PhD Study : Integrating whole genome sequencing (WGS), transcriptomics, proteomics, and patient phenotypic data to identify predictive biomakers for rheumatoid arthritis biologic treatments

Summary

Rheumatoid arthritis (RA) is a chronic destructive disease of joints, which affects ~ 25 million adults in the world. As a painful and disabling disease RA presents significant healthcare burden to society. The standard treatment route of RA starts with traditional DMARDs (Disease-modifying anti-rheumatic drugs), such as Methotrexate, to which 30-40% of patients would not respond. Those non-responders will undergo anti-TNFa based biologic treatments, but again 30-40% of them would not respond to TNFa biologics and they are referred to as secondary non-responders. While we conduct related research to identify potential drugs for the secondary non-responders, it would be highly desirable to be able to accurately predict using effective biomarkers which patients are secondary non-responder, in order to triage high cost of biologic drugs.

In this project, we are exploiting gene expression data from public databases,  WGS and proteomics data from our own patient cohort, together with patient demographic and clinical phenotypic data, to develop integrative bioinformatics analysis pipelines with  the aim is to identify high quality genomic biomarkers of secondary non-responder among RA patients.

The overall aim of the project  will be achieved through the following steps:

1)We have identify a number of suitable datasets containing the gene expression profiles of secondary non-responders and responders; differential expression analysis on the transcript level will allows us to identify genes that are strongly associated with biologic drug response.

2)We have conducted proteomics analysis using olink technologies to profile our patient cohort with selected panels of proteins related to immune response, inflammation etc. Bioinformatics analyses of the proteomics data and patients’ secondary response status data will identify candidate proteins that are strongly associated with biologics response.

3)All the patients in our cohort will have their whole genome sequenced as a research collaboration with Genomics Medicine Ireland. This provides a rich source of information on the full genetic makeup of all our patients. We will develop and test robust bioinformatics pipelines for the processing and analysis of WGS data.

4)Integrating the three streams of data as described above and patients drug response data, we will develop and test an integrative bioinformatics approach to identifying highly promising genomic biomarkers that are predictive of RA patients’ response to biologic treatments. The integration of all three types of omics data is essential as it helps to narrow down the search space of WGS, increase confidence, and converge to the most effective genomics biomarkers for biologic drug response.

5)We will perform validations on the predictive biomarkers with an independent public dataset and/or new cohort of RA patients.

This is primarily a Bioinformatics and BigData research project, with data obtained from both public domain and our own centre; it requires an individual with good computational skills and statistical knowledge.  A good understanding of basic biological processes and some experience with basic biological lab experiments would be desirable, but training on these aspects will be provided during the course of PhD study.

Essential criteria

Applicants should hold, or expect to obtain, a First or Upper Second Class Honours Degree in a subject relevant to the proposed area of study.

We may also consider applications from those who hold equivalent qualifications, for example, a Lower Second Class Honours Degree plus a Master’s Degree with Distinction.

In exceptional circumstances, the University may consider a portfolio of evidence from applicants who have appropriate professional experience which is equivalent to the learning outcomes of an Honours degree in lieu of academic qualifications.

• Sound understanding of subject area as evidenced by a comprehensive research proposal
• A comprehensive and articulate personal statement

Desirable Criteria

If the University receives a large number of applicants for the project, the following desirable criteria may be applied to shortlist applicants for interview.

• First Class Honours (1st) Degree
• Completion of Masters at a level equivalent to commendation or distinction at Ulster
• Research project completion within taught Masters degree or MRES
• Experience using research methods or other approaches relevant to the subject domain
• Work experience relevant to the proposed project
• Publications - peer-reviewed
• Experience of presentation of research findings

Funding and eligibility

The University offers the following levels of support:

Vice Chancellors Research Studentship (VCRS)

The following scholarship options are available to applicants worldwide:

• Full Award: (full-time tuition fees + £19,000 (tbc))
• Part Award: (full-time tuition fees + £9,500)
• Fees Only Award: (full-time tuition fees)

These scholarships will cover full-time PhD tuition fees for three years (subject to satisfactory academic performance) and will provide a £900 per annum research training support grant (RTSG) to help support the PhD researcher.

Applicants who already hold a doctoral degree or who have been registered on a programme of research leading to the award of a doctoral degree on a full-time basis for more than one year (or part-time equivalent) are NOT eligible to apply for an award.

Please note: you will automatically be entered into the competition for the Full Award, unless you state otherwise in your application.

Department for the Economy (DFE)

The scholarship will cover tuition fees at the Home rate and a maintenance allowance of £19,000 (tbc) per annum for three years (subject to satisfactory academic performance).

This scholarship also comes with £900 per annum for three years as a research training support grant (RTSG) allocation to help support the PhD researcher.

• Candidates with pre-settled or settled status under the EU Settlement Scheme, who also satisfy a three year residency requirement in the UK prior to the start of the course for which a Studentship is held MAY receive a Studentship covering fees and maintenance.
• Republic of Ireland (ROI) nationals who satisfy three years’ residency in the UK prior to the start of the course MAY receive a Studentship covering fees and maintenance (ROI nationals don’t need to have pre-settled or settled status under the EU Settlement Scheme to qualify).
• Other non-ROI EU applicants are ‘International’ are not eligible for this source of funding.
• Applicants who already hold a doctoral degree or who have been registered on a programme of research leading to the award of a doctoral degree on a full-time basis for more than one year (or part-time equivalent) are NOT eligible to apply for an award.

Due consideration should be given to financing your studies. Further information on cost of living