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We introduce a  k -mer-based computational protocol, DE-kupl, for capturing local RNA variation in a set of RNA-seq libraries, independently of a reference genome or transcriptome. DE-kupl extracts all  k -mers with differential abundance directly from the raw data files. This enables the retrieval of virtually all variation present in an RNA-seq data set. This variation is subsequently assigned to biological events or entities such as differential long non-coding RNAs, splice and polyadenylation variants, introns, repeats, editing or mutation events, and exogenous RNA. Applying DE-kupl to human RNA-seq data sets identified multiple types of novel events, reproducibly across independent RNA-seq experiments.   Electronic supplementary material  The online version of this article (doi:10.1186/s13059-017-1372-2) contains supplementary material, which is available to authorized users.

DE-kupl: exhaustive capture of biological variation in RNA-seq data through k-mer decomposition