We’ve got an thrilling new bioRxiv story that simply went dwell! This one takes a computational immunology strategy to understanding tissue-resident lymphocytes. The story highlights the additional worth mathematical modelling can deliver to biology.
It begins with a big multi-tissue multi-timepoint parabiosis experiment we ran to grasp tissue Tregs. Václav Gergelits, lead writer on the examine, noticed larger potential on this dataset to grasp the kinetics of lymphocyte migration broadly.
We extracted turnover information for CD4, CD8, Treg, B cells and NK cells from 17 tissue sources, and generated a classy mannequin of migration, activation and demise for every lineage and tissue. The Markov chain modelling discovered high-confidence options that matched the empirical information superbly.
This tells us a probabilistic mannequin and three distinct states (resting/activated/resident) are ample to recapitulate the advanced migratory and tissue-residency behaviour of those cells. The cell states change chances, however the behaviour remains to be *probabilistic*.
This implies lymphocytes do not have a residency “clock”. We will measure the typical dwell occasions for resident cells, but when this common residency time is 3 weeks, it doesn’t imply cells have a 3-week timer. It means the cells have a day by day likelihood of leaving that provides a 3 week common. The cube roll comes up earlier for some cells than for others, inside these cells being intrinsically totally different. Like radioactive decay of atoms, it’s simply likelihood – there’s nothing intrinsically totally different concerning the uranium atoms that decay after per week vs people who decay after one million years, they simply had totally different rolls of the cube.
This strategy can clarify a lot of the variation in cell destiny while not having to invoke mobile heterogeneity! Two equivalent cells can have extremely divergent outcomes merely due to likelihood, with out totally different underlying biology. The truth is, we will create hundreds of equivalent “digital cells”, mannequin them with these easy guidelines, and we get the empirically-observed vary of dwell-times. There isn’t a must invoke TCR clonality or the like – it’s merely an emergent property of cells with probabilistic kinetics!
An incredible instance of utilized arithmetic informing biology!
Take a read of the pre-print here.
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