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Michael Adamer

Publications and source records attributed to Michael Adamer.

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Genetic prediction of quantitative traits: a machine learner's guide focused on height

Machine learning and deep learning have been celebrating many successes in the application to biological problems, especially in the domain of protein folding. Another equally complex and important question has received relatively little attention by the machine learning community, namely the one of prediction of complex traits from genetics. Tackling this problem requires in-depth knowledge of the related genetics literature and awareness of various subtleties associated with genetic data. In this guide, we provide an overview for the machine learning community on current state of the art models and associated subtleties which need to be taken into consideration when developing new models for phenotype prediction. We use height as an example of a continuous-valued phenotype and provide an introduction to benchmark datasets, confounders, feature selection, and common metrics.

cs.LG

Algebraic study of receptor-ligand systems: a dose-response analysis

The study of a receptor-ligand system generally relies on the analysis of its dose-response (or concentration-effect) curve, which quantifies the relation between ligand concentration and the biological effect (or cellular response) induced when binding its specific cell surface receptor. Mathematical models of receptor-ligand systems have been developed to compute a dose-response curve under the assumption that the biological effect is proportional to the number of ligand-bound receptors. Given a dose-response curve, two quantities (or metrics) have been defined to characterise the properties of the ligand-receptor system under consideration: amplitude and potency (or half-maximal effective concentration, and denoted by EC$_{50}$). Both the amplitude and the EC$_{50}$ are key quantities commonly used in pharmaco-dynamic modelling, yet a comprehensive mathematical investigation of the behaviour of these two metrics is still outstanding; for a large (and important) family of receptors, called cytokine receptors, we still do not know how amplitude and EC$_{50}$ depend on receptor copy numbers. Here we make use of algebraic approaches (Gr\"obner basis) to study these metrics for a large class of receptor-ligand models, with a focus on cytokine receptors. In particular, we introduce a method, making use of two motivating examples based on the interleukin-7 (IL-7) receptor, to compute analytic expressions for the amplitude and the EC$_{50}$. We then extend the method to a wider class of receptor-ligand systems, sequential receptor-ligand systems with extrinsic kinase, and provide some examples.

q-bio.MN