TY - JOUR T1 - Transcriptomic entropy quantifies cardiomyocyte maturation at single cell level JF - bioRxiv DO - 10.1101/2020.04.02.022632 SP - 2020.04.02.022632 AU - Suraj Kannan AU - Michael Farid AU - Brian L. Lin AU - Matthew Miyamoto AU - Chulan Kwon Y1 - 2020/01/01 UR - http://biorxiv.org/content/early/2020/04/03/2020.04.02.022632.abstract N2 - While pluripotent stem cell-derived cardiomyocytes (PSC-CMs) offer tremendous potential for a range of clinical applications, their use has been constrained by the failure to mature these cells to a fully adult-like phenotype. Extensive efforts are currently underway with the goal to mature PSC-CMs. However, comprehensive metrics to benchmark the maturation status and trajectory of PSC-CMs have not been established. Here, we developed a novel approach to quantify CM maturation through single cell transcriptomic entropy. We found that transcriptomic entropy is robust across datasets regardless of differences in isolation protocols, library preparation methods, and other potential batch effects. We analyzed over 40 single cell RNA-sequencing (scRNA-seq) datasets and over 45,000 CMs to establish a cross-study, cross-species reference of CM maturation based on transcriptomic entropy. We subsequently computed the maturation status of PSC-CMs by direct comparison to in vivo development. Our study presents a robust, interpretable, and easy-to-use metric for quantifying CM maturation.Significance Statement There is significant interest in generating mature cardiomyocytes from pluripotent stem cells. However, there are currently few effective metrics to quantify the maturation status of a single cardiomyocyte. We developed a new metric for measuring cardiomyocyte maturation using single cell RNA-sequencing data. This metric, called entropy score, uses the gene distribution to estimate maturation at the single cell level. Entropy score enables comparing pluripotent stem cell-derived cardiomyocytes directly against endogenously-isolated cardiomyocytes. Thus, entropy score can better assist in development of approaches to improve the maturation of pluripotent stem cell-derived cardiomyocytes. ER -