Gene regulation is a dynamic process that underlies all aspects of human development, disease response, and other key biological processes. The reconstruction of temporal gene regulatory networks has conventionally relied on regression analysis, graphical models, or other types of relevance networks. With the large increase in time series single-cell data, new approaches are needed to address the unique scale and nature of this data for reconstructing such networks. Here, we develop a deep neural network, Marlene, to infer dynamic graphs from time series single-cell gene expression data. Marlene constructs directed gene networks using a self-attention mechanism where the weights evolve over time using recurrent units. By employing meta learning, the model is able to recover accurate temporal networks even for rare cell types. In addition, Marlene can identify gene interactions relevant to specific biological responses, including COVID-19 immune response, fibrosis, and aging. Biological systems are dynamic, changing over time in response to various stimuli and events. To construct accurate models of biological activity during development, disease progression, treatment response, and other biological processes, it is essential to track their evolution over time (Bar-Joseph et al., 2012). Studying the regulation of these dynamic processes is key for understanding the underlying mechanisms that drive the response and for identifying potential interventions that can serve as cures for diseases (Silverman et al., 2020). Much of the research in this area is focused on the reconstruction of regulatory networks (Karlebach & Shamir, 2008; Badia-I-Mompel et al., 2023).

This article contains spoilers for The Last of Us Episode 9, "Look for the Light." The Last of Us has been roundly praised as the best video-game adaptation ever made, even the first to be truly great, and part of that greatness is that you don't need to have played the original games to appreciate it. Although the HBO series is replete with moments from the games repeated beat for beat and even shot for shot, it's not hobbled by mindless fidelity to its source, and it finds ways to exploit its new medium that would never work if you were sitting in front of the TV with a PlayStation controller instead of a remote control. But in the final episode of the first season, "Look for the Light," The Last of Us returns to its source material in a way that comes close to wrecking everything the show has accomplished. Joel and Ellie have finally reached the goal they've been headed toward the entire season: the Firefly encampment in Salt Lake City. Joel has spent the past 20 years grieving the murder of his teenage daughter, Sarah, at the beginning of the Cordyceps pandemic, and the more recent death of his partner, Tess, and an uneasy reunion with his brother has underlined the lesson that it's best for him not to care for anyone at all.

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While there are some who scoff at the suggestion of a "curse" on live-action video game adaptations, the creators of The Last of Us are not among them. They believed in the curse; they feared a TV show. A flop would tarnish the game's legacy. Few would have had a better claim to this skepticism than Merle Dandridge, Troy Baker, and Ashley Johnson, who played Marlene, Joel, and Ellie, respectively, in the games. Back then, decked out in black mocap suits, pandemic-ravaged America existed only in their imagination.