Shooting movies of signaling network dynamics with multiparametric cytometry

Abstract

Single-cell technologies like mass cytometry enable researchers to comprehensively monitor signaling network responses in the context of heterogeneous cell populations. Cell-to-cell variability, the possibly nonlinear topology of signaling processes, and the destructive nature of mass cytometry necessitate nontrivial computational approaches to reconstruct and sensibly describe signaling dynamics. Modeling of signaling states depends on a set of coherent examples, that is, a set of cell events representing the same cell state. This requirement is frequently compromized by process asynchrony phenomena or nonlinear process topologies. We discuss various computational deconvolution approaches to define molecular process coordinates and enable compilation of coherent data sets for cell state inference. In addition to the conceptual presentation of these approaches, we discuss the application of these methods to modeling of TRAIL-induced apoptosis. Due to their generic applicability these computational approaches will contribute to the elucidation of dynamic intracellular signaling networks in various settings. The resulting signaling maps constitute a promising source for novel interventions and are expected to be particularly valuable in clinical settings.