The completion of The Human Genome Project in 2003 marked a big leap in the development of genomics technology, allowing for more robust and cost-effective methods with reduced turnaround time. Genomics has immense potential in both research and clinical settings. In the research sphere, it can unlock secrets related to unknown genes and their mechanisms, pathways leading to disease or poor prognosis that can then be used for development of new tests and treatments while in terms of clinical use, it can cover everything from diagnosis to treatment of human diseases. This has naturally stirred interest among scientists, clinicians and translational researchers, prompting some to build up the necessary infrastructure in-house while others turn to external service providers. Consequently, many biotechnology companies have been set up to offer such services. At this point it is essential to understand factors to consider while seeking or engaging with providers of such services.
Types of Genomics Services
Ready-to-use kits and protocols are available for laboratories and buyers that have the necessary in-house infrastructure and expertise. These simpler solutions reduce the complexity associated with genomics testing and analysis.
Laboratories and buyers lacking the required infrastructure and expertise can access a wide range of services such as DNA and RNA sequencing; genotyping to detect single nucleotide variant (SNV), single nucleotide polymorphism (SNP) and copy number variations (CNVs) as well as genotyping of targeted regions and whole genome; epigenetics, gene expression and transcriptome analysis. Typically, technologies such as microarrays, quantitative or Real-Time polymerase chain reaction (qPCR or RT-PCR) and next-generation sequencing (NGS) are leveraged to provide genomics services.
Selection of Services
Bearing in mind the pros and cons of the technology used, the selection of service will be primarily guided by the cost and aim of the testing.
For example, when the aim is to identify known sequence variants (typically for small number of target genes and samples), targeted sequencing (for example, exome sequencing) using RT-PCR or microarrays may prove more cost effective.
On the other hand, when the aim is complex, and there is interest to uncover novel variants as well, more costly whole genome sequencing (WGS) can be utilized. WGS using NGS would be more appropriate for sequencing large genomes, such as human genome.
Similarly, to understand complex genetic diseases that are multifactorial (caused by genetic and environmental factors) or do not follow inheritance model, WGS using NGS with or without other omics analysis (for example, transcriptomic, proteomic, or epigenetic analysis) may be inevitable.
It is also noteworthy that, with easy accessibility and reduced cost, NGS is gaining more popularity.
Utilization of Genomics
While genomics has traditionally been applied in research settings, it is increasingly demonstrating its utility in clinical settings.
For example, ready-to-use kits and protocols have facilitated discovery and identification of novel biomarkers associated with diagnosis, prognosis and treatment of human diseases such as pancreatic cancer,1 diabetic macular edema,2 breast cancer,3 colorectal cancer4 and lymphomas,5 to name a few.
In clinical setting, WGS demonstrated accurate genomic profiling with shorter turnaround time for risk stratification6 of patients with acute myeloid leukaemia (AML) or myelodysplastic syndromes (MDS). It was also able to correctly classify the inconclusive results from the standard cytogenetics testing.
In another study, WGS identified 18 new diagnoses which included structural and non-exome sequence variants7 that were not detected with the conventional whole-exome sequencing (WES) suggesting the role of WGS as primary clinical test in a setting of paediatric non-genetic subspecialty clinics.
Rapid WGS demonstrated clinical utility with shorter turnaround time of 13 days compared to 107 days required for standard testing8 in case of rare disease testing for critically ill children.
In case of non‐invasive prenatal testing (NIPT), while WGS using NGS can provide a comprehensive analysis of the whole genome, more cost-effective approaches such as targeted sequencing or SNP detection using microarray analysis can also be deployed. For example, microarray quantitation platform has shown comparable results for detecting common trisomies.9
Although genomics testing is thought be a costly affair, in certain conditions, it has the potential to end the diagnostic odyssey,10 thus facilitating timely management. This in turn eliminates extensive diagnostic work up and inefficient management that contribute to overall cost saving.
Things to Consider When Selecting a Genomics Service Provider
When selecting a genomics service provider, there are a few considerations to consider, especially when end-to-end services are needed. The crucial deciding factors include:
- Availability and actionability
- Cost and affordability of testing
- Accreditations and Certifications
- Timelines/turnaround time
- Infrastructure, expertise, and experience
- Bioinformatics analysis
- Report reading, assessment and interpretation
- Reliability of the results
- Insurance providers in-network
- Data protection, storage, handling of left over sample
- Publication ready, compatible graphics/output including raw data
- Customizable services and support
Despite the increasing popularity of genomics testing, one should be mindful of the inherent limitations associated with the technologies used in genomics testing and analysis. For example, NGS has high error rates11;RNA sequencing12 may get influenced by factors such as GC content, read depth and secondary structure.
Furthermore, although genomics is growing in its applications, many gaps remain when it comes to the necessary knowledge, experience and qualifications needed at points of the process like report analysis and its implications. Nevertheless, these limitations are expected to be addressed as people make use of genomic testing more, together with more collaborations between service providers and buyers. This is likely to offer further information on the clinical effectiveness of such tests.
The Bottom Line
Genomics has the potential to contribute to and improve human health, and is expected to be a crucial tool in the near future with its increasing use and accumulation of evidence of its effectiveness.