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Live-cell microscopy routinely provides massive amounts of time-lapse images of complex cellular systems under various physiological or therapeutic conditions. However, this wealth of data remains difficult to interpret in terms of causal effects. Here, we describe CausalXtract, a flexible computational pipeline that discovers causal and possibly time-lagged effects from morphodynamic features and cell–cell interactions in live-cell imaging data. CausalXtract methodology combines network-based and information-based frameworks, which is shown to discover causal effects overlooked by classical Granger and Schreiber causality approaches. We showcase the use of CausalXtract to uncover novel causal effects in a tumor-on-chip cellular ecosystem under therapeutically relevant conditions. In particular, we find that cancer-associated fibroblasts directly inhibit cancer cell apoptosis, independently from anticancer treatment. CausalXtract uncovers also multiple antagonistic effects at different time delays. Hence, CausalXtract provides a unique computational tool to interpret live-cell imaging data for a range of fundamental and translational research applications.

Summary: Discovering causal effects is at the core of scientific investigation but remains challenging when only observational data are available. In practice, causal networks are difficult to learn and interpret, and limited to relatively small datasets. We report a more reliable and scalable causal discovery method (iMIIC), based on a general mutual information supremum principle, which greatly improves the precision of inferred causal relations while distinguishing genuine causes from putative and latent causal effects. We showcase iMIIC on synthetic and real-world healthcare data from 396,179 breast cancer patients from the US Surveillance, Epidemiology, and End Results program. More than 90% of predicted causal effects appear correct, while the remaining unexpected direct and indirect causal effects can be interpreted in terms of diagnostic procedures, therapeutic timing, patient preference or socio-economic disparity. iMIIC’s unique capabilities open up new avenues to discover reliable and interpretable causal networks across a range of research fields.

In this paper, we present an agent-based model for studying the impact of ‘myside bias’ on the argumentative dynamics in scientific communities. Recent insights in cognitive science suggest that scientific reasoning is influenced by ‘myside bias’. This bias manifests as a tendency to prioritize the search and generation of arguments that support one’s views rather than arguments that undermine them. Additionally, individuals tend to apply more critical scrutiny to opposing stances than to their own. Although myside bias may pull individual scientists away from the truth, its effects on communities of reasoners remain unclear. The aim of our model is two-fold: first, to study the argumentative dynamics generated by myside bias, and second, to explore which mechanisms may act as a mitigating factor against its pernicious effects. Our results indicate that biased communities are epistemically less successful than non-biased ones, and that they also tend to be less polarized than non-biased ones. Moreover, we find that two socio-epistemic mechanisms help communities to mitigate the effect of the bias: the presence of a common filter on weak arguments, which can be interpreted as shared beliefs, and an equal distribution of agents for each alternative at the start of the scientific debate. [ABSTRACT FROM AUTHOR]