Analysis of timeseries data with hidden components

Jae Kyoung Kim (May 5, 2020)

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Despite dramatic advances in experimental techniques, many facets of intracellular dynamics remain hidden, or can be measured only indirectly. In this talk, I will describe three strategies to analyze timeseries data from biological systems with hidden parts: replacement of hidden components with either time delay, quasi-steady-state or random regulatory process. Then, I will illustrate how the simplification with the time delay can be used to understand the processes of protein synthesis, which involves multiple steps such as transcription, translation, folding and maturation, but typically whose intermediates proteins cannot be measured. Furthermore, I will illustrate how the simplification with the quasi-steady-state can be used to develop an accurate method to estimate drug clearance, which occurs in multiple steps of metabolism, which greatly improved the canonical approach used in more than 65,000 published papers for last 30 years. Finally, I will describe a systematic modeling selection approach to identify hidden regulatory biochemical connections leading to the observed timeseries data. Then, I will illustrate how we applied the approach to find the connection between the circadian clock and cell cycle checkpoints.