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Lung cancer is still a leading cause of death worldwide. In recent years, knowledge has been obtained of the mechanisms modulating ion channel kinetics and thus of cell bioelectric properties, which is promising for oncological biomarkers and targets. The complex interplay of channel expression and its consequences on malignant processes, however, is still insufficiently understood. We here introduce the first approach of an in-silico whole-cell ion current model of a cancer cell, in particular of the A549 human lung adenocarcinoma, including the main functionally expressed ion channels in the plasma membrane as so far known. This hidden Markov-based model represents the electrophysiology behind proliferation of the A549 cell, describing its rhythmic oscillation of the membrane potential able to trigger the transition between cell cycle phases, and it predicts membrane potential changes over the cell cycle provoked by targeted ion channel modulation. This first A549 in-silico cell model opens up a deeper insight and understanding of possible ion channel interactions in tumor development and progression, and is a valuable tool for simulating altered ion channel function in lung cancer electrophysiology. Author summary: Advances in the understanding of functional alterations at genetic, epigenetic or protein expression and the expanding knowledge in mechanisms modulating ion channel kinetics and thus the cells' bioelectric properties have arisen as promising cancer biomarkers and oncological targets. Our hidden Markov-based in-silico cell model represents the electrophysiology behind proliferation of the A549 cell line, explaining the cell's rhythmic oscillation from hyperpolarized to depolarized states of the membrane potential, able to trigger the transition between cell cycle phases. The model enables the prediction of membrane potential changes over the cell cycle provoked by targeted modulation of specific ion channels, leading to cell cycle promotion or interruption. We are encouraged that the availability of this first cancer cell model will provide profound insight into possible roles and interactions of ion channels in tumor development and progression, and may aid in the testing of research hypotheses in lung cancer electrophysiology. [ABSTRACT FROM AUTHOR]

Metabolic biomarkers may play an important role in the diagnosis, prognostication and assessment of response to pharmacological therapy in complex diseases. The process of discovering new metabolic biomarkers is a non-trivial task which involves a number of bioanalytical processing steps coupled with a computational approach for the search, prioritization and verification of new biomarker candidates. Kinetic analysis provides an additional dimension of complexity in time-series data, allowing for a more precise interpretation of biomarker dynamics in terms of molecular interaction and pathway modulation. A novel network-based computational strategy for the discovery of putative dynamic biomarker candidates is presented, enabling the identification and verification of unexpected metabolic signatures in complex diseases such as myocardial infarction. The novelty of the proposed method lies in combining metabolic time-series data into a superimposed graph representation, highlighting the strength of the underlying kinetic interaction of preselected analytes. Using this approach, we were able to confirm known metabolic signatures and also identify new candidates such as carnosine and glycocholic acid, and pathways that have been previously associated with cardiovascular or related diseases. This computational strategy may serve as a complementary tool for the discovery of dynamic metabolic or proteomic biomarkers in the field of clinical medicine. [ABSTRACT FROM AUTHOR]