Detection of Specific Templates in Calcium Spiking in HeLa Cells Using Hierarchical DBSCAN: Clustering and Visualization of CellDrug Interaction at Multiple Doses

One of the major challenges in analyzing large scale intracellular calcium spiking data obtained through fluorescent imaging is to identify various patterns present in time series data. Such an analysis identifying the distinct frequency and amplitude encoding during cell-drug interaction study is expected to provide new insights into the drug action patterns over a time course. Here, we present the HDBSCAN clustering algorithm to find a clustering pattern present in calcium spiking obtained by confocal imaging of single cells. Our methodology uncovers the specific templates present in dynamic responses obtained through treatment with multiple doses of the drug. First, we attempt to visualize the clustering pattern present in time-series data corresponding to various doses of the drug. Secondly, we show that the HDBSCAN can be used for the detection of specific signatures corresponding to low and high cell density regions selected from in vitro experiments. To the best of our knowledge, this is the first attempt to optimize the clustering of calcium dynamics using HDBSCAN. Finally, we emphasize that HDBSCAN offers a high-level grasp on systems biology data, including complex spiking pattern and can be used as a visual analytic tool for drug dose selection.