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• CEBP-Beta/IL-1-Beta/ TNF-alpha Feedback Loop Drives Drug Resistance to BCL2 and MDM2 Inhibitors in Monocytic Leukemia Cells

  To uncover the mechanisms of MDM2 inhibitor resistance that are mediated by IL-1, we performed RNAseq on three primary AML patient cells treated with idasanutlin in the presence or absence of IL-1β. These three leukemia samples were chosen because they exhibit high blast counts and are protected by IL-1β when treated with idasanutlin, as determined by apoptosis assay. We observed that a majority of the major p53 pathway targets remained upregulated in the presence of IL-1β. We next performed differential expressed gene (DEG) analysis following IL-1β treatment with and without idasanutlin. IL-1β treatment upregulated 3295, 1353, and 680 genes with ≥1 Log2FC, in each of the three patient samples, and a significant majority of these genes (82%, 62.4%, and 47.6%) remained upregulated in the presence of idasanutlin. Pathway analysis showed that IL-1β upregulated genes were associated with NF-κB, Interleukin-1 family signaling pathways, immune and inflammatory associated genes and myeloid maturation markers. To identify downstream targets that contribute to the protective effect of IL-1β during idasanutlin treatment, we performed DEG analysis on IL-1β + idasanutlin treatment compared to idasanutlin treatment alone. Interestingly, IL-1β induces its own expression and other pro-survival cytokines including TNF, CSF2 (GMCSF), IL-6, CSF3 (GCSF), as well as their respective receptors and/or coactivators, including IL1RL1 and multiple TNF receptors. We verified that IL-1β and TNF-α induce the upregulation of their own membrane-bound forms, their corresponding receptors, CSF2RB, and monocytic markers, as determined by flow cytometry immunophenotyping. Furthermore, IL-1β upregulated a number of pro-inflammatory chemokines, including CXCL13, CXCL2, etc. These findings highlight a pleiotropic role of IL-1β. The RNA expression of these three samples in the presence and absence of IL-1β and idasanutlin treatment will be deposited in dbGaP.

  Study phs003479

• Establishment of iPS cells from Japanese healthy volunteers

  We performed whole exome sequencing of Japanese volunteers. We established iPSCs from those volunteers, and the iPSCs were deposited to Riken Bioresource Bank. The whole exome sequencing were performed using their PBMCs.

  Study JGAS000287

• Identification of phenotype-modifier genes

  Patients were stratified at the extremes of the renal phenotype according to their estimated glomerular filtration rate annual decline and subjected to whole exome sequencing (WES) aiming to find candidate phenotype-modifier genes.

  Study EGAS50000000829

• Genome-Wide Bisulfite Sequencing of Urinary Cell-Free DNA

  The current sequencing dataset consists of 85 bisulfite sequencing data files (Fastq files) of human cell-free urine DNA samples. These extracted cfDNA samples were then constructed into DNA libraries using the KAPA HTP Library Preparation Kit (Kapa Biosystems) with bisulfite modification using the EpiTect Bisulfite Kit (Qiagen) and subsequently sequenced on the Nextseq500 platform (Illumina).

  Dataset EGAD50000001902

• RCC_HTA2.0_Reustle2022

  GeneChip HTA 2.0 data of primary renal cell carcinoma (RCC) related to Reustle et al., Clin Transl Med 12:2022 e883. Microarrays were normalized individually using the SCAN method from the R package SCAN.UPC (version 2.26.0, R version 3.6.1). Probe sets were summarized on the Entrez GeneID level using the annotation provided by BrainArray (version 23).

  Dataset EGAD00010002352

• Whole exome sequencing data of 57 matched esophageal tumor-normal pairs

  The dataset includes whole exome sequencing (WES) data on 57 matched esophageal tumor-normal pair. The Agilent Sure-Select Human All Exon V4 plus UTRs reagent was used to capture the target exons and UTRs and Illumina HiSeq 2000 instrument was used to sequence the target region with approximately 72-fold coverage.

  Dataset EGAD00001004542

• RNA_Seq_OMELib__Cord_blood_

  The transcriptional landscape of haematopoietic cells will be characterized by RNA Seq following amplification of RNA/cDNA and preparation of libraries by PTA(primary template-directed amplification). Samples have been sourced from the Cambridge Biobank.

  Study EGAS00001007454

• Congenital anosmia 2

  Congenital anosmias can be complete (the lack of a sense of smell) or specific (the inability to detect specific smells). Here we obtained genomic DNA from families with multiple individuals with anosmia, suggesting they are congenital. These include those inherited in a manner consistent with dominant and recessive alleles. We have sequenced the exomes of both affected and unaffected family members on the Illumina platform.

  Dataset EGAD00001002228

• Shallow whole genome sequencing on stage 1 epithelial ovarian cancer

  BAM files (aligned against the hg38 genome) from a shallow whole-genome sequencing experiment (median depth 0.5X) on 218 samples from Stage 1 epithelial ovarian cancer biopises. Samples labeled "bis" or "tris" with the same ID are relapses; "left" or "right" samples indicate, in the case of bilateral tumor, from which ovary the sample was taken.

  Dataset EGAD00001006881

• Targeted sequencing of Burkitt lymphoma tumour samples from the UK's Haematological Malignancy Research Network

  Targeted sequencing was applied to an unselected population-based Burkitt lymphoma cohort (n=39) diagnosed in the UK's Haematological Malignancy Research Network catchment population of ~4 million (14 centres). DNA extracted from tumour samples was sequenced with a 293-gene panel using the Illumina HiSeq 2500. All data are provided in the CRAM format.

  Dataset EGAD00001007658