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Guy Karlebach

Publications and source records attributed to Guy Karlebach.

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Optimal Inference of Asynchronous Boolean Network Models

The network inference problem arises in biological research when one wishes to explain a phenotype using a network of interactions between molecules. The diverse nature of the data and nonlinear dynamics of the network pose significant challenges in choosing the best model. In addition to balancing fit and model size, computational efficiency must be considered. The latter constitutes a central consideration for the researcher since underlying the measurements, which are affected by experimental noise, there is a complex computational mechanism that may be asynchronous and is inherently hard to identify. To address these challenges, we present a novel approach that uses algorithmic complexity to infer an asynchronous Boolean network model from experimental data. We present an algorithm that is optimal within this framework and allows for asynchronicity in network dynamics. Results are described for real data, a literature-derived network and random networks.

q-bio.MN

A Novel Algorithm for the Maximal Fit Problem in Boolean Networks

Gene regulatory networks (GRNs) are increasingly used for explaining biological processes with complex transcriptional regulation. A GRN links the expression levels of a set of genes via regulatory controls that gene products exert on one another. Boolean networks are a common modeling choice since they balance between detail and ease of analysis. However, even for Boolean networks the problem of fitting a given network model to an expression dataset is NP-Complete. Previous methods have addressed this issue heuristically or by focusing on acyclic networks and specific classes of regulation functions. In this paper we introduce a novel algorithm for this problem that makes use of sampling in order to handle large datasets. Our algorithm can handle time series data for any network type and steady state data for acyclic networks. Using in-silico time series data we demonstrate good performance on large datasets with a significant level of noise.

q-bio.MN