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Reference-free transcriptome signatures for prostate cancer prognosis

Abstract : Background. RNA-seq data are increasingly used to derive prognostic signatures for cancer outcome prediction. A limitation of current predictors is their reliance on reference gene annotations, which amounts to ignoring large numbers of non-canonical RNAs produced in disease tissues. A recently introduced kind of transcriptome classifier operates entirely in a reference-free manner, relying on k-mers extracted from patient RNA-seq data. Methods. In this paper, we set out to compare conventional and reference-free signatures in risk and relapse prediction of prostate cancer. To compare the two approaches as fairly as possible, we set up a common procedure that takes as input either a k-mer count matrix or a gene expression matrix, extracts a signature and evaluates this signature in an independent dataset. Results. We find that both gene-based and k-mer based classifiers had similarly high performances for risk prediction and a markedly lower performance for relapse prediction. Interestingly, the reference-free signatures included a set of sequences mapping to novel lncRNAs or variable regions of cancer driver genes that were not part of gene-based signatures. Conclusions. Reference-free classifiers are thus a promising strategy for the identification of novel prognostic RNA biomarkers.
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Submitted on : Friday, September 25, 2020 - 10:06:54 AM
Last modification on : Tuesday, October 19, 2021 - 4:10:23 PM
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Ha Nguyen, Haoliang Xue, Virginie Firlej, Yann Ponty, Mélina Gallopin, et al.. Reference-free transcriptome signatures for prostate cancer prognosis. BMC Cancer, BioMed Central, 2021, 21 (394), ⟨10.1186/s12885-021-08021-1⟩. ⟨hal-02948844⟩



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