Back

Distinct geometrical landscapes distinguish between modes of tristability in gene regulatory networks

Duddu, A. S.; Jolly, M. K.; Raju, A.

2025-10-13 systems biology
10.1101/2025.10.11.681792 bioRxiv
Show abstract

Geometrical models have been recently used to construct landscapes for cell-fate decisions, inferred directly from experimental data. However, such quantitative cell-fate data is available for a few systems only; instead, gene regulatory networks dynamics have been studied for a broader set of biological decision-making scenarios. Thus, connecting the geometry of cell-fate decisions to their underlying regulatory networks remains an open question. Recently, two regulatory networks have been shown to exhibit tristability - a toggle switch with self-activation, and a toggle triad. Here, we show that these two motifs are distinct from a geometrical point of view, and identify two bifurcations in their behaviour: the standard cusp and the elliptic umbillic. We study experimentally accessible signatures of the differences in tristability between the two motifs. We also show how the standard cusp can be used to quantitatively model cell fate transition data for the Epithelial to Mesenchymal transition on TGF-{beta} induction in the context of cancer cells. Our work uncovers geometrical signatures of gene regulatory motifs and demonstrates how different gene regulatory networks can encode tristability in dynamically distinct ways.

Published in Journal of the Royal Society Interface · not in our set (fewer than 10 published preprints to learn from) · training set

Matching journals

The top 6 journals account for 50% of the predicted probability mass.

50% of probability mass above

"Similar papers" are the closest papers from that journal in the model's embedding space. They show what the match is built on, but the ranking comes mostly from a classifier over the whole training set, not from these examples alone.