Computational Modelling Group

NextGen Sequencing

Next Generation Sequencing (NextGen or NGS) covers all the high-throughput nucleotide sequencing technologies and applications that are replacing traditional Sanger sequencing. Applications of NGS include genome/exome sequencing or resequencing, digital transcriptomics, metagenomics and various RNASeq applications. Sequencing capacity is exploding at a rate that far out-strips increases in computational capacity; NGS has shifted the bottleneck for many of these applications from one of data generation to one of data management and processing. This topic is for all CMG members with interests in facilitating, generating or exploiting NGS data.

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For queries about this topic, contact Richard Edwards.

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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.

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.

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.

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.

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.

Imprinting Disorders Finding Out Why

Karen Temple (Investigator)

We are conducting a research project to determine the cause and clinical impact of widespread imprinting aberrations in human development. We are recruiting patients with possible or definite imprinting disorders (due to methylation loss or gain at an imprinted loci)

including Silver Russell syndrome, Transient Neonatal diabetes, Beckwith Wiedemann syndrome, Angelman syndrome Prader Willi syndrome, UPD 14 syndromes and Pseudohypoparathyroidism.

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.

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.

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.

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)
Sarah Ennis
Professor, Medicine (FM)
Hans Fangohr
Professor, Engineering Sciences (FEE)
John Holloway
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)
Stuart Clarke
Senior Lecturer, Medicine (FM)
Robert Ewing
Senior Lecturer, Biological Sciences (FNES)
Christopher Bell
Lecturer, Biological Sciences (FNES)
Jane Gibson
Lecturer, Biological Sciences (FNES)
Ian Hawke
Lecturer, Mathematics (FSHS)
Paul Skipp
Lecturer, Biological Sciences (FNES)
Johanna Jefferies
Research Fellow, Medicine (FM)
Reuben Pengelly
Research Fellow, Medicine (FM)
Gaia Andreoletti
Postgraduate Research Student, Medicine (FM)
Ioannis Begleris
Postgraduate Research Student, Engineering Sciences (FEE)
Michael Breen
Postgraduate Research Student, Medicine (FM)
Rory Brown
Postgraduate Research Student, Civil Engineering & the Environment (FEE)
Paul Chambers
Postgraduate Research Student, Engineering Sciences (FEE)
Caroline Duignan
Postgraduate Research Student, Biological Sciences (FNES)
Robert Entwistle
Postgraduate Research Student, Engineering Sciences (FEE)
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)
Reza J. Forooshani
Postgraduate Research Student, Medicine (FM)
Joseph Jenkins
Postgraduate Research Student, Biological Sciences (FNES)
Andreas Johansson
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)
Gregory Parkes
Postgraduate Research Student, Engineering Sciences (FEE)
Alvaro Perez-Diaz
Postgraduate Research Student, Engineering Sciences (FEE)
Craig Rafter
Postgraduate Research Student, Engineering Sciences (FEE)
Hossam Ragheb
Postgraduate Research Student, Engineering Sciences (FEE)
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)
Emanuele Zappia
Postgraduate Research Student, Engineering Sciences (FEE)
Matthew Higgins
Undergraduate Research Student, Biological Sciences (FNES)
Petrina Butler
Administrative Staff, Research and Innovation Services
Susanne Ufermann Fangohr
Administrative Staff, Civil Engineering & the Environment (FEE)
Richard Edwards
Alumnus, University of New South Wales, Australia
Kieren Lythgow
Alumnus, Health Protection Agency
Mihails Milehins
Alumnus, University of Southampton
Nicolas Palopoli
Alumnus, Biological Sciences (FNES)
Chris Mattocks
External Member, University of Southampton
Stephen Green
None, None
Roshan Sood
None, None
William Tapper
None, None
Christopher Woelk
None, None