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SEquence Evaluation throughk-mer Representation (SEEKR) is a method of sequence comparison that uses sequence substrings calledk-mers to quantify the nonlinear similarity between nucleic acid species. We describe the development of new functions within SEEKR that enable end-users to estimateP-values that ascribe statistical significance to SEEKR-derived similarities, as well as visualize different aspects ofk-mer similarity. We apply the new functions to identify chromatin-enriched lncRNAs that containXIST-like sequence features, and we demonstrate the utility of applying SEEKR on lncRNA fragments to identify potential RNA-protein interaction domains. We also highlight ways in which SEEKR can be applied to augment studies of lncRNA conservation, and we outline the best practice of visualizing RNA-seq read density to evaluate support for lncRNA annotations before their in-depth study in cell types of interest.more » « less
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