316
views
0
recommends
+1 Recommend
1 collections
    0
    shares
      • Record: found
      • Abstract: found
      • Article: found

      DNA methylation-based classification of central nervous system tumours

      research-article
      1 , 2 , 3 , 4 , 5 , 6 , 5 , 6 , 7 , 8 , 1 , 2 , 5 , 6 , 9 , 1 , 2 , 1 , 2 , 5 , 6 , 1 , 2 , 1 , 2 , 1 , 2 , 1 , 2 , 5 , 6 , 9 , 1 , 3 , 1 , 2 , 10 , 11 , 12 , 2 , 13 , 13 , 13 , 14 , 14 , 15 , 15 , 16 , 17 , 17 , 17 , 18 , 18 , 19 , 20 , 21 , 21 , 22 , 23 , 5 , 9 , 24 , 5 , 6 , 9 , 5 , 8 , 9 , 24 , 5 , 8 , 9 , 24 , 25 , 26 , 27 , 28 , 29 , 30 , 31 , 32 , 33 , 34 , 35 , 36 , 37 , 37 , 38 , 39 , 39 , 40 , 40 , 40 , 41 , 42 , 43 , 43 , 43 , 44 , 45 , 46 , 47 , 48 , 49 , 50 , 51 , 52 , 53 , 5 , 9 , 54 , 3 , 55 , 3 , 56 , 57 , 58 , 59 , 60 , 19 , 61 , 7 , 8 , 62 , 63 , 64 , 65 , 66 , 67 , 68 , 65 , 68 , 69 , 69 , 22 , 22 , 70 , 71 , 72 , 73 , 74 , 8 , 32 , 32 , 75 , 76 , 77 , 78 , 79 , 80 , 81 , 15 , 82 , 83 , 84 , 85 , 86 , 46 , 87 , 87 , 88 , 89 , 90 , 91 , 92 , 29 , 93 , 94 , 13 , 95 , 14 , 96 , 97 , 12 , 98 , 99 , 15 , 100 , 8 , 5 , 6 , 29 , 101 , 46 , 102 , 89 , 1 , 2 , 1 , 2 , 5 , 6 , 9
      Nature

      Read this article at

      ScienceOpenPublisherPMC
      Bookmark
          There is no author summary for this article yet. Authors can add summaries to their articles on ScienceOpen to make them more accessible to a non-specialist audience.

          Summary

          Accurate pathological diagnosis is crucial for optimal management of cancer patients. For the ~100 known central nervous system (CNS) tumour entities, standardization of the diagnostic process has been shown to be particularly challenging - with substantial inter-observer variability in the histopathological diagnosis of many tumour types. We herein present the development of a comprehensive approach for DNA methylation-based CNS tumour classification across all entities and age groups, and demonstrate its application in a routine diagnostic setting. We show that availability of this method may have substantial impact on diagnostic precision compared with standard methods, resulting in a change of diagnosis in up to 12% of prospective cases. For broader accessibility we have designed a free online classifier tool ( www.molecularneuropathology.org) requiring no additional onsite data processing. Our results provide a blueprint for the generation of machine learning-based tumour classifiers across other cancer entities, with the potential to fundamentally transform tumour pathology.

          Related collections

          Most cited references46

          • Record: found
          • Abstract: not found
          • Article: not found

          Regularization Paths for Generalized Linear Models via Coordinate Descent

            Bookmark
            • Record: found
            • Abstract: found
            • Article: not found

            Minfi: a flexible and comprehensive Bioconductor package for the analysis of Infinium DNA methylation microarrays.

            The recently released Infinium HumanMethylation450 array (the '450k' array) provides a high-throughput assay to quantify DNA methylation (DNAm) at ∼450 000 loci across a range of genomic features. Although less comprehensive than high-throughput sequencing-based techniques, this product is more cost-effective and promises to be the most widely used DNAm high-throughput measurement technology over the next several years. Here we describe a suite of computational tools that incorporate state-of-the-art statistical techniques for the analysis of DNAm data. The software is structured to easily adapt to future versions of the technology. We include methods for preprocessing, quality assessment and detection of differentially methylated regions from the kilobase to the megabase scale. We show how our software provides a powerful and flexible development platform for future methods. We also illustrate how our methods empower the technology to make discoveries previously thought to be possible only with sequencing-based methods. http://bioconductor.org/packages/release/bioc/html/minfi.html. khansen@jhsph.edu; rafa@jimmy.harvard.edu Supplementary data are available at Bioinformatics online.
              Bookmark
              • Record: found
              • Abstract: found
              • Article: not found

              Orchestrating high-throughput genomic analysis with Bioconductor.

              Bioconductor is an open-source, open-development software project for the analysis and comprehension of high-throughput data in genomics and molecular biology. The project aims to enable interdisciplinary research, collaboration and rapid development of scientific software. Based on the statistical programming language R, Bioconductor comprises 934 interoperable packages contributed by a large, diverse community of scientists. Packages cover a range of bioinformatic and statistical applications. They undergo formal initial review and continuous automated testing. We present an overview for prospective users and contributors.
                Bookmark

                Author and article information

                Journal
                0410462
                6011
                Nature
                Nature
                Nature
                0028-0836
                1476-4687
                1 July 2018
                14 March 2018
                22 March 2018
                14 September 2018
                : 555
                : 7697
                : 469-474
                Affiliations
                [1 ]Department of Neuropathology, University Hospital Heidelberg, Heidelberg, Germany
                [2 ]Clinical Cooperation Unit Neuropathology, German Cancer Consortium (DKTK), German Cancer Research Center (DKFZ), Heidelberg, Germany
                [3 ]Charité – Universitätsmedizin Berlin, corporate member of Freie Universität Berlin, Humboldt-Universität zu Berlin, and Berlin Institute of Health, Department of Neuropathology
                [4 ]German Cancer Consortium (DKTK), Partner Site Berlin, German Cancer Research Center (DKFZ) Heidelberg, Germany
                [5 ]Hopp Children´s Cancer Center at the NCT Heidelberg (KiTZ), Heidelberg, Germany
                [6 ]Division of Pediatric Neurooncology, German Cancer Consortium (DKTK), German Cancer Research Center (DKFZ), Heidelberg, Germany
                [7 ]Division of Biostatistics, German Cancer Research Center (DKFZ), Heidelberg, Germany
                [8 ]Division of Molecular Genetics, German Cancer Research Center (DKFZ), Heidelberg, Germany
                [9 ]Department of Pediatric Oncology, Hematology and Immunology, University Hospital Heidelberg, Heidelberg, Germany
                [10 ]Departments of Pathology and Laboratory Medicine & Neurosurgery, Medical University of South Carolina, Hollings Cancer Center, Charleston, SC, 29425, USA
                [11 ]Department of Oncology and Hematology with Sections Bone Marrow Transplant and Pneumology, Hubertus Wald Tumorzentrum / University Cancer Center Hamburg, University Medical Center Hamburg, Hamburg, Germany
                [12 ]Center for Neuropathology and Prion Research, Ludwig-Maximilians-University, Munich, Germany
                [13 ]Institute of Neurology (Edinger Institute), Goethe-University Frankfurt and German Cancer Consortium (DKTK), Partner Site Frankfurt/Mainz, Frankfurt am Main, German Cancer Research Center (DKFZ) Heidelberg, Germany
                [14 ]Institute of Neuropathology, University of Giessen, Giessen, Germany
                [15 ]Neuropathological Institute, University Hospitals Erlangen, Friedrich Alexander University Erlangen-Nuremberg, Germany
                [16 ]Institute of Pathology, University of Bern, Bern, Switzerland
                [17 ]Genomics and Proteomics Core Facility, German Cancer Research Center (DKFZ), Heidelberg, Germany
                [18 ]Institute of Pathology and Neuropathology, Department of Neuropathology, University Hospital Tübingen, Tübingen, Germany
                [19 ]Institute of Neuropathology, Medical Center – University of Freiburg, Faculty of Medicine, University of Freiburg, Germany
                [20 ]Department of Translational Molecular Pathology, University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA
                [21 ]Department of Neuropathology, Centre Hospitalier Sainte Anne, Paris, France
                [22 ]Pediatrics III, Pediatric Oncology and Hematology, University Hospital Essen, Essen, Germany
                [23 ]Eye Cancer Research Group, Faculty of Medicine, University of Duisburg-Essen, Essen, Germany
                [24 ]CCU Pediatric Oncology (G340) German Cancer Research Center (DKFZ) and German Cancer Consortium (DKTK), Heidelberg, Germany
                [25 ]Department of (Neuro)Pathology, Academic Medisch Centrum (AMC) and Swammerdam Institute for Life Sciences, Center for Neuroscience, University of Amsterdam; Stichting Epilepsie Instellingen Nederland (SEIN), The Netherlands
                [26 ]Department of Radiological, Oncological and Anatomo-Pathological Sciences, Sapienza University, Rome, Italy and IRCCS Neuromed, Pozzilli (Is), Italy
                [27 ]Department of Neuropathology, University Hospital Zurich, Zurich, Switzerland
                [28 ]Cnopf’sche Kinderklinik Nuremberg, Nuremberg, Germany
                [29 ]Department of Neurosurgery, Heidelberg University Hospital, Heidelberg, Germany
                [30 ]Hubrecht Institute-KNAW (Royal Netherlands Academy of Arts and Sciences), Uppsalalaan 8, 3584 CT Utrecht, Netherlands
                [31 ]Division of Neuropathology of the Johns Hopkins University School of Medicine, Baltimore, MD, USA
                [32 ]Department of Neuropathology, University of Bonn, Bonn, Germany
                [33 ]Department of Medicine I, Comprehensive Cancer Center Vienna, CNS Unit (CCC-CNS), Medical University of Vienna, Vienna, Austria
                [34 ]Institute of Neurology, Medical University of Vienna, Vienna, Austria
                [35 ]Department of Biomedicine, University of Bergen, Bergen, Norway
                [36 ]NORLUX Neuro-Oncology Laboratory, Department of Oncology, Luxembourg Institute of Health, Luxembourg.
                [37 ]Department of Neuropathology, Beaumont Hospital, Dublin, Ireland
                [38 ]Department of Neuropathology, University Hospital of Cologne, Cologne, Germany
                [39 ]Department of Neuropathology, Institute of Pathology, Basel University Hospital, Basel, Switzerland
                [40 ]NYU Langone Medical Center, New York, NY, USA
                [41 ]Institute of Neuropathology, University Medical Center Göttingen, Göttingen, Germany
                [42 ]Division of Oncology, Luzerner Kantonsspital, Luzern, Switzerland
                [43 ]Department of Neurosurgery, University Medical Center Mannheim, University of Heidelberg
                [44 ]Institut für Neuropathologie, Evangelisches Krankenhaus Bielefeld gGmbH, Bielefeld, Germany
                [45 ]Institut für Neuropathologie, Universitätskinikum Essen, Essen, Germany
                [46 ]Institute of Neuropathology, University Hospital Münster, Münster, Germany
                [47 ]Children’s Cancer Centre, Royal Children’s Hospital; Murdoch Children’s Research Institute; Department of Pediatrics, University of Melbourne; Melbourne, Australia
                [48 ]Institute for Pathology, Katharinenhospital Stuttgart, Stuttgart, Germany
                [49 ]Department of Pathology, Odense University Hospital, Department of Clinical Research, University of Southern Denmark, Odense, Denmark
                [50 ]University College London Cancer Institute and University College London Hospitals, London, United Kingdom.
                [51 ]Department of Pathology, University of Virginia, Charlottesville, Virginia, USA
                [52 ]Institute of Neuropathology, Otto-von-Guericke-University, Magdeburg
                [53 ]Department of Neurosurgery, University Hospital Saarland, Homburg, Saar, Germany
                [54 ]Nicklaus Children’s Hospital Brain Institute, Miami, FL, 33155, USA
                [55 ]Cluster of Excellence, NeuroCure, and Berlin Institute of Health (BIH), Berlin, Germany
                [56 ]Département de Pathologie et Neuropathologie, Hôpital Neurologique, Hospices Civils de Lyon, Lyon, France
                [57 ]Department of Neuropathology, Cork University Hospital, Cork, Ireland
                [58 ]Department of Pathology, Ludwigsburg Hospital, Ludwigsburg, Germany
                [59 ]Department of Neuropathology, Leipzig University, Leipzig, Germany
                [60 ]Department of Cellular Pathology, Queen’s Hospital, Romford, UK
                [61 ]BIOSS Centre for Biological Signalling Studies, University of Freiburg, Germany
                [62 ]Department of Pediatric Oncology and Haematology, Princess Margaret Hospital for Children, GPO Box D184, Perth, Western Australia 6840, Australia
                [63 ]Telethon Kids Institute, University of Western Australia, PO Box 855, Perth, Western Australia 6872, Australia
                [64 ]School of Paediatrics and Child Health, University of Western Australia, GPO Box D184, Perth, Western Australia 6840, Australia
                [65 ]Department of Pediatric Oncology/Hematology, Charité-Universitätsmedizin Berlin, Berlin, Germany
                [66 ]Division of Pediatric Hematology and Oncology, University Medical Center Goettingen, Goettingen, Germany
                [67 ]Department of Pediatrics and Pediatric Hematology / Oncology, Klinikum Oldenburg AöR, Medical Campus University Oldenburg, 26133 Oldenburg, Germany
                [68 ]Department for Pediatric Hematology and Oncology, University Hospital Hamburg-Eppendorf, Hamburg, Germany
                [69 ]Children’s Hospital Augsburg, Swabian Children’s Cancer Centre, Augsburg, Germany
                [70 ]Department of Pediatric Hematology/Oncology, University of Bonn Medical Center, Bonn, Germany
                [71 ]Department of Neuropathology, Insitute of Pathology, Comprehensive Cancer Center (CCC) Mainfranken, University of Würzburg, Würzburg, Germany
                [72 ]Department of Pathology, University of California San Francisco, San Francisco, CA, USA
                [73 ]Division of Molecular Pathology, Institute of Cancer Research, London, UK
                [74 ]Developmental Biology and Cancer Programme, UCL Great Ormond Street Institute of Child Health and Histopathology Department, Great Ormond Street Hospital for Children NHS Foundation Trust, London, UK
                [75 ]Medical Faculty, University of Bonn Medical School, Bonn, Germany
                [76 ]Department of Neurosurgery, University Hospital Carl Gustav Carus, Technische Universität Dresden, Dresden, Germany.
                [77 ]Department of Neurosurgery, University Hospital Hamburg-Eppendorf, Hamburg, Germany.
                [78 ]Department of Neuropathology, Heinrich Heine University Düsseldorf and German Cancer Consortium (DKTK), partner site Essen/Düsseldorf, German Cancer Research Center (DKFZ) Heidelberg, Germany
                [79 ]Department of Pathology, Princess Máxima Center for Pediatric Oncology and University Medical Center Utrecht, Utrecht, the Netherlands, and Department of Pathology, VU University Medical Center, Amsterdam, the Netherlands
                [80 ]Department of Neurology, University Hospital and University of Zurich, Zurich, Switzerland
                [81 ]Department of Pathology, Division of Molecular Histopathology, University of Cambridge, Cambridge, UK.
                [82 ]Department of Neuroradiology, Heidelberg University Hospital, Heidelberg, Germany
                [83 ]Department of Radiation Oncology, Heidelberg University Hospital, Heidelberg, Germany
                [84 ]Department of Pediatrics, Laboratory Medicine and Pathobiology, University of Toronto, Toronto, Ontario, Canada
                [85 ]Division of Hematology/Oncology, McGill University, Montreal, QC, Canada
                [86 ]Department of Developmental Neurobiology, St. Jude Children’s Research Hospital, Memphis, TN, USA
                [87 ]Department of Oncology, St. Jude Children’s Research Hospital, Memphis, TN, USA
                [88 ]Division of Neurosurgery, Arthur and Sonia Labatt Brain Tumor Research Centre, Hospital for Sick Children, University of Toronto, Toronto, Canada
                [89 ]Division of Neuropathology,UCL Hospitlals and Department of Neurodegeneration, Institute of Neurology, University College London, Queen Square, WC1N 3BG, London, UK
                [90 ]Division of Neuropathology, UCL Hospitals and Department of Molecular Neuroscience, Institute of Neurology, University College London, Queen Square, WC1N 3BG, London
                [91 ]NN Burdenko Neurosurgical Institute, Moscow, Russia
                [92 ]Department of Neurology, Universitätsmedizin Mannheim, Medical Faculty Mannheim, Heidelberg University, Mannheim, Germany
                [93 ]Department of Neurology, Heidelberg University Hospital, Heidelberg, Germany
                [94 ]Department of Pediatrics, Memorial Sloan Kettering Cancer Center, New York, NY, USA
                [95 ]NORLUX Neuro-Oncology Laboratory, Luxembourg Institute of Health (LIH); Luxembourg Centre for Systems Biomedicine (LCSB), University of Luxembourg; Laboratoire national de santé (LNS), Dudelange; Luxembourg Centre of Neuropathology (LCNP), all Luxembourg.
                [96 ]Department of Neuropathology, Hannover Medical School (MHH), Hannover, Germany
                [97 ]Department of Pathology, University of Toronto, Toronto, Ontario, Canada
                [98 ]Institute of Neuropathology and Department of Pediatric Hematology and Oncology, University Medical Center, Hamburg-Eppendorf, Germany
                [99 ]Research Institute Children’s Cancer Center, Hamburg, Germany
                [100 ]Section Neuropathology, Institute of Pathology, Sozialstiftung Bamberg, Klinikum am Bruderwald, Bamberg, Germany
                [101 ]Department of Pathology, St. Jude Children’s Research Hospital, Memphis, TN, USA
                [102 ]Division of Neuropathology, Department of Pathology, NYU Langone Medical Center, New York, NY, USA
                Author notes
                [+]

                current address: Department of Pathology and Center for Cancer Research, Massachusetts General Hospital and Harvard Medical School, Boston, MA, USA, and Broad Institute of MIT and Harvard, Cambridge, MA, USA

                [#]

                These authors jointly directed this work

                Correspondence should be addressed to S.M.P. ( s.pfister@ 123456dkfz.de ) or A.v.D. ( Andreas.vonDeimling@ 123456med.uni-heidelberg.de )
                Article
                NIHMS942946
                10.1038/nature26000
                6093218
                29539639
                1aa6b405-2321-4253-8513-c98c2a9aea1a

                Users may view, print, copy, and download text and data-mine the content in such documents, for the purposes of academic research, subject always to the full Conditions of use: http://www.nature.com/authors/editorial_policies/license.html#terms

                Reprints and permissions information is available at www.nature.com/reprints. S.M.P, A.v.D, D.T.W.J., D.C., V.Hovestadt, M.Sill, M.Bewerunge-Hudler and M.Schick declare competing financial interests: A patent on a “DNA-methylation based method for classifying tumor species of the brain” has been applied for by the Deutsches Krebsforschungszentrum Stiftung des öffentlichen Rechts and Ruprecht-Karls-Universität Heidelberg (EP 3067432 A1). The other authors declare no competing financial interest. Correspondence and request for materials should be addressed to S.M.P. ( s.pfister@ 123456dkfz.de ) or A.v.D. ( Andreas.vonDeimling@ 123456med.uni-heidelberg.de ).

                History
                Categories
                Article

                Uncategorized
                Uncategorized

                Comments

                Comment on this article