title: Decoupling global biases and local interactions between cell biological variables.
abstract: Analysis of coupled variables is a core concept of cell biological inference, with co-localization of two molecules as a proxy for protein interaction being a ubiquitous example. However, external effectors may influence the observed co-localization independently from the local interaction of two proteins. Such global bias, although biologically meaningful, is often neglected when interpreting co-localization. Here, we describe DeBias, a computational method to quantify and decouple global bias from local interactions between variables by modeling the observed co-localization as the cumulative contribution of a global and a local component. We showcase four applications of DeBias in different areas of cell biology, and demonstrate that the global bias encapsulates fundamental mechanistic insight into cellular behavior. The DeBias software package is freely accessible online via a web-server at https://debias.biohpc.swmed.edu.
authors.affiliation: Department of Cell Biology, UT Southwestern Medical Center, Dallas, United States.|Department of Bioinformatics, UT Southwestern Medical Center, Dallas, United States.
authors.forename: Assaf
authors.identifier: 0000-0002-1477-5478
authors.initials: A
authors.lastname: Zaritsky
authors.affiliation: Department of Zoology, University of Oxford, Oxford, United Kingdom.
authors.forename: Uri
authors.initials: U
authors.lastname: Obolski
authors.affiliation: Department of Cell Biology, UT Southwestern Medical Center, Dallas, United States.|Department of Bioinformatics, UT Southwestern Medical Center, Dallas, United States.
authors.forename: Zhuo
authors.identifier: 0000-0002-7738-9072
authors.initials: Z
authors.lastname: Gan
authors.affiliation: Department of Cell Biology, UT Southwestern Medical Center, Dallas, United States.
authors.forename: Carlos R
authors.initials: CR
authors.lastname: Reis
authors.affiliation: Department of Cell Biology, UT Southwestern Medical Center, Dallas, United States.
authors.forename: Zuzana
authors.initials: Z
authors.lastname: Kadlecova
authors.affiliation: Department of Bioinformatics, UT Southwestern Medical Center, Dallas, United States.
authors.forename: Yi
authors.initials: Y
authors.lastname: Du
authors.affiliation: Department of Cell Biology, UT Southwestern Medical Center, Dallas, United States.
authors.forename: Sandra L
authors.identifier: 0000-0002-1690-7024
authors.initials: SL
authors.lastname: Schmid
authors.affiliation: Department of Cell Biology, UT Southwestern Medical Center, Dallas, United States.|Department of Bioinformatics, UT Southwestern Medical Center, Dallas, United States.
authors.forename: Gaudenz
authors.identifier: 0000-0001-8583-2014
authors.initials: G
authors.lastname: Danuser
mesh_terms: D019295:Computational Biology / Q000379:methods*; D003584:Cytological Techniques / Q000379:methods*; D012984:Software; D049490:Systems Biology / Q000379:methods*
keywords: cell biology; co-localization; collective cell migration; computational biology; cytoskeleton alignment; endocytosis; global bias; local interaction; systems biology