Random walk informed heterogeneity detection reveals how the lymph node conduit network influences T cells collective exploration behavior

Abstract

Random walks on networks are widely used to model stochastic processes such as search strategies, transportation problems or disease propagation. A prominent example of such process is the dynamics of naive T cells within the lymph node while they are scanning for antigens. The observed T cells trajectories in small sub-volumes of the lymph node are well modeled as a random walk and they have been shown to follow the lymphatic conduit network as substrate for migration. One can then ask how does the connectivity patterns of the lymph node conduit network affect the T cells collective exploration behavior. In particular, does the network display properties that are uniform across the whole volume of the lymph node or can we distinguish some heterogeneities? We propose a workflow to accurately and efficiently define and compute these quantities on large networks, which enables us to characterize heterogeneities within a very large published dataset of Lymph Node Conduit Network. To establish the significance of our results, we compared the results obtained on the lymph node to null models of varying complexity. We identified significantly heterogeneous regions characterized as “remote regions” at the poles and next to the medulla, while a large portion of the network promotes uniform exploration by T cells.