Quantitative analyses in basic, translational and clinical biomedical research: metabolism, vaccine design and preterm delivery prediction

Abstract

There is nothing more important than preserving life, and the thesis here presented is framed in the field of quantitative biomedicine (or systems biomedicine), which has as objective the application of physico-mathematical techniques in biomedical research in order to enhance the understanding of life's basis and its pathologies, and, ultimately, to defend human health. In this thesis, we have applied physico-mathematical methods in the three fundamental levels of Biomedical Research: basic, translational and clinical. At a basic level, since all pathologies have their basis in the cell, we have performed two studies to deepen in the understanding of the cellular metabolic functionality. In the first work, we have quantitatively analyzed for the first time calcium-dependent chloride currents inside the cell, which has revealed the existence of a dynamical structure characterized by highly organized data sequences, non-trivial long-term correlation that last in average 7.66 seconds, and "crossover" effect with transitions between persistent and anti-persistent behaviors. In the second investigation, by the use of delay differential equations, we have modeled the adenylate energy system, which is the principal source of cellular energy. This study has shown that the cellular energy charge is determined by an oscillatory non-stationary invariant function, bounded from 0.7 to 0.95. At a translational level, we have developed a new method for vaccine design that, besides obtaining high coverages, is capable of giving protection against viruses with high mutability rates such as HIV, HCV or Influenza. Finally, at a clinical level, first we have proven that the classic quantitative measure of uterine contractions (Montevideo Units) is incapable of predicting preterm labor immediacy. Then, by applying autoregressive techniques, we have designed a novel tool for premature delivery forecasting, based only in 30 minutes of uterine dynamics. Altogether, these investigations have originated four scientific publications, and as far as we know, our work is the first European thesis which integrates in the same framework the application of mathematical knowledge to biomedical fields in the three main stages of Biomedical Research: basic, translational and clinical.