How do I choose between whole genome sequencing and whole exome sequencing?

Whole-genome sequencing (WGS) and whole-exome sequencing (WES) are two primary methods for exploring genetic variations. Each technique has its own distinct benefits and limitations. The choice between these techniques depends on the specific goals, cost, and the nature of the study.

Whole-Exome Sequencing (WES) targets only the exonic regions, which constitute only a small portion of the entire genome but harbor more than 80% of known disease-causing mutations.

• Advantages of WES: WES costs less than WGS due to reduced sequencing and data storage needs. It produces considerably smaller datasets, resulting in faster and simpler data analysis. WES also offers higher sequencing depth, which is more effective when extensive coverage of target regions is needed. 
• Limitations of WES: WES provides limited coverage. It misses out on most of the genome and portions of the exome, potentially overlooking significant variations, particularly in non-coding regions. Another limitation is the ability to reanalyze data. 

Whole-Genome Sequencing (WGS) covers the entire genome, including both coding and non-coding regions, offering a comprehensive view of genetic variations.

• Advantages of WGS: WGS captures variations in both coding and non-coding regions, providing a more thorough understanding of genetic factors influencing disease. It also provides more advanced information due to its ability to detect regulatory elements, methylation patterns, and other factors that WES misses, offering deeper insights into gene expression and regulation. Moreover, WGS enables retrospective analysis as new discoveries are made about non-coding regions.
• Limitations of WGS: WGS is more expensive due to the greater amount of sequencing required. In addition, the process generates large datasets, necessitating advanced bioinformatics tools and substantial storage capacity, making the analysis process longer and more complex.

Factors To Consider When Choosing Between WES and WGS

These are two main factors to take into consideration when choosing between WES and WGS.

• Nature of the Study: WES is suitable for studies focusing on known or suspected mutations within coding regions, making it ideal for specific genetic disorders. In contrast, WGS is preferable for exploring unknown causal variants, particularly in rare and undiagnosed genetic diseases, as it offers an unbiased and comprehensive approach.
• Specific Disorders: WGS is better suited for diseases linked to non-coding regions or those associated with repeat expansions and copy number variations. WES, however, remains valuable in clinical settings, especially for diagnosing nervous system disorders, seizures, and dermatological conditions.

Overall, given its advantages and cost-effectiveness, WES is a more practical, efficient, and affordable option for targeted studies. On the other hand, its more comprehensive and future-proof approach, make WGS the preferred choice as technologies evolve and our understanding of the genome deepens.