Computational Modelling Group

Bioinformatics

Bioinformatics is the storage, manipulation and processing of biological data using computers. This topic includes all modelling of "omics" data - genomics (DNA), proteomics (protein), transcriptomics (mRNA), metabolomics (metabolites) etc. - as well as "classical" sequence analysis (multiple sequence alignment, homology searching, phylogenetic etc.). Bioinformatics projects will usually make use of in vitro and/or in vivo experimental data. For informal bioinformatics discussion/networking at Southampton, please visit the UoS Bioinformatics facebook group.

For queries about this topic, contact Richard Edwards.

View the calendar of events relating to this topic.

Projects

A composite likelihood approach to genome-wide data analyses.

Andrew Collins (Investigator), Jane Gibson, Ioannis Politopoulos

We describe composite likelihood-based analysis of a genome-wide breast cancer case-control sample by determining genome regions of fixed size on a linkage disequilibrium map which delimit comparable levels of linkage disequilibrium. Analysis of findings suggests further validation in more samples from other cohorts as well as the exploitation of novel computationally-intensive methods such as next-generation sequencing.

Antimicrobial Peptide and E. coli Membrane Interactions

Syma Khalid (Investigator), Thomas Piggot, Nils Berglund

Antimicrobial peptides (AMPs) are known to disrupt the membranes of bacterial cells such as E. coli. I work on investigating the nature of these interactions using molecular dynamics (MD) simulations.

Application of RNA-Seq for gene fusion identification in blood cancers

William Tapper (Investigator), Marcin Knut

Gene fusions are often the cause of different blood cancers. As such, accurate identification of them provides information on the underlying cause of a cancer, ensuring appropriate choice of treatment. However, due to shortcomings of the currently applied methods for gene fusion identification, some of them escape undetected. We are employing RNA-Seq, a cutting-edge method for sequencing RNA, the messenger of genetic information, to investigate gene fusions.

Benchmarking the GOPHER orthologue prediction algorithm.

Richard Edwards, Shaun Maguire

Generation of Orthologous Proteins from High-throughput Evolutionary Relationships (GOPHER) is an orthologue prediction algorithm. This experiment aims to benchmark this algorithm.

Bioinformatic identification and physiological analysis of ethanol-related genes in C. elegans

Richard Edwards, Vincent O'Connor, Lindy Holden-Dye (Investigators), Ben Ient

Investigating the broad molecular, cellular and systems level impacts of acute and chronic ethanol in the nematode, Caenorhabditis elegans, as a model.

Can we calculate the pKa of new drugs, based on their structure alone?

Chris-Kriton Skylaris (Investigator), Chris Pittock, Jacek Dziedzic

The pKa of an active compound in a pharmaceutical drug affects how it is absorbed and distributed around the human body. While there are various computational methods to predict pKa using only molecular structure data, these tend to be specialised to only one class of drug - we aim to generate a more generalised prediction method using quantum mechanics.

Centre for Doctoral Training in Next Generation Computational Modelling

Hans Fangohr, Ian Hawke, Peter Horak (Investigators), Susanne Ufermann Fangohr, Ryan Pepper, Hossam Ragheb, Emanuele Zappia, Ashley Setter, David Lusher, Alvaro Perez-Diaz, Kieran Selvon, Thorsten Wittemeier, Mihails Milehins, Stephen Gow, Ioannis Begleris, Jonathon Waters, James Harrison, Joshua Greenhalgh, Rory Brown, Robert Entwistle, Paul Chambers, Jan Kamenik, Craig Rafter

The £10million Centre for Doctoral Training was launched in November 2013 and is jointly funded by EPSRC, the University of Southampton, and its partners.

The NGCM brings together world-class simulation modelling research activities from across the University of Southampton and hosts a 4-year doctoral training programme that is the first of its kind in the UK.

Deep Optimisation

Jamie Caldwell

The project will develop the implementation and application of a new optimisation technique. 'Deep optimisation' combines deep learning techniques in neural networks with distributed optimisation methods to create a dynamically re-scalable optimisation process. This project will develop this technique to better-understand its capabilities and limitations and develop GPU implementations. The protein structure prediction problem will be used as the main test application.

E ffects of Sample Contamination on Alternate Allele Frequency

Jane Gibson (Investigator), Roshan Sood

Accurate calling of genetic variants is reliant on the purity of samples, contamination will reduce the accuracy of results. Currently there are few programs able to identify contamination in samples, potentially misinforming a researcher or clinician. To better understand the changes caused by sample contamination in
silico simulations were performed where a known percentage of DNA sequence reads from a contaminating
fi le were added. Understanding the changes will assist the development of a new method and program to
detect sample contamination.

Genetic studies to characterise the role of genetic factors in early-onset breast cancer

Andrew Collins (Investigator), Rosanna Upstill-Goddard

Breast cancer is a highly heterogeneous disease, with many distinct subtypes. In the majority of breast cancer cases the causative genetic component is poorly characterised. This study aims to explore both rare and common mutations in early-onset breast cancer patients and the contribution of such variants to disease using a variety of analytic approaches.

Identification of Gene-Modules Associated to a Predisposition of Post-Traumatic Stress Disorder

Christopher Woelk (Investigator), Michael Breen

The predisposing genetic factors associated to Post-Traumatic Stress Disorder (PTSD) are altogether unknown. Since not all trauma-survivors later develop the PTSD, it has been hypothesized that transcript differentiation prior–to-trauma exposure could be associated to the risk and resilience of PTSD. We apply a systems-level approach to investigate changes in transcript abundance (gene expression profiles) in whole blood of U.S. Marines sampled prior-to-deployment to the battlefield and followed through-out a seven month deployment to obtain disorder related outcomes.

Identification of novel Crustacean Pathogen Receptor Proteins

Richard Edwards, Chris Hauton, Timothy Elliott (Investigators), Oyindamola Lawal, Lloyd Mushambadzi

We are mining EST libraries (sequence fragments of expressed genes) for novel proteins that might play a role in the immune response of crustaceans.

Identification of phage DNA, common insertion sites and their effect on genes within S.pneumoniae

Richard Edwards, Amy Dean

This study seeks to find if there are any common insertion sites across different strains of S.pneumoniae and discover genes that undergo frequent mutation due to phages and if these mutations can be linked to virulence of the strains.

Identifying factors required for DNA methylation using the imprinting control protein ZFP57

Deborah Mackay (Investigator)

Mutation of ZFP57 in humans is associated with widespread loss of DNA methylation at imprinted genes, and clinical features including congenital anomalies and developmental delay (Mackay et al, 08). This indicates that ZFP57 is required for DNA methylation of imprinted genes necessary for normal development.
We propose to identify the DNA sequences targeted by ZFP57, and its protein cofactors. This work will give insight into the biology of imprinting, indicate mechanisms of disease, and identify novel imprinted genes.

Identifying variants in next generation sequencing data of 61 paediatric Inflammatory Bowel Disease patients

Sarah Ennis (Investigator), Gaia Andreoletti

This study aims to characterise the mutations of genes known to predispose Inflammatory bowel disease in 61 paediatric patients using next generation sequencing analysis. Our aim is to identify the relative impact of known genes in individual case presentations of disease and correlate matches with clinical manifestation.

Immunotherapy Research: Modelling MHC Class I Complex Assembly

Timothy Elliott, Jorn Werner (Investigators), Alistair Bailey

This project uses mathematical modelling and simulation to investigate mechanisms by which our cells process and present biological information that is used by our immune system to distinguish between healthy and diseased cells.

Integrated in silico prediction of protein-protein interaction motifs

Richard Edwards (Investigator), Nicolas Palopoli, Kieren Lythgow

Many vital protein-protein interactions are mediated by Short Linear Motifs (SLiMs) which are short proteins typically 5-15 amino acids long containing only a few positions crucial to function. This project integrates a number of leading computational techniques to predict novel SLiMs and add crucial detail to protein-protein interaction networks.

Interactome-wide prediction of short linear protein interaction motifs in humans

Richard Edwards (Investigator)

Short Linear Motifs (SLiMs) are important in many protein-protein interactions. In previous work, we have developed a computational tool, SLiMFinder, which places the interpretation of evidence for motifs within a statistical framework with high specificity, and subsequently enhanced sensitivity through application of conservation-based sequence masking. We are now applying these tools to a comprehensive set of human protein-protein interactions in order to predict novel human SLiMs in silico.

Mass Spec identification of proteins utilising EST libraries

Richard Edwards, Maria Debora Iglesias-Rodriguez (Investigators), Bethan Jones

Expressed Sequence Tag (EST) data presents a particular challenge for the identification of proteins using mass spectrometry (MS): it is often redundant (multiple copies of the same gene), consists primarily of short fragments of coding sequence, contains many sequencing errors and is generally poorly annotated. We are developing computational pipelines to maximise robust protein identifications from EST data despite these challenges.

Metagenomics: Understanding the impacts of environmental change on soil biodiversity

Richard Edwards, Gail Taylor (Investigators), Joseph Jenkins

Drought is expected to increase in prevalence by 2050. Similarly, the use of biochar (a charcoal based soil amendment) has been suggested as a method to sequester carbon and fertilize soils without need of mineral fertilizers, and its use is increasing. We are using next generation DNA sequencing technology and bioinformatics to determine bacterial genetic diversity from soil samples which have been subject to drought or biochar amendment, to further our understanding of the impacts of environmental change on microbial communities.

Modelling Macro-Nutrient Release & Fate Resulting from Sediment Resuspension in Shelf Seas

Chris Wood

This study involves adapting a previously-published model to take into account the effect resuspension events (both natural and anthropogenic) may have on nutrient dynamics at the sediment-water interface, and hence produce better estimates for the total nutrient budgets for shelf seas.

Multi-scale simulations of bacterial outer-membrane proteins

Syma Khalid (Investigator), Jamie Parkin

Using Iridis to run multiple simulations, I aim to simulate the outer membrane proteins of Pseudomonas aeruginosa, using X-ray crystal structures of proteins only recently resolved by Bert van den Berg, University of Massachusetts. By modelling the proteins in a realistic P. aeruginosa outer membrane, I aim to gain insight into the binding of these proteins to specific substrates and their function.

Multiscale Modelling of Cellular Calcium Signalling

Hans Fangohr, Jonathan Essex (Investigators), Dan Mason

Calcium ions play a vitally important role in signal transduction and are key to many cellular processes including muscle contraction and cell apoptosis (cell death). This importance has made calcium an active area in biomedical science and mathematical modelling.

New Forest Cicada Project

Alexander Rogers, Geoff Merrett (Investigators), Davide Zilli, Oliver Parson

Rediscover the critically endangered New Forest cicada with crowdsourced smartphone biodiversity monitoring techniques.

Sample tracking in whole-exome sequencing projects

Andrew Collins, Sarah Ennis (Investigators), Reuben Pengelly

Whole-exome sequencing is entering clinical use for genetic investigations, and it is therefore essential that robust quality control is utilised. As such we designed and validated a tool to allow for unambiguous tying of patient data to a patient, to identify, and thus prevent errors such as the switching of samples during processing.

Sensitivity of the critical depth to the choice of particle movement rules in Lagrangian models and the consequences for the predicted timing of the spring bloom

Tom Anderson (Investigator), Melissa Saeland

Individual-based (Lagrangian) models lend themselves to the study of the controls of the spring bloom in the ocean, due to their ability to represent both the turbulence and the phytoplankton motion. Here, we use a Lagrangian phytoplankton model to test some of the most prevalent hypotheses (e.g. critical depth and critical turbulence).

Simulation of biological systems at long length and distance scales

Jonathan Essex (Investigator), Kieran Selvon

This project aims to shed light on cell membrane mechanisms which are difficult to probe experimentally, in particular drug permiation across the cell membrane. If one had a full understanding of the mechanism, drugs could be designed to target particular embedded proteins to improve their efficacy, the viability of nano based medicines and materials could also be assessed, testing for toxicity etc.

Studying microevolution in clinical isolates of Neisseria lactamica

Robert Read (Investigator), Jay Laver, Anish Pandey

We intranasally infected and successfully colonised six volunteers with Neisseria lactamica, a commensal species genetically similar to Neisseria meningitidis. A bioinformatics approach was then used to understand the microevolution of this bacterium and its adaptations to the nasopharynx.

Tag based transcriptome analysis of gene expression in a promising green algae

Richard Edwards (Investigator), Andreas Johansson

We use SuperSAGE in combination with next-generation sequencing to compare differences in gene expression between selected mutants and the wild type of a green algae. The data in the form of millions of 26 bp tags representing short stretches of expressed genes, will be analysed to find patterns of variation in gene expression under different conditions.

The application of next-generation sequencing to unresolved familial disease

Andrew Collins, Sarah Ennis (Investigators), Jane Gibson, Reuben Pengelly

Next-generation sequencing (NGS) allows us to sequence individual patients cost-effectively, allowing us to enter a new era of genomic medicine. The level of genetic detail that we can access through these methods is unprecedented making it suitable for clinical molecular diagnostics.

The tarsal intersegmental reflex control system in the locust hind leg

David Simpson, Philip Newland (Investigators), Alicia Costalago Meruelo

Locomotion is vital for vertebrates and invertebrates to survive. Despite that feet are responsible for stability and agility in most animals, research on feet movements and their reflexes is scarce.
In this thesis, the tarsal reflex responses of locust will be studied and modelled with ANNs to achieve a deeper comprehension of how stability and agility is accomplished.
The choice of ANNs is linked to the applicability of the method into other fields, such as technological designs or medical treatment.

Transgenerational inheritance of allergy in a multi generational cohort

John Holloway (Investigator)

The aim of this project is to determine the vertical transmission of DNA methylation by identification of CpG sites by microarray analysis of 450,000 CpG sites in 252 women of the IoW cohort that are associated with allergic sensitization and testing whether the identified methylation patterns are vertically transmitted to their offspring and whether modifiable environmental conditions during gestation affect DNA methylation.

Water Molecules in Protein Binding Sites

Jonathan Essex (Investigator), Michael Bodnarchuk

Water molecules are commonplace in protein binding sites, although the true location of them can often be hard to predict from crystallographic methods. We are developing tools which enable the location and affinity of water molecules to be found.

Whole exome sequencing identifies novel FLNA mutation in familial Ebstein's anomaly

Jane Gibson, Andrew Collins, Sarah Ennis (Investigators), Gaia Andreoletti

We describe the application of whole-exome sequencing in a family in which eight people in three generations presented Ebstein's anomaly.

People

Andrew Collins
Professor, Medicine (FM)
Timothy Elliott
Professor, Medicine (FM)
Sarah Ennis
Professor, Medicine (FM)
Jonathan Essex
Professor, Chemistry (FNES)
Hans Fangohr
Professor, Engineering Sciences (FEE)
Lindy Holden-Dye
Professor, Biological Sciences (FNES)
John Holloway
Professor, Medicine (FM)
Philip Newland
Professor, Biological Sciences (FNES)
Anthony Postle
Professor, Medicine (FM)
Robert Read
Professor, Medicine (FM)
Gail Taylor
Professor, Biological Sciences (FNES)
Karen Temple
Professor, Medicine (FM)
Peter Horak
Reader, Optoelectronics Research Centre
Deborah Mackay
Reader, Medicine (FM)
Vincent O'Connor
Reader, Biological Sciences (FNES)
Tiina Roose
Reader, Engineering Sciences (FEE)
Jorn Werner
Reader, Biological Sciences (FNES)
Thomas Blumensath
Senior Lecturer, Institute of Sound & Vibration Research (FEE)
Stuart Clarke
Senior Lecturer, Medicine (FM)
Robert Ewing
Senior Lecturer, Biological Sciences (FNES)
David Simpson
Senior Lecturer, Institute of Sound & Vibration Research (FEE)
Christopher Bell
Lecturer, Biological Sciences (FNES)
Srinandan Dasmahapatra
Lecturer, Electronics and Computer Science (FPAS)
Jane Gibson
Lecturer, Biological Sciences (FNES)
Ian Hawke
Lecturer, Mathematics (FSHS)
Maria Debora Iglesias-Rodriguez
Lecturer, Ocean & Earth Science (FNES)
Geoff Merrett
Lecturer, Electronics and Computer Science (FPAS)
Alexander Rogers
Lecturer, Electronics and Computer Science (FPAS)
Paul Skipp
Lecturer, Biological Sciences (FNES)
Chris-Kriton Skylaris
Lecturer, Chemistry (FNES)
Tom Anderson
Principal Research Fellow, National Oceanography Centre (FNES)
Syma Khalid
Principal Research Fellow, Chemistry (FNES)
Chris Hauton
Senior Research Fellow, Ocean & Earth Science (FNES)
Jay Laver
Senior Research Fellow, Medicine (FM)
Philip Williamson
Senior Research Fellow, Biological Sciences (FNES)
Alistair Bailey
Research Fellow, Medicine (FM)
Jacek Dziedzic
Research Fellow, Chemistry (FNES)
Johanna Jefferies
Research Fellow, Medicine (FM)
Reuben Pengelly
Research Fellow, Medicine (FM)
Roxana Aldea
Postgraduate Research Student, Mathematics (FSHS)
Gaia Andreoletti
Postgraduate Research Student, Medicine (FM)
Ioannis Begleris
Postgraduate Research Student, Engineering Sciences (FEE)
Michael Bodnarchuk
Postgraduate Research Student, Chemistry (FNES)
Louise Bolton
Postgraduate Research Student, Medicine (FM)
Michael Breen
Postgraduate Research Student, Medicine (FM)
Rory Brown
Postgraduate Research Student, Civil Engineering & the Environment (FEE)
Jamie Caldwell
Postgraduate Research Student, Engineering Sciences (FEE)
Paul Chambers
Postgraduate Research Student, Engineering Sciences (FEE)
Alicia Costalago Meruelo
Postgraduate Research Student, University of Southampton
Caroline Duignan
Postgraduate Research Student, Biological Sciences (FNES)
Robert Entwistle
Postgraduate Research Student, Engineering Sciences (FEE)
Ric Gillams
Postgraduate Research Student, Chemistry (FNES)
Rebecca Gladstone
Postgraduate Research Student, Medicine (FM)
Stephen Gow
Postgraduate Research Student, Engineering Sciences (FEE)
Joshua Greenhalgh
Postgraduate Research Student, Engineering Sciences (FEE)
James Harrison
Postgraduate Research Student, Engineering Sciences (FEE)
Guy Jacobs
Postgraduate Research Student, Electronics and Computer Science (FPAS)
Joseph Jenkins
Postgraduate Research Student, Biological Sciences (FNES)
Andreas Johansson
Postgraduate Research Student, National Oceanography Centre (FNES)
Bethan Jones
Postgraduate Research Student, National Oceanography Centre (FNES)
Jan Kamenik
Postgraduate Research Student, Engineering Sciences (FEE)
Marcin Knut
Postgraduate Research Student, Medicine (FM)
David Lusher
Postgraduate Research Student, Engineering Sciences (FEE)
Anish Pandey
Postgraduate Research Student, Medicine (FM)
Gregory Parkes
Postgraduate Research Student, Engineering Sciences (FEE)
Jamie Parkin
Postgraduate Research Student, Chemistry (FNES)
Alvaro Perez-Diaz
Postgraduate Research Student, Engineering Sciences (FEE)
Can Pervane
Postgraduate Research Student, Electronics and Computer Science (FPAS)
Chris Pittock
Postgraduate Research Student, Chemistry (FNES)
Craig Rafter
Postgraduate Research Student, Engineering Sciences (FEE)
Hossam Ragheb
Postgraduate Research Student, Engineering Sciences (FEE)
Sonya Ridden
Postgraduate Research Student, Mathematics (FSHS)
Álvaro Ruiz-Serrano
Postgraduate Research Student, Chemistry (FNES)
Melissa Saeland
Postgraduate Research Student, National Oceanography Centre (FNES)
Kieran Selvon
Postgraduate Research Student, Engineering Sciences (FEE)
Ashley Setter
Postgraduate Research Student, Engineering Sciences (FEE)
Alejandra Vergara Lope
Postgraduate Research Student, Engineering Sciences (FEE)
Jonathon Waters
Postgraduate Research Student, Engineering Sciences (FEE)
Thorsten Wittemeier
Postgraduate Research Student, Engineering Sciences (FEE)
Chris Wood
Postgraduate Research Student, Ocean & Earth Science (FNES)
Emanuele Zappia
Postgraduate Research Student, Engineering Sciences (FEE)
Davide Zilli
Postgraduate Research Student, Electronics and Computer Science (FPAS)
Elisabeth zu-Erbach-Schoenberg
Postgraduate Research Student, Management (FBL)
Matthew Higgins
Undergraduate Research Student, Biological Sciences (FNES)
Shaun Maguire
Undergraduate Research Student, Biological Sciences (FNES)
Elena Vataga
Technical Staff, iSolutions
Petrina Butler
Administrative Staff, Research and Innovation Services
Susanne Ufermann Fangohr
Administrative Staff, Civil Engineering & the Environment (FEE)
Ella Marley-Zagar
Enterprise staff, Medicine (FM)
William Anderson
Alumnus, Biological Sciences (FNES)
Amy Dean
Alumnus, former UG, Biological Sciences
Richard Edwards
Alumnus, University of New South Wales, Australia
Ben Ient
Alumnus, Biological Sciences (FNES)
Kieren Lythgow
Alumnus, Health Protection Agency
Dan Mason
Alumnus, University of Southampton
Mihails Milehins
Alumnus, University of Southampton
Lloyd Mushambadzi
Alumnus, former UG, Biological Sciences
Nicolas Palopoli
Alumnus, Biological Sciences (FNES)
Oliver Parson
Alumnus, Electronics and Computer Science (FPAS)
Barbara Sander
Alumnus, Chemistry (FNES)
Shanthi Nagarajan
External Member, Korea Institute of Science and Technology
Nils Berglund
None, None
Stephen Green
None, None
Thomas Piggot
None, None
Roshan Sood
None, None
William Tapper
None, None
Christopher Woelk
None, None