Implementing single-cell RNA sequencing in low- and middle-income countries: Towards a more diverse genomic research landscape
Recently, an article was published in the European Journal of Human Genetics which discusses strategies for expanding the availability and utility of single-cell RNA sequencing in low- and middle-income countries (LMIC).
Single-cell resolution RNA sequencing (scRNAseq) has emerged in recent years as an important tool to investigate the impacts of different factors such as genetic variants, drug treatments, and environmental factors on a cellular level. Its application has significant implications for rare disease research, treatment, and care, as it can be applied to better understand traits such as variation in drug responses or individual susceptibility to specific conditions.
While there are logistical and structural challenges to implementing scRNAseq in LMIC, a more immediate barrier must be overcome before they can be addressed: the lack of representation in genomic research. The accepted reference for scientists to use for comparing DNA sequencing results is the Human Genome Reference Sequence (HGRS), developed as part of the Human Genome Project and last revised in 2019.
While this was an international undertaking, regions with a higher proportion of LMIC such as Africa, East Asia, South America, and the Middle East are vastly underrepresented. The HGRS and subsequent large-scale genetic studies have overwhelmingly drawn on individuals of European ancestry, and this lack of diversity creates a significant knowledge gap in the genetic factors which influence various aspects of health on a global scale.
This lack of representation means that even when LMIC are able to overcome infrastructure challenges to implementing scRNAseq and other sequencing technologies, their analysis may not be applicable to their population. This severely limits the extent to which these countries can implement scRNAseq to advance research and care for rare diseases.
In this article, the authors provide a work flow for how ancestrally-diverse single-cell transcriptomic and spatial omics studies can be conducted in LMIC in order to overcome this barrier. They also provide a number of recommendations for actions which can be taken to overcome infrastructural, technical, and ethical challenges to conducting such studies. These include:
- Investment in training and capacity building
- Building local research manufacturing sites
- Utilisation of open-source tools
- Strong security protocols and data management
- Strengthening of ethical and legal frameworks
By addressing these challenges and undertaking genomically diverse research studies, it will be possible to construct high-quality, representative reference atlases which can be used as a foundation for future research, translational studies, and the development of personalised medicine. As such, they will allow for better knowledge and more effective treatments for rare diseases for the inhabitants of LMIC, as well as diverse populations all around the world.
