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MRC DiMeN Doctoral Training Partnership: Building integrated machine learning and genomic approaches to quantitate bone quality and fracture risk


Project Description

Is this project for you?

This PhD Project would suit a student inspired by the prospect of participating in a truly multidisciplinary team. This project sits at the interface between clinical medicine, computer science, and genomic medicine and is ideal for somebody who wishes to further core skills in mathematics, statistics and computation. The student will develop methods and tools in image analysis and bioinformatics for integrating multiscale and multisource information through machine learning.


What is the problem?

Eighty thousand people sustain a fragility femoral neck fracture every year in the UK. The 1-year mortality following this injury is 20-30%, and 30% of surviving patients fail to return to independent living. Susceptibility to osteoporotic fracture runs strongly in families, but is also lifestyle dependent. Dual energy X-ray absorptiometry (DXA) is the standard method used to estimate fracture risk but yields only modest estimates of risk and does not account for the spatial bone microarchitecture or genetic and lifestyle risk factors.


How can we solve it?

In this project, we will use data from the UK Biobank to create the richest and largest imaging omics chart of bone the UK population. We will link our dedicated in-house platform (www.multi-x.org) and high-throughput computational tool for DXA scan analysis (PMID 31647421, 25222069, 28169450) with our expertise in genetic epidemiology (PMID 30664745, 29559693, 30273415) to better understand bone structure, ageing, and fracture. Using these computerized medical image analysis methods we will exploit texture, shape, contour and contextual information and combine it with genetic information, leading to an unprecedented opportunity to understand health and disease to map out imaging and genetic biomarkers for individuals within the wider population.


How can you help us achieve this?

The student will join an inter-disciplinary and cross-institutional team with the expertise to answer the following questions:

Specifically, the student will apply these computational approaches to understand:
1) How variations in local bone texture in the hip bone (femoral neck) with age and gender associate with subsequent fracture events
2) How established osteoporosis risk factors and genetic variation affect femoral neck bone architecture and fracture risk
3) How established treatments, dietary modification and exercise affect local bone architecture to influence fracture risk


What training will you receive?

We feel passionately about the opportunities that Imaging Genomics will bring to our field of human ageing and want to transfer our enthusiasm to a student who also sees the development opportunities in this area. As well as specific training in machine learning and statistical genetics, you will be immersed in the biology of a common, complex disease. You will gain expertise in all these fields through the inter-institutional nature of this project. You will have the opportunity to participate in the seminar and lecture series available at Sheffield and Leeds to maximize the learning resource available. This will include a period of complex trait genomics training at the Helmholtz Institute in Munich, as well as that received at the home institutions.

See these links for more details of the supervisors and their work:
Prof Mark Wilkinson, Faculty of Medicine & Health, University of Sheffield, https://mellanbycentre.org/mark-wilkinson/
Prof Alejandro Frangi, Faculty of Engineering & Physical Sciences, University of Leeds, https://www.cistib.org/afrangi
Prof Ele Zeggini, Helmholtz Munich, https://www.helmholtz-muenchen.de/itg/index.html


Benefits of being in the DiMeN DTP:

This project is part of the Discovery Medicine North Doctoral Training Partnership (DiMeN DTP), a diverse community of PhD students across the North of England researching the major health problems facing the world today. Our partner institutions (Universities of Leeds, Liverpool, Newcastle and Sheffield) are internationally recognised as centres of research excellence and can offer you access to state-of the-art facilities to deliver high impact research.

We are very proud of our student-centred ethos and committed to supporting you throughout your PhD. As part of the DTP, we offer bespoke training in key skills sought after in early career researchers, as well as opportunities to broaden your career horizons in a range of non-academic sectors.

Being funded by the MRC means you can access additional funding for research placements, international training opportunities or internships in science policy, science communication and beyond. See how our current DiMeN students have benefited from this funding here: http://www.dimen.org.uk/overview/student-profiles/flexible-supplement-awards

Further information on the programme can be found on our website:
http://www.dimen.org.uk/

Funding Notes

Studentships are fully funded by the Medical Research Council (MRC) for 3.5yrs.
Includes:
- Stipend at national UKRI standard rate
- Tuition fees
- Research training and support grant (RTSG)
- Travel allowance

Studentships commence: 1st October 2020.

To qualify, you must be a UK or EU citizen who has been resident in the UK/EU for 3 years prior to commencement. Applicants must have obtained, or be about to obtain, at least a 2.1 honours degree (or equivalent) in a relevant subject. All applications are scored blindly based on merit. Please read additional guidance here: View Website

Good luck!

References

https://ieeexplore.ieee.org/document/8880676

https://www.nature.com/articles/s41588-018-0079-y

https://pubs.rsna.org/doi/10.1148/radiol.14140636

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