Knowledge bases and software support for variant interpretation in precision oncology.

Journal: Briefings in bioinformatics
Published Date: Nov 5, 2021

Abstract

Precision oncology is a rapidly evolving interdisciplinary medical specialty. Comprehensive cancer panels are becoming increasingly available at pathology departments worldwide, creating the urgent need for scalable cancer variant annotation and molecularly informed treatment recommendations. A wealth of mainly academia-driven knowledge bases calls for software tools supporting the multi-step diagnostic process. We derive a comprehensive list of knowledge bases relevant for variant interpretation by a review of existing literature followed by a survey among medical experts from university hospitals in Germany. In addition, we review cancer variant interpretation tools, which integrate multiple knowledge bases. We categorize the knowledge bases along the diagnostic process in precision oncology and analyze programmatic access options as well as the integration of knowledge bases into software tools. The most commonly used knowledge bases provide good programmatic access options and have been integrated into a range of software tools. For the wider set of knowledge bases, access options vary across different parts of the diagnostic process. Programmatic access is limited for information regarding clinical classifications of variants and for therapy recommendations. The main issue for databases used for biological classification of pathogenic variants and pathway context information is the lack of standardized interfaces. There is no single cancer variant interpretation tool that integrates all identified knowledge bases. Specialized tools are available and need to be further developed for different steps in the diagnostic process.

Authors

  • Florian Borchert
    Digital Health Center, Hasso Plattner Institute, University of Potsdam, Germany.
  • Andreas Mock
    Department of Translational Medical Oncology (TMO), National Center for Tumor Diseases (NCT) Heidelberg, German Cancer Research Center (DKFZ) Heidelberg, Im Neuenheimer Feld 460, 69120 Heidelberg, Germany.
  • Aurelie Tomczak
    Stanford Institute for Immunity, Transplantation and Infection (ITI), Stanford University, Stanford, CA, 94305, USA.
  • Jonas Hügel
    Department of Medical Informatics, University Medical Center Göttingen, Von-Siebold-Str. 3, 37099 Göttingen, Germany.
  • Samer Alkarkoukly
    CECAD, Faculty of Medicine and University Hospital Cologne, University of Cologne, Joseph-Stelzmann-Straße 26, 50931 Cologne.
  • Alexander Knurr
    Division of Medical Informatics for Translational Oncology, German Cancer Research Center (DKFZ) Heidelberg, Im Neuenheimer Feld 280, 69120 Heidelberg, Germany.
  • Anna-Lena Volckmar
    Institute of Pathology Heidelberg, Heidelberg University Hospital, Im Neuenheimer Feld 224, 69120 Heidelberg, Germany.
  • Albrecht Stenzinger
    From the Division of Radiology, German Cancer Research Center (DKFZ), Im Neuenheimer Feld 280, 69120 Heidelberg, Germany (P.S., J.P.R., P.K., H.P.S., D.B.); Medical Image Computing, German Cancer Research Center (DKFZ), Heidelberg, Germany (S.K., K.H.M.H.); Department of Urology, University of Heidelberg Medical Center, Heidelberg, Germany (J.P.R., M.H.); Division of Biostatistics, German Cancer Research Center (DKFZ), Heidelberg, Germany (M.W.); Department of Neuroradiology, University of Heidelberg Medical Center, Heidelberg, Germany (P.K.); Junior Group Medical Imaging and Radiology-Cancer Prevention, German Cancer Research Center (DKFZ), Heidelberg, Germany (S.B.); Division of Medical Physics, German Cancer Research Center (DKFZ), Heidelberg, Germany (T.A.K.); Institute of Pathology, University of Heidelberg Medical Center, Heidelberg, Germany (A.S.); and German Cancer Consortium (DKTK), Heidelberg, Germany (H.P.S., K.H.M.H., D.B.).
  • Peter Schirmacher
    Institute of Pathology, University Hospital Heidelberg, Heidelberg, Germany; Liver Cancer Center Heidelberg, University Hospital Heidelberg, Heidelberg, Germany.
  • Jürgen Debus
    Department of Radiation Oncology, Heidelberg University Hospital, Heidelberg, Germany; Heidelberg Institute of Radiation Oncology, Heidelberg, Germany; Heidelberg Ion-Beam Therapy Center, Heidelberg, Germany.
  • Dirk Jäger
    Department of Medical Oncology and Internal Medicine VI, National Center for Tumor Diseases, University Hospital Heidelberg, Heidelberg, Germany.
  • Thomas Longerich
    Institute of Pathology Heidelberg, Heidelberg University Hospital, Im Neuenheimer Feld 224, 69120 Heidelberg, Germany.
  • Stefan Fröhling
    National Center for Tumor Diseases (NCT), German Cancer Research Center (DKFZ), Im Neuenheimer Feld 460, 69120 Heidelberg, Germany.
  • Roland Eils
    Center for Digital Health, Berlin Institute of Health, Charité - University Medicine Berlin, Berlin, Germany. roland_eils@fudan.edu.cn.
  • Nina Bougatf
    Department of Radiation Oncology, Heidelberg University Hospital, Im Neuenheimer Feld 400, 69120 Heidelberg, Germany.
  • Ulrich Sax
    Department of Medical Informatics, University Medical Center Goettingen, Goettingen, Germany.
  • Matthieu-P Schapranow
    Digital Health Center, Hasso Plattner Institute, University of Potsdam, Germany.

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