-seq on 20 samples (10 pre and post stimulus), on the HiSeq 2500 platform. Samples will be multiplexed at 5 samples / lane, so we will require 4 flow cells in total.This data is part of a pre-publication release. For information on the proper use of pre-publication data shared by the Wellcome Trust Sanger Institute (including details of any publication moratoria), please see http://www.sanger.ac.uk/datasharing/

  Study EGAS00001000563

• Genomic Regions Associated with Susceptibility to Barrett's Esophagus and Esophageal Adenocarcinoma in African Americans: The Cross BETRNet Admixture Study

  Differences in rates of diseases between different populations with similar environments are presumed to be secondary to variability in population frequencies of disease causing alleles. Recently admixed populations such as African Americans (AAs) provide a natural opportunity to identify disease-causing variants by examining the ancestry of long chromosomal haplotypes. Admixture mapping approach can be successful in locating genes for diseases such as EAC whose rates varies markedly between the ancestral populations. This is a case only study with 54 African American cases and also on a subset of 28 cases with high genotyping quality. We seek to identify chromosome regions that have excess European ancestry and contrasting it to excess African ancestry.

  Study phs001454

• Spatial heterogeneity of follicular lymphoma

  Follicular lymphoma (FL) is an incurable B cell malignancy characterized by advanced stage disease and a heterogeneous clinical course. Recent genomic studies have focused on profiling “single” FL biopsies over several time-points, however, multi-site sampling in solid cancers has demonstrated profound spatial intra-tumor heterogeneity (ITH) with implications for precision medicine based initiatives. This study examined the extent of spatial heterogeneity in FL by whole exome sequencing 22 synchronously removed spatially separated biopsies from 9 patients. We observed significant differences in the extent of ITH across cases, with two distinct patterns of high and low spatial heterogeneity emerging. Site-specific alterations in genes with biological, prognostic or therapeutic relevance included, TNFRSF14, PIK3CD, TNFAIP3, PTEN, EP300 and XBP1. In depth characterization of these variants using deep-sequencing techniques confirmed their discordant nature, suggesting on-going genetic diversification driving evolution after widespread tumor dissemination. There was evidence of tumors comprising multiple competing subclones, with distinct clusters of mutations demonstrating differential expansions within spatially-separated sites. For cases where spatial tumors were examined at two time-points (FL and transformation to diffuse large B cell lymphoma (DLBCL)), the degree of heterogeneity increased with transformation. Collectively, our results demonstrate that spatial ITH is prevalent in FL. The existence of site-specific aberrations suggests that a single biopsy may not be sufficient in all patients to capture the full genomic complexity present and these spatial variations need to be considered in biomarker-led clinical studies.

  Dataset EGAD00001003553

• Cross-Species Single-Cell Analysis of Pancreatic Ductal Adenocarcinoma Reveals Antigen-Presenting Cancer-Associated Fibroblasts

  Cancer-associated fibroblasts (CAFs) are major players in the progression and drug resistance of pancreatic ductal adenocarcinoma (PDAC). CAFs constitute a diverse cell population consisting of several recently described subtypes, although the extent of CAF heterogeneity has remained undefined. Here we employ single-cell RNA-sequencing to thoroughly characterize the neoplastic and tumor microenvironment content of human PDAC tumors. Six human PDAC tumor specimens from six patients were collected, and processed for single-cell RNA-sequencing analysis. Adjacent-normal pancreas tissue was also collected from two of the patients. Tumor samples were digested, and fluorescence-activated cell sorting was used to isolate viable cells. For one tumor sample, viable, CD45-negative, CD31-negative, and EpCAM-negative cells were also isolated to enrich for CAFs. The 10X Chromium platform was then used to isolate single cells for RNA-sequencing analysis. This work has demonstrated the differences in immune cell populations between adjacent-normal and tumor tissues, and identified subpopulations of epithelial cells and CAFs present in PDAC tumors. This high-throughput analysis is a resource to better understand the cell populations present in PDAC, and may ultimately aid in the development of more effective therapies for this deadly malignancy.

  Study phs001840

• Papuan_Genotyping

  By array based genotyping of indigenous individuals from different areas of Papua New Guinea, this project aims to provide the most comprehensive overview thus far of population structure and history in this part of the world. Papuans represent a key component in the current understanding of human history outside of Africa. Additionally, PNG harbours enormous cultural and linguistic diversity. Genotyping of diverse individuals, combined with previously generated whole-genome sequencing data, will allow the study of general patterns of population structure, the degree of genetic differentiation between groups, the extent of external gene flow into PNG and the genetic relationships to Australian Aboriginals.This data is part of a pre-publication release. For information on the proper use of pre-publication data shared by the Wellcome Trust Sanger Institute (including details of any publication moratoria), please see http://www.sanger.ac.uk/datasharing/

  Study EGAS00001001587

• Emirati Haploid Single-Sample-Assemblies (30 Individuals, 60 Assemblies)

  This dataset provides 27 phased diploid genome assemblies for Emirati trios, delivered in FASTA format. Assemblies were built with hifiasm (trio mode) from PacBio HiFi reads at ≥25× coverage for each parent and offspring, then scaffolded with NTLink and reference-guided merging using RagTag against CHM13v2. As part of the same program, a complementary set of single-sample diploid assemblies for 30 individuals (yielding 60 haplotypes) is being generated from deep PacBio HiFi data to expand a population-matched pangenome reference. Together, these resources capture Emirati genomic diversity and support downstream variant discovery and annotation.

  Dataset EGAD50000001753

• miRNA expression in response to LPS stimulus in macrophages

  Our lab is currently using macrophages as a model system for understanding how genetic variation modulates the response to external environmental stimulus. We want to extend this beyond regular polyadenylated RNA to small RNAs such as miRNAs. This project would cover the costs of a pilot to study miRNA response to LPS stimulus, and will be performed as part of a rotation project in the lab. We will require a small number of miRNA libraries and a single lane of MiSeq

  Dataset EGAD00001002196

• Processed RNA-seq data for clinical efficacy and biomarker analysis of neoadjuvant atezolizumab in operable urothelial carcinoma in the ABACUS trial

  ABACUS is a single arm phase 2 study that investigated 2 cycles of atezolizumab (1200mg Q3) prior to cystectomy in 95 patients with muscle invasive transitional cell cancer (T2-4N0M0). Pathological complete response (pCR) occurring in ≥20% of patients was the primary endpoint. Biomarker analysis on sequential tissue was a co-primary endpoint. This dataset includes the TPM and raw counts tables.

  Dataset EGAD00001006199

• Extended screen by deep amplicon sequencing

  The whole study comprises of two patient cohorts. Screening cohort: 40 patients of Germany; validation cohort: 40 patients from Asia. Further, bile duct and CCA cell lines have been analyzed. This dataset contains targeted DNA sequencing data of 40 tumor/normal pairs from the validation cohort plus 10 tumor/normal pairs of patients from the screening cohort for technical validation. Data was generated on Illumina HiSeq 2000 device in paired-end mode and is stored in BAM file format.

  Dataset EGAD00001011323