TimeTeller: a New Tool for Precision Circadian Medicine and Cancer Prognosis
Vlachou, D.; Bjarnason, G. A.; Giacchetti, S.; Levi, F.; Rand, D. A.
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Recent studies have established that the circadian clock influences onset, progression and therapeutic outcomes in a number of diseases including cancer and heart disease. Therefore, there is a need for tools to measure the functional state of the circadian clock and its downstream targets in patients. We provide such a tool and demonstrate its clinical relevance by an application to breast cancer where we find a strong link between survival and our measure of clock dysfunction. We use a machine-learning approach and construct an algorithm called TimeTeller which uses the multi-dimensional state of the genes in a transcriptomics analysis of a single biological sample to assess the level of circadian clock dysfunction. We demonstrate how this can distinguish healthy from malignant tissues and demonstrate that the molecular clock dysfunction metric is a potentially new prognostic and predictive breast cancer biomarker that is independent of the main established prognostic factors.
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