No abstract

The recent breakthrough of single-cell RNA velocity methods brings attractive promises to reveal directed trajectory on cell differentiation, states transition and response to perturbations. However, the existing RNA velocity methods are often found to return erroneous results, partly due to model violation or lack of temporal regularization. Here, we present UniTVelo, a statistical framework of RNA velocity that models the dynamics of spliced and unspliced RNAs via flexible transcription activities. Uniquely, it also supports the inference of a unified latent time across the transcriptome. With ten datasets, we demonstrate that UniTVelo returns the expected trajectory in different biological systems, including hematopoietic differentiation and those even with weak kinetics or complex branches.

RNA velocity is a promising technique for quantifying cellular transitions from single-cell transcriptome experiments and revealing transient cellular dynamics among a heterogeneous cell population. However, the cell transitions estimated from high-dimensional RNA velocity are often unstable or inaccurate, partly due to the high technical noise and less informative projection. Here, we present Velocity Autoencoder (VeloAE), a tailored representation learning method, to learn a low-dimensional representation of RNA velocity on which cellular transitions can be robustly estimated. On various experimental datasets, we show that VeloAE can both accurately identify stimulation dynamics in time-series designs and effectively capture expected cellular differentiation in different biological systems. VeloAE, therefore, enhances the usefulness of RNA velocity for studying a wide range of biological processes.

Although massive open online courses (MOOCs) have attracted much worldwide attention, scholars still understand little about the specific elements that students find engaging in these large open courses. This study offers a new original contribution by using a machine learning classifier to analyze 24,612 reflective sentences posted by 5,884 students, who participated in one or more of 18 highly rated MOOCs. Highly rated MOOCs were sampled because they exemplify good practices or teaching strategies. We selected highly rated MOOCs from Coursetalk, an open user-driven aggregator and discovery website that allows students to search and review various MOOCs. We defined a highly rated MOOC as a free online course that received an overall five-star course quality rating, and received at least 50 reviews from different learners within a specific subject area. We described six specific themes found across the entire data corpus: (a) structure and pace, (b) video, (c) instructor, (d) content and resources, (e) interaction and support, and (f) assignment and assessment. The findings of this study provide valuable insight into factors that students find engaging in large-scale open online courses.