PaperPlayer biorxiv bioinformatics

Multi-resolution characterization of molecular taxonomies in bulk and single-cell transcriptomics data


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Link to bioRxiv paper:
http://biorxiv.org/cgi/content/short/2020.11.05.370197v1?rss=1
Authors: Reed, E. R., Monti, S.
Abstract:
As high-throughput genomics assays become more efficient and cost effective, their utilization has become standard in large-scale biomedical projects. These studies are often explorative, in that relationships between samples are not explicitly defined a priori, but rather emerge from data-driven discovery and annotation of molecular subtypes, thereby informing hypotheses and independent evaluation. Here, we present K2Taxonomer, a novel unsupervised recursive partitioning algorithm and associated R package that utilize ensemble learning to identify robust subgroups in a "taxonomy-like" structure (https://github.com/montilab/K2Taxonomer). K2Taxonomer was devised to accommodate different data paradigms, and is suitable for the analysis of both bulk and single-cell transcriptomics data. For each of these data types, we demonstrate the power of K2Taxonomer to discover known relationships in both simulated and human tissue data. We conclude with a practical application on breast cancer tumor infiltrating lymphocyte (TIL) single-cell profiles, in which we identified co-expression of translational machinery genes as a dominant transcriptional program shared by T cells subtypes, associated with better prognosis in breast cancer tissue bulk expression data.
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