Reconstructing Clonal Evolution—A Systematic Evaluation of Current Bioinformatics Approaches

Sarah Sandmann (), Silja Richter, Xiaoyi Jiang and Julian Varghese
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Sarah Sandmann: Institute of Medical Informatics, University of Münster, 48149 Münster, Germany
Silja Richter: Institute of Medical Informatics, University of Münster, 48149 Münster, Germany
Xiaoyi Jiang: Department of Computer Science, University of Münster, 48149 Münster, Germany
Julian Varghese: Institute of Medical Informatics, University of Münster, 48149 Münster, Germany

IJERPH, 2023, vol. 20, issue 6, 1-27

Abstract: The accurate reconstruction of clonal evolution, including the identification of newly developing, highly aggressive subclones, is essential for the application of precision medicine in cancer treatment. Reconstruction, aiming for correct variant clustering and clonal evolution tree reconstruction, is commonly performed by tedious manual work. While there is a plethora of tools to automatically generate reconstruction, their reliability, especially reasons for unreliability, are not systematically assessed. We developed clevRsim—an approach to simulate clonal evolution data, including single-nucleotide variants as well as (overlapping) copy number variants. From this, we generated 88 data sets and performed a systematic evaluation of the tools for the reconstruction of clonal evolution. The results indicate a major negative influence of a high number of clones on both clustering and tree reconstruction. Low coverage as well as an extreme number of time points usually leads to poor clustering results. An underlying branched independent evolution hampers correct tree reconstruction. A further major decline in performance could be observed for large deletions and duplications overlapping single-nucleotide variants. In summary, to explore the full potential of reconstructing clonal evolution, improved algorithms that can properly handle the identified limitations are greatly needed.

Keywords: clonal evolution; single-nucleotide variant; copy number variant; simulation (search for similar items in EconPapers)
JEL-codes: I I1 I3 Q Q5 (search for similar items in EconPapers)
Date: 2023
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