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Biology subjects

Jack Kuipers

Publications and source records attributed to Jack Kuipers.

2 recordsLinked to original sources

The Influence of Canalization on the Robustness of Boolean Networks

Time- and state-discrete dynamical systems are frequently used to model molecular networks. This paper provides a collection of mathematical and computational tools for the study of robustness in Boolean network models. The focus is on networks governed by k-canalizing functions, a recently introduced class of Boolean functions that contains the well-studied class of nested canalizing functions. The activities and sensitivity of a function quantify the impact of input changes on the function output. This paper generalizes the latter concept to c-sensitivity and provides formulas for the activities and c-sensitivity of general k-canalizing functions as well as canalizing functions with more precisely defined structure. A popular measure for the robustness of a network, the Derrida value, can be expressed as a weighted sum of the c-sensitivities of the governing canalizing functions, and can also be calculated for a stochastic extension of Boolean networks. These findings provide a computationally efficient way to obtain Derrida values of Boolean networks, deterministic or stochastic, that does not involve simulation.

Biophysics

Tree inference for single-cell data

Understanding the mutational heterogeneity within tumours is a keystone for the development of efficient cancer therapies. Here, we present SCITE, a stochastic search algorithm to identify the evolutionary history of a tumour from noisy and incomplete mutation profiles of single cells. SCITE comprises a exible MCMC sampling scheme that allows the user to compute the maximum-likelihood mutation history, to sample from the posterior probability distribution, and to estimate the error rates of the underlying sequencing experiments. Evaluation on real cancer data and on simulation studies shows the scalability of SCITE to present-day single-cell sequencing data and improved reconstruction accuracy compared to existing approaches.

Cancer Biology