Mathematical Biology and Ecology Seminar

Sequential biomedical data is ubiquitous, from time-resolved data about patient encounters in the clinical realm to DNA sequences in the biological domain.  The talk will review our latest work in representation learning from longitudinal data, with a particular focus on finding optimal representations for complex and sparse healthcare data. We show how these representations are useful for comparing patient journeys and finding patients with similar health outcomes. We will also venture into the field of genome engineering, where we build models that work on DNA sequences for predicting editing outcomes for base and prime editors. 

Motile cells inside living tissues often encounter junctions, where their path branches into several alternative directions of migration. We present a theoretical model of cellular polarization for cells migrating along one-dimensional lines, exhibiting diverse migration modes. When arriving at a symmetric Y-junction and extending protrusions along the different paths that emanate from the junction. The model predicts the spontaneous emergence of deterministic oscillations between competing protrusions, whereby the cellular polarization and growth alternates between the competing protrusions. These predicted oscillations are found experimentally for two different cell types, noncancerous endothelial and cancerous glioma cells, migrating on patterned network of thin adhesive lanes with junctions. Finally we present an analysis of the migration modes of multicellular "trains" along one-dimensional tracks.

Unraveling the intricacies of intracellular signalling through predictive mathematical models holds great promise for advancing precision medicine and enhancing our foundational comprehension of biology. However, navigating the labyrinth of biological mechanisms governing signalling demands a delicate balance between a faithful description of the underlying biology and the practical utility of parsimonious models.
In this talk, I will present methods that enable training of large ordinary differential equation models of intracellular signalling and showcase application of such models to predict sensitivity to anti-cancer drugs. Through illustrative examples, I will demonstrate the application of these models in predicting sensitivity to anti-cancer drugs. A critical reflection on the construction of such models will be offered, exploring the perpetual question of complexity and how intricate these models should be.
Moreover, the talk will explore novel approaches that meld machine learning techniques with mathematical modelling. These approaches aim to harness the benefits of simplistic and unbiased phenomenological models while retaining the interpretability and biological fidelity inherent in mechanistic models.
 

Malignant transformation of somatic tissues is an evolutionary process, driven by selection for oncogenic mutations. Understanding when these mutations occur, and how fast mutant cell clones expand can improve diagnostic schemes and therapeutic intervention. However, clonal dynamics are not directly accessible in humans, posing a need for inference approaches to reconstruct the division history in normal and malignant cell clones, and to predict their future evolution. Inspired from population genetics theory, we develop mathematical models to detect imprints of clonal selection in the variant allele frequency distribution measured in a single tissue sample of a homeostatic tissue. I will present the theoretical basis of our approach and inference results for the tissue dynamics in physiological and clonal hematopoiesis, obtained from variant allele frequencies measured by snapshot bulk whole genome sequencing of human bone marrow samples.

Bone regeneration processes are complex multiscale intrinsic mechanisms in bone tissue whose primary outcome is restoring function and form to a bone insufficiency. The effect of mechanics on the newly formed bone (the woven bone), is fundamental, at the tissue, cellular or even molecular scale. However, at these multiple scales, the identification of the mechanical parameters and their mechanisms of action are still unknown and continue to be investigated. This concept of mechanical regulation of biological processes is the main premise of mechanobiology and is used in this seminar to understand the multiscale response of the woven bone to mechanical factors in different bone regeneration processes: bone transport, bone lengthening and tissue engineering. The importance of a multidisciplinary approach that includes both in vivo and in silico modeling will be remarked during the seminar.