Computational analysis of circadian splicing events in human cancer cell lines and mammalian tissues
An internal time-keeping system known as the circadian clock regulates the physiology and behavior of various organisms in synchrony with daily environmental rhythms. Circadian rhythmicity of biological processes is driven by the interplay of clock genes and proteins that cause 24-h oscillations in the abundance of target gene products. The concept of chronotherapy aims at adjusting the dosingtime of drugs to the internal time of patients in order to enhance treatment efficacy and minimize toxic side effects. In recent years, a number of methods have been developed to estimate the internal time of day based on the expression of circadian genes from a small number of samples. In this talk, the ZeitZeiger (German for “time revealer”) algorithm by Hughey et al. (2016) is presented, a supervisedlearning approach that first learns a sparse representation of variation associated with the periodic variable in the training observations and then uses maximum-likelihood to predict the value of the periodic variable for a test observation. An application example from Wittenbrink et al. (2018) shows how ZeitZeiger can be used in a diagnostic tool to determine the internal circadian time of humans from a single blood sample.