PuSH - Publikationsserver des Helmholtz Zentrums München

Bredthauer, C. ; Fischer, A.* ; Ahari, A.J.* ; Cao, X.* ; Weber, J.* ; Rad, L.* ; Rad, R.* ; Wachutka, L.* ; Gagneur, J.

Transmicron: Accurate prediction of insertion probabilities improves detection of cancer driver genes from transposon mutagenesis screens.

Nucleic Acids Res. 51:e21 (2023)
DOI PMC
Creative Commons Lizenzvertrag
Open Access Gold möglich sobald Verlagsversion bei der ZB eingereicht worden ist.
Transposon screens are powerful in vivo assays used to identify loci driving carcinogenesis. These loci are identified as Common Insertion Sites (CISs), i.e. regions with more transposon insertions than expected by chance. However, the identification of CISs is affected by biases in the insertion behaviour of transposon systems. Here, we introduce Transmicron, a novel method that differs from previous methods by (i) modelling neutral insertion rates based on chromatin accessibility, transcriptional activity and sequence context and (ii) estimating oncogenic selection for each genomic region using Poisson regression to model insertion counts while controlling for neutral insertion rates. To assess the benefits of our approach, we generated a dataset applying two different transposon systems under comparable conditions. Benchmarking for enrichment of known cancer genes showed improved performance of Transmicron against state-of-the-art methods. Modelling neutral insertion rates allowed for better control of false positives and stronger agreement of the results between transposon systems. Moreover, using Poisson regression to consider intra-sample and inter-sample information proved beneficial in small and moderately-sized datasets. Transmicron is open-source and freely available. Overall, this study contributes to the understanding of transposon biology and introduces a novel approach to use this knowledge for discovering cancer driver genes.
Altmetric
Weitere Metriken?
[➜Einloggen]
Zusatzinfos bearbeiten [➜Einloggen]
Publikationstyp Artikel: Journalartikel
Dokumenttyp Wissenschaftlicher Artikel
Korrespondenzautor
Schlagwörter Sleeping-beauty; Piggybac Transposon; Site Preferences; Discovery; Genome; Integration; Chromatin; Selection; Reintegration; Resolution
ISSN (print) / ISBN 0305-1048
e-ISSN 1362-4962
Zeitschrift Nucleic Acids Research
Quellenangaben Band: 51, Heft: 4, Seiten: , Artikelnummer: e21 Supplement: ,
Verlag Oxford University Press
Verlagsort Great Clarendon St, Oxford Ox2 6dp, England
Nichtpatentliteratur Publikationen
Begutachtungsstatus Peer reviewed
Institut(e) Institute of Computational Biology (ICB)
Förderungen Bundesministerium fur Bildung und Forschung
Deutsche Krebshilfe
Deutsche Forschungsgemeinschaft (DFG)
German Bundesministerium fur Bildung und Forschung (BMBF) through the VALE (Entdeckung und Vorhersage der Wirkung von genetischen Varianten durch Artifizielle Intelligenz fur LEukamie Diagnose und Subtyp-Identifizierung) project