Development of a framework for multiomic analysis in disease research

Student thesis: Doctoral ThesisDoctor of Philosophy


Multi-omics is the combination of several -omic terms to develop an interconnected understanding of molecular biology, which can provide increased insights into disease. Commonly known –omic terms include genomics, epigenomics, transcriptomics, proteomics and metabolomics. The potentials of multi-omic disease research is particularly promising for patients with rare diseases, which affect one in 17 people in the United Kingdom and have a genetic component in ~80% of individuals. Comprehensive reviews of rare disease omics literature identified that multi-omics may offer improved diagnostic yields, increased understanding of pathogenesis and identify therapeutic targets. As part of the 100,000 Genomes Project (100KGP) and in collaboration with the Northern Ireland Genomic Medicine Centre (NIGMC), 815 PAXgene (for RNA analysis) and 738 buffy coats (for DNA and epigenetic analysis) were collected and stored, with the intention of further multi-omic analysis where whole genome sequencing by the 100KGP was insufficient to provide a diagnosis for patients with rare diseases. During the waiting period for return of results from the 100KGP, integrated epigenetic and transcriptomic analysis was conducted in kidney transplant recipients with a variety of rare and common primary renal diagnoses (n = 52) compared to controls with no evidence of kidney disease (n = 28), identifying novel (TTC21B and PLEKHA1) and previously known markers of kidney disease (UMOD, EGF). Following the return of results from the 100KGP, the NIGMC variant interpretation process was evaluated and genetic analysis was conducted of tier 3 variants, in this instance focusing on renal phenotypes. Several tier 3 variants of interest were identified for further follow up in a postdoctoral research project following completion of this PhD (including UROD, VDR, COL18A1, MST1, SCNN1B, BBS9, UMOD and MYH10). Qualitative analysis of perspectives surrounding multi-omics with participants of the 100KGP and carers identified that awareness of these technologies is low, but there is a desire to learn more, and inclusion of the basic concepts of multi-omics within genomics education may be beneficial. Finally, the utilisation of complementary and alternative medicines for management of rare diseases was explored in an online survey and workshop due to high reported usage, and determined there is a need for high quality research supporting safety and efficacy of these treatments. In conclusion, this exploratory, mixed-methodology studentship has highlighted the potentials for multiomics to improve disease research.
Date of AwardJul 2021
Original languageEnglish
Awarding Institution
  • Queen's University Belfast
SponsorsNorthern Ireland Department for the Economy, NI Kidney Research Fund & Science Foundation Ireland
SupervisorAmy Jayne McKnight (Supervisor), Laura Smyth (Supervisor) & Helen McAneney (Supervisor)


  • Rare disease
  • Genomics
  • epigenetics
  • CKD
  • multi-omics

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