We are recruiting

January 25, 2025

PhD position in the SFI Centre for Research Training in Genomics Data Science with Dr. Whysall, Dr. O'Broin, Prof. Seoighe

Background: Rare diseases are characterised by low prevalence: less than 1 in 2,000 people, however together, they are common: there are up to 30 million people living with rare disease in the EU and over 300,000 (6% population) individuals affected in Ireland, a likely underestimated figure1. For most rare diseases, there is no cure and the management of symptoms is often challenging due to persistent lack of knowledge or a failure to translate knowledge into successful therapies1. Moreover, the interpretation of mutations labelled as variants of unknown significance, where the particular point mutation of the gene affected has not been studied in a relevant disease model, means that no meaningful treatments are likely to emerge in future. The wider use of diagnostic sequencing tools has facilitated the identification of novel variants underlying rare disorders.  Once genetic diagnosis is accessed by patients, the patients often wait for several years before appointment with a Clinical Geneticists. Patients seek support/information, patient groups and charities, however these only exist for more common rare disorders. Often patients seek information online to understand the genetic diagnosis. The multitude of tools3-7, are presented in scientific language, and are not always easily findable/accessible for patients. The tools have limited interoperability and do not systematically connect the data across genotypes, phenotypes, drugs and clinical trials nor include whole-cohort information which is critical, as often similar variants may present differently in different patients. These sources do not cover ultra-rare conditions and new variants, increasingly being discovered. The delay in understanding genetic diagnosis, absence of a consistent registry in Ireland, together with lack of information on ultra-rare conditions contribute to significant hardship of those living with a rare disease and reluctance of pharmaceutical companies to carry out clinical trials for novel drugs for rare diseases affecting Irish patients, thus negatively affecting access to new potential therapies.

This project will address an unmet need2 through creating  new data space:  RÉire Net, with integrated genomic, scientific and clinical information on characterised and new variants/diseases and interface with other repositories to empower the patients and healthcare practitioners and stimulate development in the rare disease field. This project will also involve generation of genomic data from undiagnosed patients who have previously undergone exome sequencing and performance comparison of different analytical pipelines for genetic diagnosis.

Specifically, this project will:

- integrate information on known rare disorders based on existing resources to generate scientific and lay summaries.

- synthesise scientific and pathophysiology prediction for new variants in Irish patients  

 - incorporate comparison of different analytical pipelines for genetic diagnosis  from genomic sequence data, novel variants of unknown significance will be functionally characterised

- stimulate research on rare disorders in Ireland through generating a knowledge base on rare disorders, providing knowledge exploration tools and patient connection tools, as well as educational tools and an annual event on rare disease research in collaboration with other institutions in Ireland

- will work with patient representative organisations to provide a source of reliable information and a forum for discussion.

References: 1. An easy guide to rare diseases in Ireland and Consensus for Action, HRCI, IPPOSI and RDI, 2020. 2. Ward et al., Designing rare disease care pathways in the Republic of Ireland: a co‑operative model, 2022. 3. Thompson et al., RD-Connect: An Integrated Platform Connecting Databases, Registries, Biobanks and Clinical Bioinformatics for Rare Disease Research, JGIM 2014 4. Kaldermis et al., InterMine: extensive web services for modern biology; NAR 2014. 5. De Antonio et al., The DM-scope registry, Orphanet J or RD; 2019. 6. Karczewski et al., The mutational constraint spectrum quantified from variation in 141,456 humans; Naure 2020. 7. Firth et al., DECIPHER: Database of Chrmosomal Imbalance and Phenotype in Humans using Ensembl Resources; AmJHumGenet, 2009.

BENEFITS:

•An annual stipend (tax-free) of €18,500

•Fees of €5500/year are provided

•Accommodation is provided while on the 1st semester residential training programme.

•Each student will be provided with a high-end laptop as well as generous travel, workshop, placement and publication cost allowances.

How to Apply:

Email the following as a single PDF file to kasia.whysall@nuigalway.ie

•Cover letter

•CV

•Personal statement (max 600words and it should(1) describe your computational and data analytical skills (2)why you want to study Genomics Data Science and (3) why do you want to pursue a PhD