Bayesian matrix factorization for drug discovery and precision medicine

EVENT : C3BI Seminars


Main speaker : Yves Moreau, from Center for Computational Systems Biology, KU Leuven Date : 31-01-2019 at 02:00 pm Location : Auditorium Francois Jacob – BIME (26) ,Institut Pasteur, Paris


Matrix factorization/completion methods provide an attractive framework to handle sparsely observed data, also called “scarce” data. A typical setting for scarce data are is clinical diagnosis in a real-world setting. Not all possible symptoms (phenotype/biomarker/etc.) will have been checked for every patient. Deciding which symptom to check based on the already available information is at the heart of the diagnostic process. If genetic information about the patient is also available, it can serve as side information (covariates) to predict symptoms (phenotypes) for this patient. While a classification/regression setting is appropriate for this problem, it will typically ignore the dependencies between different tasks (i.e., symptoms). We have recently focused on a problem sharing many similarities with the diagnostic task: the prediction of biological activity of chemical compounds against drug targets, where only 0.1% to 1% of all compound-target pairs are measured. Matrix factorization searches for latent representations of compounds and targets that allow an optimal reconstruction of the observed measurements. These methods can be further combined with linear regression models to create multitask prediction models. In our case, fingerprints of chemical compounds are used as “side information” to predict target activity. By contrast with classical Quantitative Structure-Activity Relationship (QSAR) models, matrix factorization with side information naturally accommodates the multitask character of compound-target activity prediction. This methodology can be further extended to a fully Bayesian setting to handle uncertainty optimally, and our reformulation allows scaling up this MCMC scheme to millions of compounds, thousands of targets, and tens of millions of measurements, as demonstrated on a large industrial data set from a pharmaceutical company. We also show applications of this methodology to the prioritization of candidate disease genes and to the modeling of longitudinal patient trajectories. We have implemented our method as an open source Python/C++ library, called Macau, which can be applied to many modeling tasks, well beyond our original pharmaceutical setting. https://github.com/jaak-s/macau/tree/master/python/macau.


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