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Vanhaelen, Q.

Publications and source records attributed to Vanhaelen, Q..

2 recordsLinked to original sources

A note on stochastic modeling of biological systems: automatic generation of an optimized Gillespie algorithm

Signaling pathways and gene regulatory networks (GRNs) play a central role in the signal trans-duction and regulation of biochemical processes occurring within the cellular environment. Under-standing their mechanisms and dynamics is of major interest in various areas of life sciences and biological sciences. For example controlling stem cell fate decision requires a comprehension of the dynamical behavior of the networks involved in stem cell differentiation and pluripotency mainte-nance. In addition to analytical mathematical methods which are applicable for small or medium sized systems, there are many computational approaches to model and analyze the behavior of larger systems. However, from a dynamical point of view, modeling a combination of signaling pathways and GRNs present several challenges. Indeed, in addition to being of large dimensionality, these systems have specific dynamical features. Among the most commonly encountered is that the signal transduction controlled by the signaling pathways occurs at a different time scale than the transcription and translation processes. Also, stochasticity is known to strongly impact the regulation of gene expression. In this paper, we describe a simple implementation of an optimized version of the Gille-spie algorithm for simulating relatively large biological networks which include delayed reactions. The implementation presented herein comes with a script for automatically generating the different data structures and source files of the algorithm using standardized input files.\n\nCode availabilityThe Fortran90 implementation of the code and the R script described here as well as the tutorial with practical instructions are stored on the following github repository qvhaelen/ typhon

systems biology

Integrated deep learned transcriptomic and structure-based predictor of clinical trials outcomes

Despite many recent advances in systems biology and a marked increase in the availability of high-throughput biological data, the productivity of research and development in the pharmaceutical industry is on the decline. This is primarily due to clinical trial failure rates reaching up to 95% in oncology and other disease areas. We have developed a comprehensive analytical and computational pipeline utilizing deep learning techniques and novel systems biology analytical tools to predict the outcomes of phase I/II clinical trials. The pipeline predicts the side effects of a drug using deep neural networks and estimates drug-induced pathway activation. It then uses the predicted side effect probabilities and pathway activation scores as an input to train a classifier which predicts clinical trial outcomes. This classifier was trained on 577 transcriptomic datasets and has achieved a cross-validated accuracy of 0.83. When compared to a direct gene-based classifier, our multi-stage approach dramatically improves the accuracy of the predictions. The classifier was applied to a set of compounds currently present in the pipelines of several major pharmaceutical companies to highlight potential risks in their portfolios and estimate the fraction of clinical trials that were likely to fail in phase I and II.

bioinformatics