Introduction
In the 21st century, the field of medical research is on the brink of a revolutionary breakthrough, thanks to the advent of next-generation sequencing technology. Rare diseases, which have long been a challenging area for scientific discovery and therapeutic intervention, stand to benefit significantly from these advancements. A scoping review protocol, as published in BMJ Open (DOI: 10.1136/bmjopen-2018-026278), elucidates the potential of leveraging multi-omic analysis to unravel the complexities of rare diseases.
Main Article
A team of researchers at the Centre for Public Health, Queen’s University Belfast, spearheaded by Katie Kerr, Helen McAneney, and Amy Jayne McKnight, have proposed an ambitious protocol for a scoping review aimed at evaluating the primary research conducted thus far on multi-omics and rare diseases. Funded in part by the Medical Research Council United Kingdom, their comprehensive approach is published under an open-access license and is intended to serve as a launching pad for future explorations in this domain (Kerr, McAneney, & McKnight, 2019).
Rare diseases, despite their individual rarity, collectively affect millions worldwide. They represent a substantial unmet medical need, primarily due to diagnostic hurdles and the scarcity of targeted treatments. The European Commission reported that rare diseases are a major healthcare challenge that requires innovative research solutions (“RARE DISEASES – A major unmet medical need”, 2017). This need for innovation is where multi-omics enters the scene.
Multi-omics is an integrative approach combining analysis from various biological disciplines, including genomics, proteomics, transcriptomics, epigenomics, and metabolomics. By analyzing multiple ‘omics’ layers, scientists can gain a holistic view of the biological networks and pathways underlying rare conditions.
The scoping review protocol adheres to the stringent methodology outlined by the Joanna Briggs Institute, ensuring a systematic and comprehensive examination of the literature. The databases that will be scoured include, but are not limited to, MEDLINE, EMBASE, PubMed, Web of Science, Scopus, and Google Scholar (Joanna Briggs Institute Reviewers’ Manual: 2015). Their review will capture the primary studies involving ‘multi-omics’ and ‘rare disease’, published prior to their specified cutoff date.
Prior research has laid the foundation to appreciate the potential of multi-omics. For instance, studies have demonstrated the value of integrating DNA methylation profiles with gene expression data to unveil aberrant epigenetic patterns in diseases such as IgA nephropathy and ADPKD (Sallustio et al., 2016; Woo et al., 2014). Comprehensive DNA methylation analysis has also clarified the epigenetic landscape in conditions like Fuchs endothelial corneal dystrophy (Khuc et al., 2017) and provided insights into gene regulation in photoreceptor cell death (Farinelli et al., 2014).
Similarly, RNA sequencing (RNA-Seq) has enhanced the understanding of retinal biology and disease, promising to aid in identifying novel therapeutic targets (Farkas et al., 2015). By weaving together RNA-Seq with other omics data, researchers can better understand disease mechanisms.
Aside from disease-specific studies, multi-omics has also illustrated a general potential to dissect complex molecular interactions in conditions like dermatomyositis/polymyositis (Gao et al., 2017) and has given rise to new perspectives on liver cancer (Lin et al., 2016). These studies underline the versatility of multi-omics in addressing diverse pathologies.
Advances in multi-omics align well with the growing push for personalized medicine. In rare diseases, where patient populations are small and heterogeneous, personalized treatment approaches based on multi-omic data could greatly improve patient outcomes. A multi-scale view of inborn errors of metabolism exemplifies the transition from discovery to translation in the context of these technologies (Argmann et al., 2016).
Implementation of robust reporting standards, such as the STrengthening the REporting of Genetic Association Studies (STREGA)-an extension of the STROBE statement, bolsters the quality and reliability of genetic association research in multi-omics studies (Little et al., 2009). Moreover, the use of guidelines such as PRISMA (Preferred Reporting Items for Systematic reviews and Meta-Analyses) for scoping reviews (PRISMA-ScR) ensures transparency and coherence in review methodology and reporting (Tricco et al., 2018).
The researchers anticipate that their scoping review will expose gaps in the existing body of rare disease research and serve as a clarion call for novel investigations. The intent is not merely academic but is designed for practical applications; the findings will be disseminated through peer-reviewed journal submissions and presentations at relevant conferences, augmenting the dialogue surrounding rare disease research and molecular strategies.
Keywords
1. Multi-omics in Rare Diseases
2. Next Generation Sequencing Rare Diseases
3. Omics Analysis Biomarkers
4. Rare Disease Genomic Research
5. Epigenomics and Rare Conditions
Conclusion
The Queen’s University Belfast research team’s commitment to comprehensively scope the landscape of multi-omic applications in rare diseases embodies the adage of where there is research, there is hope. As we stand poised at the cusp of an omics-driven revolution in rare disease diagnosis and treatment, this scoping review will illuminate paths to discover and translate new biological insights directly to patient care. Though the journey is arduous, the potential rewards — personalized therapies that could alter the lives of those suffering from rare diseases — are vast. Annotated by a golden strand of data, the future for rare diseases is increasingly optimistic, as genomic sciences converge on solutions that seemed like distant dreams only a decade ago.
References
1. Kerr, K.K., McAneney, H., & McKnight, A.J. (2019). Protocol for a scoping review of multi-omic analysis for rare diseases. BMJ Open, 9(5), e026278. doi: 10.1136/bmjopen-2018-026278
2. RARE DISEASES – A major unmet medical need. Luxembourg: European Commission, 2017.
3. Sallustio, F., Serino, G., Cox, S.N., et al. (2016). Aberrantly methylated DNA regions lead to low activation of CD4+ T-cells in IgA nephropathy. Clin Sci, 130(10), 733–46. doi: 10.1042/CS20150711
4. Little, J., Higgins, J.P., Ioannidis, J.P., et al. (2009). STrengthening the REporting of Genetic Association Studies (STREGA)-an extension of the STROBE statement. Genet Epidemiol, 33(7), 581–98. doi: 10.1002/gepi.20410
5. Tricco, A.C., Lillie, E., Zarin, W., et al. (2018). PRISMA Extension for Scoping Reviews (PRISMA-ScR): checklist and explanation. Ann Intern Med, 169(7), 467–73. doi: 10.7326/M18-0850