A multiresolution framework to characterize single-cell state landscapes

Shahin Mohammadi, Jose Davila-Velderrain and Manolis Kellis

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Oct 18, 2019
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Received Date: 24th September 19

Dissecting the cellular heterogeneity embedded in single-cell transcriptomic data is challenging. Although a large number of methods and approaches exist, robustly identifying underlying cell states and their associations is still a major challenge; given the nonexclusive and dynamic influence of multiple unknown sources of variability, the existence of state continuum at the time-scale of observation, and the inevitable snapshot nature of experiments. As a way to address some of these challenges, here we introduce ACTIONet, a comprehensive framework that combines archetypal analysis and network theory to provide a ready-to-use analytical approach for multiresolution single-cell state characterization. ACTIONet uses multilevel matrix decomposition and network reconstruction to simultaneously learn cell state patterns, quantify single-cell states, and reconstruct a reproducible structural representation of the transcriptional state space that is geometrically mapped to a color space. A color-enhanced quantitative view of cell states enables novel visualization, prediction, and annotation approaches. Using data from multiple tissues, organisms, and developmental conditions, we illustrate how ACTIONet facilitates the reconstruction and exploration of single-cell state landscapes.

Read in full at bioRxiv.

This is an abstract of a preprint hosted on an independent third party site. It has not been peer reviewed but is currently under consideration at Nature Communications.

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