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Berners-Lee, R.

Publications and source records attributed to Berners-Lee, R..

2 recordsLinked to original sources

Bootstrap-based criteria for identifying differences between learned Bayesian networks

Bayesian networks provide a powerful framework for learning dependencies from data, and they are widely used to probe structure in biological systems. Biological systems are governed by complex networks of interactions, and uncovering these interactions and comparing them across conditions is central to understanding biological mechanisms. However, when comparing Bayesian networks, it can be difficult to determine whether observed differences are substantial enough to reflect genuine differences in the underlying systems generating the data. Here, we address this by developing bootstrap-based criteria for identifying such differences and demonstrate their performance using simulated data from synthetic Bayesian networks. Both edge-level and whole-network connectivity comparisons reliably identified when underlying networks differed, even when this involved only 5% of edges, while distinguishing these differences from sampling variation. However, even with large datasets, the criteria were unable to recover specific edge differences. Thus distinguishing that networks differed was possible, but not the specific ways they differed. These criteria establish a framework for more robust and standardised Bayesian network comparisons, with broad potential for real-world applications.

systems biology↗

Regulation of replication timing in Saccharomyces cerevisiae

In order to maintain genomic integrity, DNA replication must be highly coordinated. Disruptions in this process can cause replication stress which is aberrant in many pathologies including cancer. Despite this, little is known about the mechanisms governing the temporal regulation of DNA replication initiation, thought to be related to the limited copy number of firing factors. Here, we present a high (1-kilobase) resolution stochastic model of Saccharomyces cerevisiae whole-genome replication in which origins compete to associate with limited firing factors. After developing an algorithm to fit this model to replication timing data, we validated the model by reproducing experimental inter-origin distances, origin efficiencies, and replication fork directionality. This suggests the model accurately simulates the aspects of DNA replication most important for determining its dynamics. We also use the model to predict measures of DNA replication dynamics which are yet to be determined experimentally and investigate the potential impacts of variations in firing factor concentrations on DNA replication.

systems biology↗