Projects per year
We work to understand how cancer cells can spread around the body (metastasis) and how they become resistant to treatment with drugs; these factors cause the overwhelming majority of cancer deaths. We also develop software to make sense of increasingly large datasets and to inform clinical decision-making, for example to predict which patients will respond to a particular treatment. Together, these approaches help to develop better and more effective cancer medicine.
Cells are organised and controlled by complex interactions between many individual parts (molecules), and so inherently form intricate networks. The properties of these networks underlie virtually every aspect of cell function. We map and analyse the messages passed, or information flow, amongst molecules by integrating billions of data points that describe key components such as DNA and proteins. Statistical inference, including machine learning, lets the data do the talking in order to reveal the molecular logic that controls health and disease. Indeed, computers are vital to modern biology, which interprets large datasets to gain insight into complex systems.
Main research areas:
1. Understanding molecular control and consequences of cell phenotypic plasticity in metastasis and drug resistance.
2. Developing more effective approaches for cancer patient stratification.
3. Generation of novel algorithms, techniques and computational workflows to advance the above.
Here's a short video about my research interests.
Navigating from molecular measurements to phenotype implies understanding gene function (including gene products and their products). Many genes are poorly characterised, but coordinately regulated, for example in differentiation, and new functions continue to be discovered even for deeply studied coding genes. Most noncoding genes (e.g. lncRNA, miRNA) are not well understood, nor isoforms arising from alternate splicing. Thus, a substantial portion of gene function is uncharted. Data driven networks provide useful abstractions to fill these knowledge gaps, enabling testing and generation of mechanistic hypotheses. One example current application in the group is the design of combination therapies to overcome drug resistance.
The spread of cells from a primary tumour to a secondary site remains one of the most life-threatening pathological events. Epithelial-Mesenchymal Transition (EMT) is a cell programme involving loss of cell-cell adhesion, gain of motility, invasiveness and survival; these properties are fundamental for metastasis. Epithelial remodelling is also crucial for development. Reactivation of a programme resembling EMT is a credible mechanism for key aspects of the invasion-metastasis cascade and an MET-like process may produce the differentiation frequently observed in secondary tumours. Indeed, oncofetal signalling pathways (e.g. Hedgehog, Wnt, TGF-beta) activate EMT, and promote metastasis in multiple cancers.
We have generated probabilistic systems-wide gene networks and are using these to investigate aspects of EMT/MET in different contexts; including to identify new EMT players, pathway crosstalk and drivers of metastasis. We also infer small scale causal networks combining ex vivo immunohistochemical and clinical measurements. These models integrate carefully selected data to represent the specific biological/clinical context of interest, including multiple 'omics datasets. Therefore, our work involves integration of 'big data' with machine learning and graph theoretic/statistical analyses. A wide range of techniques are employed, including supervised and unsupervised learning as well as information-theoretic approaches such as conditional mutual information. Performance is assessed by rigorous benchmarking with blind test data.
Novel algorithms are developed where required to advance biomedical understanding, for example we are working on methods towards systems-wide dynamic modelling of drug response in renal and prostate cancers. Tools developed in the group are made widely accessible (e.g. TMA Navigator). We collaborate closely with clinical colleagues and aim to translate results into medical practise.
University of Edinburgh Chancellor's Fellowship (2015)
Member of the Royal Society of Edinburgh Young Academy of Scotland (2011)
Scottish Crucible Fellow (2010)
Royal Society of Edinburgh Scottish Government Fellowship (2009)
Royal Society of Edinburgh Young Academy of Scotland Open Data working group - https://www.youngacademyofscotland.org.uk/our-work/smarter/
TMA Navigator: network inference, patient stratification and survival analysis with tissue microarray data - www.tmanavigator.org
Coordination and assessment for modules 'Dissertation Research Project' and 'Systems Medicine: From Molecules to Populations' within the Bioinformatics and Computational Genomics MSc. Lecturing to students from the following MSc courses: i) Bioinformatics and Computational Genomics, ii) Molecular Pathology of Cancer, iii) Cancer Medicine & Oncology Drug Discovery. Supervision of Postgraduate and Undergraduate Dissertation research projects and internships. Tutor for Medical Undergraduate Personal & Professional Development Portfolio.
22/04/2020 → …
06/10/2019 → …
Overton, I. M., Sims, A. H., Owen, J. A., Heale, B. S. E., Ford, M. J., Lubbock, A. L. R., Pairo-Castineira, E. & Essafi, A., 30 Sep 2020, In : Cancers. 12, 10, 34 p., 2823.
Research output: Contribution to journal › ArticleOpen AccessFile82 Downloads (Pure)
Using Simple PID-inspired Controllers for Online Resilient Resource Management of Distributed Scientific WorkflowsFerreira da Silva, R., Filgueira, R., Deelman, E., Pairo-Castineira, E., Overton, I. & Atkinson, M., Jun 2019, In : Future Generation Computing Systems. 95, p. 615-628
Research output: Contribution to journal › ArticleOpen AccessFile4 Citations (Scopus)74 Downloads (Pure)
Overcoming Intratumoural Heterogeneity for Reproducible Molecular Risk Stratification: A Case Study in Advanced Kidney CancerLubbock, A., Stewart, G., O'Mahony, F. C., Laird, A., Mullen, P., O'Donnell, M., Powles, T., Harrison, D. J. & Overton, I., 26 Jun 2017, In : BMC Medicine. 15, 118.
Research output: Contribution to journal › ArticleOpen AccessFile4 Citations (Scopus)177 Downloads (Pure)
Quantitative Shotgun Proteomics Unveils Candidate Novel Esophageal Adenocarcinoma (EAC)-specific ProteinsO'neill, J. R., Pak, H-S., Pairo-Castineira, E., Save, V., Paterson-Brown, S., Nenutil, R., Vojtěšek, B., Overton, I., Scherl, A. & Hupp, T. R., 01 Mar 2017, In : Molecular and Cellular Proteomics. 16, 6, p. 1138-1150
Research output: Contribution to journal › ArticleOpen AccessFile6 Citations (Scopus)201 Downloads (Pure)
Overton, I. & Atkinson, M., 14 Nov 2016, Workflows in Support of Large-Scale Science: Proceedings of the 11th Workshop on Workflows in Support of Large-Scale Science co-located with The International Conference for High Performance Computing, Networking, Storage and Analysis (SC 2016). Vol. 1802. p. 15-24 (CEUR Workshop Proceedings).
Research output: Chapter in Book/Report/Conference proceeding › Conference contributionOpen AccessFile5 Citations (Scopus)108 Downloads (Pure)