Whole-genome sequencing (WGS) is a thorough approach to genome analysis. Tracking disease outbreaks, analyzing the mutations that propel cancer progression, and detecting inherited illnesses have all benefited greatly from genomic knowledge. Whole-genome sequencing has become a potent tool for genomics research due to rapidly declining sequencing prices and the capacity of modern sequencers to generate massive amounts of data.
How Is the Process Done?
The National Health Service uses next-generation sequencing (NGS) technology for whole genome sequencing. The breakdown of the patient’s DNA yields, in a nutshell, the sequencing data for the entire genome. Data analysis can be narrowed down to a subset of genes relevant to the patient’s traits using a virtual panel. All information is preserved which is key for future requirements.
Clinical Uses
- WGS is immensely parallel. Complete genome sequencing includes both protein-coding and regulatory areas. WGS is clinically the most comprehensive genetic testing. There are many variations in numerous genes tested simultaneously.
- Clinical WGS can use virtual gene panels. Though the genome is sequenced, only patient-specific genes are evaluated. Thus, a WGS panel test normally verifies only the genes on the panel, not your patient’s genome.
- WGS is typically employed in rare diseases, but it is now used in cancer patients to analyze the tumor’s (somatic) genome. Potential pathogenic variations in the patient’s constitutional (germline) DNA can be explored. Cancer patients’ testing can reveal somatic driver mutations in tumor genomes that impact treatment eligibility and clinical trials, and mutational signatures that may reveal disease mechanisms or environmental factors.
- WGS is commonly utilized in research to find novel genetic origins of rare diseases or characterize mutational signatures associated with distinct cancers.
- Besides patient samples, WGS can detect and classify pathogenic pathogens like TB and SARS-CoV-2.
Benefits of WGS
- WGS is the most thorough genetic test, which is its main benefit. It can screen many genes simultaneously and detect many variants.
- Single nucleotide variations and minor insertions/deletions are accurately found.
- Uniform genome coverage improves CNV detection compared to full exome sequencing.
- A person’s entire genome is sequenced in WGS. If an initial analysis fails, it may be possible to revisit the original data to evaluate newly identified causative genes.
- WGS can detect protein-coding and non-coding variations.
- WGS can find new genetic disease causes in the study.
Limitations
- Clinical interpretation of the many variations is difficult.
- More variations of unknown significance are generated than with targeted testing.
- Incidental findings are more likely than targeted testing.
- Mosaicism may be undetected due to poor read depth.
- WGS results are slower than other genomic tests.
- The current DNA methylation state is unknown.
Key Pointers
- Whole genome sequencing (WGS) comprises DNA sequencing of the entire genome, including coding and non-coding regions.
- WGS is the most complete genomic test because it sequences most of the genome.
- Numerous genes can be tested at once using WGS.
- A variety of variation types are detected by WGS.
- WGS data is frequently subjected to virtual panels, which implies that not all of the data may be examined.