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Detektion und Interpretation somatischer Varianten in der Molekularpathologie

Detection and interpretation of somatic variants in molecular pathology

  • Schwerpunkt: Präzisionsonkologie
  • Published:
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Zusammenfassung

Hintergrund

Die Datenauswertung ist aufgrund zunehmender Datenmengen und Informationsquellen ein kritischer Schritt bei der Parallelsequenzierung.

Fragestellung

Darstellung der Fallstricke bei der Auswertung der Variantenlisten, die bei der Parallelsequenzierung generiert werden, Empfehlungen zu Softwareanwendungen und Datenbanken.

Material und Methoden

Aufzeigen der angewandten Filterschritte und Auswertekriterien und -vorschriften anhand von Beispielen aus dem Arbeitsalltag, vergleichende Analyse vorhandener Datenbanken somatischer Varianten, Beschreibung des Aufbaus einer individualisierten Datenbank.

Ergebnisse

Das Filtern der Varianten ist ein mehrstufiger Prozess, bei dem Informationen aus verschiedenen Datenbanken einfließen können. Die Plausibilität des „variant callings“ sollte im Integrative Genomics Viewer überprüft und die Varianten anschließend nach den Vorschriften der Human Genome Variation Society (HGVS) benannt werden. Zur Interpretation der Varianten können verschiedene Datenbanken herangezogen werden, die jeweils Vor- und Nachteile zeigen. Eine individualisierte Datenbank kann mit der Open-source-Anwendung cBioPortal aufgebaut werden.

Schlussfolgerung

Es können verschiedene Anwendungen und Datenbanken zur Analyse von Daten der Parallelsequenzierung genutzt werden. Der Einsatz ist u. a. von lokalen Gegebenheiten abhängig. Vor dem Einsatz sollten alle Arbeitsabläufe einer extensiven Validierung unterzogen werden.

Abstract

Background

Due to the increasing amount of data and sources of information, data evaluation is a crucial step in parallel sequencing.

Objectives

Illustration of pitfalls in evaluating the variant list of parallel sequencing and recommendations regarding software tools and databases.

Methods

Description of filtering steps used, demonstration of criteria and recommendations for annotation by examples from everyday work, comparative analysis of databases with somatic variants, description of the installation of an individualized database.

Results

Variant filtering is a multistep process using information from different databases. The plausibility of variant calling should be verified using the Integrative Genomics Viewer and variants should be described according to the Human Genome Variation Society (HGVS) recommendations. Different databases, which all show advantages and disadvantages, are available for variant interpretation. An individualized database can be built up with the open-source tool cBioPortal.

Conclusions

Different tools and databases might be used for the analysis of parallel sequencing data. The application depends on, amongst other things, the local situation and has to be extensively validated.

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Authors and Affiliations

  1. Institut für Pathologie, Universitätsklinikum Köln, Kerpener Str. 62, Gebäude 8e, 50937, Köln, Deutschland

    S. Merkelbach-Bruse, J. Rehker & J. Siemanowski

  2. Institut für Pathologie, Charité Universitätsmedizin Berlin, Berlin, Deutschland

    F. Klauschen

  3. Standort Berlin, Deutsches Konsortium für Translationale Krebsforschung (DKTK), Berlin, Deutschland

    F. Klauschen

  4. Deutsches Krebsforschungszentrum (DKFZ), Heidelberg, Deutschland

    F. Klauschen

Authors
  1. S. Merkelbach-Bruse
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  2. J. Rehker
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  3. J. Siemanowski
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  4. F. Klauschen
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Corresponding author

Correspondence to S. Merkelbach-Bruse.

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Interessenkonflikt

S. Merkelbach-Bruse, J. Rehker, J. Siemanowski und F. Klauschen geben an, dass kein Interessenkonflikt besteht.

Für diesen Beitrag wurden von den Autoren keine Studien an Menschen oder Tieren durchgeführt. Für die aufgeführten Studien gelten die jeweils dort angegebenen ethischen Richtlinien.

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Schwerpunktherausgeber

K. W. Schmid, Essen

H. A. Baba, Essen

H.-U. Schildhaus, Essen

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Merkelbach-Bruse, S., Rehker, J., Siemanowski, J. et al. Detektion und Interpretation somatischer Varianten in der Molekularpathologie. Pathologe 40, 243–249 (2019). https://doi.org/10.1007/s00292-019-0603-6

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