The liver performs over 500 metabolic functions , resulting in synthesis of products that are released into the blood stream (e.g. glucose derived from glycogenesis, plasma proteins/polypetides, clotting factors and urea), or that are excreted to the intestinal tract (bile). 

Earlier liver zonation studies relied on a three-zone model (periportal, mid-lobular, pericentral) or discretized the portal-to-central axis into twenty bins, Well-studied metabolic and signaling gradients occur over a relatively short physical distance of approximately 20 hepatocytes or about 385 μm in humans*. New models capture the gradual nature of biological processes in the lobule without artificial boundaries**. New approach models protein expression as continuous trajectories through space using linear mixed models, which account for patient-specific variations while avoiding the need to bin the spatial trajectory and reducing sensitivity to missing values, e.g. due to dropout samples.

* Takahashi, T. Lobular Structure of the Human Liver from the Viewpoint of Hepatic Vascular Architecture. Tohoku J. Exp. Med. 101, 119–140 (1970).

** Cunningham, R. P. & Porat-Shliom, N. Liver Zonation – Revisiting Old Questions With New Technologies. Front. Physiol. 12, (2021); Rosenberger, F. A. et al. Spatial single-cell mass spectrometry defines zonation of the hepatocyte proteome. Nat. Methods 20, 1530–1536 (2023).