Cellular proliferation biases clonal lineage tracing and trajectory inference

Abstract

We identify a fundamental statistical phenomenon in single-cell time courses with clone-based lineage tracing. Through simple probabilistic arguments, we show how the relative growth rates of cells influence the probability that they will be sampled in clones observed across multiple time points. We support these arguments with a simple simulation study and a time-course of T-cell development, and we demonstrate that this bias can impact fate probability predictions from trajectory inference methods. Finally, we explore how to develop trajectory inference methods which are robust to this bias. In particular, we show how to extend LineageOT [1] to use data from clones observed across multiple time points.