SBL Featured Publications

Human skin as a model for signalling during cellular differentiation

A central research theme within the Systems Biology Laboratory is investigating how cells use molecular mechanisms to control tissue function. Read More ›

Modelling the conditional regulatory activity of methylated and bivalent promoters

This project builds upon our previous work modelling gene expression from epigenetic data to model 'conditional' regulatory activity; we also provide the first genome-wide integration of DNA methylation bisulfite-sequencing data within such a model to substantially improve prediction accuracy and the reliability of downstream biological inference. Read More ›

Predictive modelling of gene expression from transcriptional regulatory elements

Predictive modelling is a powerful in silico framework for exploring the regulatory interactions between the epigenetic and transcriptomic layers. Unlike network-based analyses that model genes as variables in an underdetermined system, these models treat genes as observations to allow statistically-significant insights to be gained regarding the complementary roles of histone modifications, transcription factors, DNA methylation and other key regulators. This study provides the first critical review of several epigenetic feature extraction and predictive modelling techniques across multiple cell lines and organisms. Read More ›

Predicting expression: the complementary power of histone modification and transcription factor binding data

Statistical redundancy between epigenetic features is a critical issue in predictive gene expression modelling. Redundancy between histone modification and transcription factor binding data prevents their effective integration within a single model, reducing prediction accuracy and reliability of downstream biological inference. This study provides a detailed analysis of the biological phenomena underlying redundancy both within and between these epigenetic regulators, providing new insights into spatiotemporal gene regulation and laying the foundation for improved modelling frameworks. Read More ›

Virtual Reference Environments: a simple way to make research reproducible

'Reproducible research' has received increasing attention over the past few years as bioinformatics and computational biology methodologies become more complex. Although reproducible research is progressing in several valuable ways, we suggest that recent increases in internet bandwidth and disk space, along with the availability of open-source and free-software licences for tools, enable another simple step to make research reproducible. In this article, we urge the creation of minimal virtual reference environments implementing all the tools necessary to reproduce a result, as a standard part of publication. We address potential problems with this approach, and show an example environment from our own work. Read More ›

The flavoprotein FOXRED2 reductively activates nitro-chloromethylbenzindolines and other hypoxia-targeting prodrugs

Hypoxia is a prevalent feature of solid malignancies that arises as a result of structural and functional irregularities in tumour microvasculature. In this work, we built correlation and partial correlation networks from microarray data to identify enzymes which convert hypoxia-activated prodrugs (HAPs) to their active form. Read More ›

Links between the Oncoprotein YB-1 and Small Non-Coding RNAs in Breast Cancer

The nucleic acid-binding protein YB-1, a member of the cold-shock domain protein family, has been implicated in the progression of breast cancer and is associated with poor patient survival. YB-1 has sequence similarity to LIN28, another cold-shock protein family member, which has a role in the regulation of small noncoding RNAs (sncRNAs) including microRNAs (miRNAs). Therefore, to investigate whether there is an association between YB-1 and sncRNAs in breast cancer, we investigated whether sncRNAs were bound by YB-1 in two breast cancer cell lines (luminal A-like and basal cell-like), and whether the abundance of sncRNAs and mRNAs changed in response to experimental reduction of YB-1 expression. Read More ›