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• Fecal microbiome of T2D patients undergoing semaglutide or empagliflozin treatment

  The gut microbiome has been shown to be affected by the use of many human-targeted medications, and the interaction can be bidirectional. This has been clearly demonstrated for type 2 diabetes medications that have been in clinical use for several decades. However, the bidirectional effects of novel type 2 diabetes drugs semaglutide, empagliflozin, and the gut microbiome have yet to be clearly described. We investigated the effect of semaglutide and empagliflozin initiation on the gut microbiome of type 2 diabetes patients. In addition, we analyzed whether the pre-treatment gut microbiome can predict the treatment efficacy. Twenty subjects (10 women and 10 men) were enrolled in the study between November 2019 and January 2023 from the University of Tartu Hospital, Tartu, Estonia. All participants had been diagnosed with type 2 diabetes. The study group taking semaglutide included 6 women and 4 men, and the group prescribed empagliflozin included 4 women and 6 men. Gut microbiome fecal samples donated at four timepoints (Baseline, Month 1, Month 3; Month 12) were studied using 16S ribosomal RNA gene sequencing and analysis.

  Dataset EGAD50000000756

• Proteomic predictors of individualized nutrient-specific insulin secretion in health and disease

  Population level variation and molecular mechanisms behind insulin secretion in response to carbohydrate, protein, and fat remain uncharacterized despite ramifications for personalized nutrition. We now define prototypical insulin secretion dynamics in response to the three macronutrients in islets from 140 cadaveric donors, including those diagnosed with type 2 diabetes. We leverage the insulin response heterogeneity and use transcriptomics and proteomics to identify molecular pathways of specific nutrient responsiveness. Surprisingly, we find robust insulin secretion to fatty acid stimulus in ~8% of donors, challenging the idea that fat has negligible effects on insulin release. Distinct islet proteomes with differences in metabolic signalling networks convey this hyper-responsiveness to fat relative to carbohydrate. By comparing human islets to human embryonic stem cell-derived islet clusters, we show that, unlike glucose-responsiveness, fat hyper-responsiveness is equivalent and may be a hallmark of functionally immature cells. Our study represents the first comparison of dynamic responses to nutrients and multi-omics analysis in human insulin secreting cells. Responses of different people’s islets to carbohydrate, protein, and fat lay the groundwork for personalized nutrition.

  Dataset EGAD50000000519

• RNA sequencing data of pediatric T-cell acute lymphoblastic leukemia

  T-cell acute lymphoblastic leukemia (T-ALL) is an aggressive hematologic malignancy accounting for approximately 15–25% of pediatric and adult ALL cases. Despite significant therapeutic improvements over the last decade, the prognosis of T-ALL remains less favorable than that of B-ALL, with 5-year EFS and OS of around 76–82% and 80–88%, respectively, depending on the treatment protocol used. T-ALL patients often suffer from failure of induction therapy or early relapse, which is associated with a dismal prognosis. Approximately 10–15% of T-ALL patients experience relapse, and survival after relapse is poor.

  Study EGAS50000001800

• Paired DNA and RNA sequencing uncovers common and rare genomic variants regulating gene expression in the human retina

  In this study, we uncovered common and rare genomic variants shaping retinal expression profiles. This includes 1,483,595 significant cis-expression quantitative trait loci (eQTLs) impacting 9,959 and 3,699 genes in NSR and RPE, respectively, with associated genomic variants enriched to cis-candidate regulatory elements and notable shared eGenes between NSR and RPE. We also detected 1051 expression outliers and prioritised 299 rare non-coding single-nucleotide, structural variants or copy number variants as plausible drivers for 28% of outlier events. This study increases understanding of gene expression regulation in the human retina.

  Study EGAS50000001443

• Lethal malformation syndrome

  Identification of the genetic basis of rare monogenic diseases can provide insights into disease mechanisms, biological pathways and potential therapeutic targets. Exome sequencing has proven to be a powerful, efficient strategy for the identification of the genes underlying rare Mendelian disorders. The genetic defect behind the lethal malformation syndrome under study is known in some cases and has proven useful in revealing the primary underlying defect. We have six typical unrelated families with no known mutation. The aim of this study is to identify the locus associated with this lethal malformation syndrome in these families using exome sequencing.

  Study EGAS00001000061

• Whole genome and whole transcriptome sequencing of patients diagnosed with angiosarcoma.

  Angiosarcomas are rare, clinically-aggressive tumors with a predilection for the elderly and immunosuppressed, which has incited suspicion of an oncogenic virus. We studied the metagenomic landscape of angiosarcomas and identified reads mapping to human herpesvirus-7 (HHV-7). Overall, HHV-7 was present in two-thirds of angiosarcomas, particularly in cases with low tumor mutation burden and lacking signatures of ultraviolet-induced DNA damage. Transcriptomic profiling revealed the enrichment of tumor inflammation signatures in HHV7-positive angiosarcomas. In conclusion, we identified a distinct “inflammatory” subtype of angiosarcoma associated with HHV-7.

  Study EGAS00001003895

• Leucocyte eQTLs in autoimmune disease and health

  Peripheral blood was taken from healthy controls and patients with active autoimmune disease. CD4 T cells, CD8 T cells, monocytes, neutrophils, and B cells were separated using magnetic-activated cell sorting. RNA and genomic DNA was extracted from cell lysates using Qiagen Allprep kits. Genotyping of healthy controls and patients with inflammatory bowel disease was performed using the Illumina Human OmniExpress12v1.0 BeadChip at the Wellcome Trust Sanger Institute. 200 ng RNA was processed for hybridization onto Affymetrix Human Gene ST 1.1 microarrays. Gene expression and genotyping data was used to perform eQTL mapping.

  Study EGAS00001001251

• Single cell transcriptomic and genomic profiling of carcinogenesis in patients with familial adenomatous polyposis

  Familial Adenomatous Polyposis (FAP) is characterized by hundreds to thousands of adenocarcinomas at different evolutional stages in the colon and rectum. Much effort has been made to illuminate the key genomic alterations that facilitate the transition from adenoma to carcinoma. However, the strong heterogeneity of the tumors may hamper these efforts. Here, by sequencing matched adjacent normal tissues, adenomas at different stages and carcinomas from the same patient, we precisely traced the process of colorectal carcinogenesis. Our study offers an accurate genomic landscape during the initiation and progression of carcinogenesis, especially for the transition between adenomas and carcinomas.

  Study EGAS00001003598

• Methylation_changes_in_OA_patients_with_chronic_exposure_to_cobalt_and_chromium

  We have whole blood from a population of 70 patients, half exposed chronically to an excessof metals cobalt and chromium. The 2 groups are age, sex, and OA diagnosis matched. The2 groups have systemic differences in bone mass and turnover, and other systemicdifferences.We will type the cohort of 70 individuals on the Illumina 450k methylation array and willcompare between the two groups.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 EGAS00001001180

• TMD_AMKL_targeted_follow_up

  Genomic libraries will be generated from total genomic DNA derived from 200+ patients with childhood Transient Myeloproliferative Disorder (TMD) and or Acute Megakaryocytic Leukemia (AMKL) as well some matched constitutional samples (n < 50). Libraries will be enriched for a selected panel of genes using a bespoke pulldown protocol. 96 Samples will be individually barcoded and subjected to up to two lanes of Illumina HiSeq. Paired reads will be mapped to build 37 of the human reference genome to facilitate the characterisation of known gene mutations in cancer as well as the validation of potentially novel variants identified by prior exome sequencing.

  Study EGAS00001000569