Decoupling global and local relations in biased biological systems
2016
Analysis of coupled variables is a core concept of cell biological inference, with colocalization of two molecules as a proxy for protein interaction being an ubiquitous example. However, external effectors may influence the observed colocalization pattern independently from the local interaction of two proteins. Such global bias is often neglected when interpreting colocalization. Here, we describe DeBias, a computational method to quantify and decouple global bias from local interactions by modeling the observed colocalization between coupled variables as the cumulative contribution of a global and a local component. We demonstrate applications of DeBias in three areas of cell biology at different scales: Analysis of the (1) alignment of vimentin fibers and microtubules in the context of polarized cells; (2) alignment of cell velocity and traction stress during collective migration; and (3) specific recruitment of transmembrane receptors to clathrin-coated pits during endocytosis. The DeBias software package will be freely accessible online via a web-server at https://debias.biohpc.swmed.edu (pending UTSW information resources approval).
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