Mukherjee Sayak, Stewart David, Stewart William, Lanier Lewis L, Das Jayajit
Battelle Center for Mathematical Medicine, Research Institute at the Nationwide Children's Hospital, 700 Children's Drive, OH 43205, USA.
Institute of Bioinformatics and Applied Biotechnology, Electronic City Phase I, Bangalore, 560100India.
R Soc Open Sci. 2017 Aug 23;4(8):170811. doi: 10.1098/rsos.170811. eCollection 2017 Aug.
Single-cell responses are shaped by the geometry of signalling kinetic trajectories carved in a multidimensional space spanned by signalling protein abundances. It is, however, challenging to assay a large number (more than 3) of signalling species in live-cell imaging, which makes it difficult to probe single-cell signalling kinetic trajectories in large dimensions. Flow and mass cytometry techniques can measure a large number (4 to more than 40) of signalling species but are unable to track single cells. Thus, cytometry experiments provide detailed time-stamped snapshots of single-cell signalling kinetics. Is it possible to use the time-stamped cytometry data to reconstruct single-cell signalling trajectories? Borrowing concepts of conserved and slow variables from non-equilibrium statistical physics we develop an approach to reconstruct signalling trajectories using snapshot data by creating new variables that remain invariant or vary slowly during the signalling kinetics. We apply this approach to reconstruct trajectories using snapshot data obtained from simulations, live-cell imaging measurements, and, synthetic flow cytometry datasets. The application of invariants and slow variables to reconstruct trajectories provides a radically different way to track objects using snapshot data. The approach is likely to have implications for solving matching problems in a wide range of disciplines.
单细胞反应由信号蛋白丰度所跨越的多维空间中刻画的信号动力学轨迹的几何形状塑造。然而，在活细胞成像中检测大量（超过3种）信号分子具有挑战性，这使得在大维度上探测单细胞信号动力学轨迹变得困难。流式细胞术和质谱细胞术技术可以测量大量（4到40多种）信号分子，但无法追踪单个细胞。因此，细胞术实验提供了单细胞信号动力学的详细时间标记快照。是否可以使用时间标记的细胞术数据来重建单细胞信号轨迹？借鉴非平衡统计物理学中守恒变量和慢变量的概念，我们开发了一种方法，通过创建在信号动力学过程中保持不变或缓慢变化的新变量，利用快照数据重建信号轨迹。我们应用这种方法，使用从模拟、活细胞成像测量和合成流式细胞术数据集中获得的快照数据来重建轨迹。使用不变量和慢变量来重建轨迹，为利用快照数据追踪对象提供了一种截然不同的方法。该方法可能对解决广泛学科中的匹配问题具有启示意义。
