Unraveling dynamically encoded latent transcriptomic patterns in pancreatic cancer cells by topic modeling.

Building a comprehensive topic model has become an important research tool in single-cell genomics. With a topic model, we can decompose and ascertain distinctive cell topics shared across multiple cells, and the gene programs implicated by each topic can later serve as a predictive model in translational studies. Here, we present a Bayesian topic model that can uncover short-term RNA velocity patterns from a plethora of spliced and unspliced single-cell RNA-sequencing (RNA-seq) counts. We showed that modeling both types of RNA counts can improve robustness in statistical estimation and can reveal new aspects of dynamic changes that can be missed in static analysis. We showcase that our modeling framework can be used to identify statistically significant dynamic gene programs in pancreatic cancer data. Our results discovered that seven dynamic gene programs (topics) are highly correlated with cancer prognosis and generally enrich immune cell types and pathways.

Applying Machine Learning to Stem Cell Culture and Differentiation.

Machine learning techniques are increasingly becoming incorporated into biological research workflows in a variety of disciplines, most notably cancer research and drug discovery. Efforts in stem cell research comparatively lag behind. We detail key paradigms in machine learning, with a focus on equipping stem cell biologists with the understanding necessary to begin conceptualizing and designing machine learning workflows within their own domain of expertise. Supervised approaches in both regression and classification as well as unsupervised clustering techniques are all covered, with examples from across the biological sciences. High-throughput, high-content, multiplex assays for data acquisition are also discussed in the form of single-cell RNA sequencing and image-based approaches. Lastly, potential applications in stem cell biology, including the development of novel cell types, and improving model maturation are also discussed. Machine learning approaches applied in stem cell biology show promise in accelerating progress in developmental biology, drug screening, disease modeling, and personalized medicine. © 2021 Wiley Periodicals LLC.