Whole genome sequencing means sequencing the total genetic content in the sample of interest. Sequencing all the genetic information has numerous advantages over targeted gene sequencing (like 16S rRNA) for a metagenomics study.
Although both methods would illustrate which organisms resides at what proportion in a sample, whole genome sequencing provides more information than the relative abundance of organisms in a sample.
Capturing all the genomic variation in samples would allow disentangling organisms at a strain-level resolution, as well as capturing academically and clinically relevant functional variants, such antimicrobial resistance and virulence variants. With whole genome sequencing data, it is possible to analyze taxonomic, functional, and clinic difference between samples at once.
The Advantages of Whole Genome Sequencing
Can provide vital information on genetic variants
All living things diverge in their genome sequences via the genetic variation that they harbour. Even the cells of an organism may diverge in the genetic sequences that they have. Dissipating the genomic variation between living, as bacteria, virus, or fungi proves itself critical in clinical settings where genetic variant information would impact the prescribed antibiotics, as antimicrobial resistant microbes diverge in their genetic variation which grants them resistance to varying antimicrobials.
Moreover, using genomic sequencing to capture all the genomic variation in cells is invaluable for identifying strong signals for polygenic hereditary disease, which is where lots of genes interact on disease outcomes. Differentiating strong signals for hereditary disease in the human genome may yield essential information on disease prognosis and treatment.
Another setting where capturing strong genetic variant signals is critical is oncology. Identifying all genetic variants in tumours would define the treatment using smart medications, surgery, radio and chemotherapy, as well as their regiments.
Highest standard of sequencing available
Whole genome sequencing is the highest standard of sequencing available. It is superior to Sanger sequencing because it is less prone to human error and requires less manpower. With less scientist working and room for error, it more accurately sequences whole genetics sequences that are so long that would require thousands of scientists to Sanger sequence.
Whole genome sequencing is also superior over next generation sequencing, even though their accuracies are similar. Where whole genome sequencing differentiates from next generation sequencing is that whole genome sequencing captures all organisms genetic information in a sample. Whole genome sequencing is also more accurate than long-read sequencing technology which only achieves ~90% accuracy where whole genome sequencing has >99% accuracy.
Analyses the entire genome
Elaborate on the advantages of whole genome sequencing analysing entire DNA whereas genotyping or sequencing a panel of desired genes looks only at chosen fragments of the genome.
Whole genome sequencing doesn’t amplify a specific gene or a specific set of genes. It rather sequences all genomic information available in a sample. As it does not rely on amplification or specific primer sets, this method is less biassed than 16S rRNA sequencing and more targeted than exome sequencing. Whereas exome sequencing uses a capture-based method to target and sequence coding regions of the genome, genome sequencing does not necessitate a capture step and instead offers coverage across the entire genome.
Whole genome sequencing also allows for accurate identification of the organisms down to the species and strain levels along with prediction of their functional capacity based on genes present in the sample, as well as capturing all genetic variation information present in genomes.
Better integration of genomic data and clinical information
In the past years, integrating genomic and clinical data to clinical settings has proven beneficial in numerous ways:
- Identifying antimicrobial resistance and virulence genetic variants in the genomes infectious pathogens for precision treatment,
- Stratifying tumours based on their genomic variants for identifying best treatment methods and regiments,
- Capturing genomic variants in human genome allows predicting an individual’s response to drugs and identifying right drug and dose for the individual.
- Stratifying hereditary disease using individual’s genomic variants to predict disease prognosis and treatment.
Drug prescription and development
The development of sequencing technologies that raised massive amounts of human genomic data has paved the way for fusing pharmacology and genetics. Hence, it gave rise to the study of genomic medicine developments such as pharmacogenetics. Pharmacogenetics allows stratification of populations based on their principal genomic variants that affects their drug response. Therefore, pharmacogenetics allows the precision treatment of disease using vast number genetic variants raised by whole genome sequencing.
Explain why genome sequencing can result in substantial cost saving, especially when measured over the lifespan of an individual. Mention the procedure produces data that can be analyzed and interpreted in perpetuity.
Among its numerous advantages, whole genome sequencing is a cost efficient genetic sequencing technology. Back in 2001, 2800 scientists worked using Sanger sequencing to sequence the human genome, it cost ~100M $. The invent of next-generation sequencing costs drastically reduced the cost of sequencing a human genome to 100-10k $ threshold.
Nonetheless, it was thanks to the invent of third-generation, whole genome sequencing when the cost of sequencing a human genome plummeted down to 1000$ threshold (see figure below). In addition to its low cost compared to other sequencing methods, whole genome sequencing is a further cost efficient method, as it allows the analysis of all the functional genes (including AMR and virulence), microbiome residing with the host and all genetic variants at once without the requirement of other tests.
To sum up, whole genome sequencing is an accurate, cost effective and powerful genetic sequencing technology which allows capturing all the genetic information available in a sample.