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• Combination therapies for personalized cancer medicine

  It is the ambition of the team formed by members of the Netherlands Cancer Institute (NKI) and the Cancer Genome Project at the Wellcome Trust Sanger Institute (WTSI) to unravel the genomic and phenotypic complexity of human cancers in order to identify optimal drug combinations for personalized cancer therapy. Our integrated approach will entail (i) deep sequencing of human tumours and cognate mouse tumours; (ii) drug screens in a 1000+ fully characterized tumour cell line panel; (iii) high-throughput in vitro and in vivo shRNA and cDNA drug resistance and enhancement screens; (iv) computational analysis of the acquired data, leading to significant response predictions; (v) rigorous validation of these predictions in genetically engineered mouse models and patient-derived xenografts. This integrated effort is expected to yield a number of combination therapies and companion-diagnostics biomarkers that will be further explored in our existing clinical trial networks.

  Dataset EGAD00001000869

• Whole Exome Sequencing for Colorectal Cancer

  This project was designed to use next generation sequencing technology to screen the protein coding regions of the genome for low frequency variants in a panel of high-risk colorectal adenocarcinoma cases. Blood and cell-line DNA for colorectal cancer patients and a subset of quality control samples that had existing whole exome sequence data were analyzed using Illumina HiSeq sequencers. Samples from this project were from participants in the Women's Health Initiative (WHI) and the Diet, Activity, and Lifestyle Study (DALS).

  Study phs000410

• Characterizing Disease-Causing Variants Using Personal Genomes with Large Recurrent Deletions

  Individuals with recurrent genomic deletions are known to present variable clinical phenotypes, despite the apparent identical range of the genomic segments being affected in their genomes. We propose to study the phenotypic variability and the molecular polymorphism in individuals with the recurrent 17q12 deletions or the recurrent 1q21.1 deletions, with the objective to establish causal relationship between the genotypes and the incompletely penetrant clinical phenotypes. Genome sequencing and phenotypic data from individuals with the deletions and their relatives are included in this submission.

  Study phs002613

• GUARDIAN: The Insulin Resistance Atherosclerosis Family Study (IRASFS)

  TThe IRAS Family Study was a family study designed to examine the genetic and epidemiologic basis of glucose homeostasis traits and abdominal adiposity. Briefly, self-reported Mexican pedigrees were recruited in San Antonio, TX and San Luis Valley, CO. Probands with large families were recruited from the initial non-family-based IRAS Study, which was modestly enriched for impaired glucose tolerance and T2D. GUARDIAN includes 1,024 individuals in 88 pedigrees from the IRAS Family Study. Insulin sensitivity was obtained by FSIGT.

  Study phs001008

• Characterization of Neoantigen-reactive T cells by Single-Cell Analysis

  Through CITE-seq and TCR-seq analysis of non-small cell lung cancer (NSCLC) tumor-infiltrating lymphocytes (TIL), we developed a neoantigen-reactive T-cell signature based on clonotype frequency and CD39 protein and CXCL13 mRNA expression. There are four datasets from four NSCLC cases. Each dataset includes (1) Transcriptome of tumor infiltrating lymphocytes (TIL), (2) Cell surface protein expression on TIL by Feature barcoding, (3) T-cell receptor analysis of TIL, and (4) Reference file for feature-barcoding antibodies.

  Study phs002792

• Breast Cancer Genome Guided Therapy Study (BEAUTY)

  The Breast Cancer Genome Guided Therapy Study (BEAUTY) is a prospective neoadjuvant clinical study enrolling 140 women with Stage I-III breast cancer. The goals of this study were to 1) perform comprehensive sequencing of germline and tumor tissues (exome and RNA seq), 2) identify genomic alterations and perturbed pathways associated with response/resistance to standard chemotherapy, and 3) develop patient-derived xenograft (PDX) for testing of therapeutic regimens chosen on the basis of alterations identified by genetic sequencing.

  Study phs001050

• CCG Multicentric Italian Lung Detection (MILD)

  For the CCG-MILD project, NCI will utilize whole genome sequencing and/or whole exome sequencing in conjunction with transcriptome sequencing to try to identify recurrent genetic alterations (mutations, deletions, amplifications, rearrangements) and/or gene expression signatures that would be important to the hypothesis(es) submitted by the investigators. The samples will be processed and submitted for genomic characterization using the established NCI Genome Characterization Pipeline. Subsequent genomic and clinical data will be hosted at the NCI Genomic Data Commons (GDC).

  Study phs002253

• Characterization of the Gut-Associated Microbiome in Inflammatory Pouch Complications Following Ileal Pouch-Anal Anastomosis

  This study involved evaluation of the tissue associated microbiome of the ileal pouch following surgery for ulcerative colitis (UC) or familial adenomatous polyposis (FAP). Individuals were recruited, with biopsies taken from the ileal pouch and the pre-pouch ileum, microbial DNA was extracted and sequenced using 454 pyrosequencing. Total bacterial community structure and abundance were evaluated to determine which changes were characteristic of inflammatory phenotypes including pouchitis (inflammation of the ileal pouch) and a Crohn's disease-like phenotype.

  Study phs000659

• Metagenomic study of the human skin microbiome associated with acne

  Acne vulgaris affects 17 million Americans, more than 80% of the people of age 12-24. The goal of this study is to investigate the relationship between acne pathogenesis and the skin microbiota residing in the microcomedones. This study will enroll approximately 100 healthy individuals and acne patients, both male and female with age 13 or older. Data obtained from this study will help better understand the disease pathogenesis and may lead to the development of new effective therapeutic strategies for treatment of acne.

  Study phs000263

• Childhood Cancer Data Initiative (CCDI): Single-Cell Atlas of NF1 Nerve Sheath Tumors

  The worst outcome of NF1 is the development of the aggressive and highly metastatic malignant peripheral nerve sheath tumors (MPNST), which transform from benign plexiform neurofibroma (PN) and lack effective treatment. In this study, we performed single-cell RNA sequencing of 63 clinically annotated NF1-associated peripheral nerve sheath tumors, including 24 PN, 34 premalignant atypical neurofibromas, and 5 MPNSTs. These results improve the ability of identifying high-risk neurofibromas and provide a unique opportunity for early detection of MPNST.

  Study phs003519