What is Whole Genome Sequencing?
Whole genome sequencing (WGS) is the process of sequencing an individual’s entire genetic code, including non-coding regions, to identify any variants or genomic structures across their entire genome. WGS is considered the most comprehensive genetic test available and can detect single nucleotide variants, small insertions/deletions, copy number changes and large structural variants among others.
WGS technology enables the identification of mutations responsible for various diseases and conditions, while also providing insight into their mechanisms and impact on patient health. Furthermore, this technique can also be used to analyze tumor mutation profiles to develop personalized treatment plans tailored specifically for each patient.
WGS can be carried out using various approaches. One way is to conduct whole genome sequencing on an individual and then search for mutations in each protein-coding gene; this technique is known as whole exome sequencing and it allows us to detect mutations that could potentially cause disease.
WGS can also be performed using targeted sequencing, which involves breaking up the genome into smaller sections known as chromosomes and then sequencing each section individually. This approach has proven highly successful at identifying disease-causing mutations.
However, these methods can be both expensive and time consuming; luckily, modern genomic technologies are making WGS more cost-effective and simpler to perform.
Current world genome sequencing techniques (WGS, or next-generation sequencing; NGS) is becoming the preferred way to undertake WGS. NGS involves the simultaneous sequencing of millions of DNA fragments on an array chip; this enables much quicker and more accurate results than prior techniques.
NGS allows NGS users to utilize whole genome sequencing (WGS) on both prokaryotic and eukaryotic genomes. This ability opens up numerous applications of WGS in areas such as pathogen detection and environmental monitoring, as well as oncology – it can detect mutations in circulating tumor DNA (ctDNA) found in patient plasma samples; this helps identify subclones as well as determine which treatments will provide maximum benefit to each individual patient.
How Does Whole Genome Sequencing Work?
WGS (Whole Genome Sequencing) is a laboratory process that uses computerized sequencing of all or most of an individual’s DNA. It is commonly used in research to identify genetic causes for rare diseases, characterize cancer development pathways and detect mutational signatures associated with specific types of diseases. WGS can also be used to sequence the genomes of bacteria, viruses, fungi and other microbes so as to gain greater insight into them and how their populations evolve over time.
To analyze a human genome, DNA samples taken from blood or other sources must first be placed into a sequencing machine which reads each nucleotide to create an individual genome sequence and compare it with that of the reference genome in order to identify regions that differ and may be associated with disease; such differences are known as variants and may be responsible for Mendelian as well as complex diseases.
Once identified, variants are prioritized based on their predicted impact on health, and a report is prepared for review by physicians. With so many potential variants that can be identified across genetic disorders and conditions, laboratories must take special care when interpreting results, even if the outcome is non-actionable; this ensures that appropriate patients receive appropriate treatments.
As technology for whole genome sequencing advances and costs decrease, more physicians are opting to offer this test to their patients. Whole genome sequencing often provides accurate and comprehensive diagnosis of genetic disorders that is unavailable via other tests such as gene panels or clinical exome sequencing.
WGS provides information about many genes; however, genetic disorders typically are caused by only a select few of these. When offering WGS for clinical diagnostic purposes, laboratories often utilize a virtual panel approach in their tests that involves only analysing known associations to a disorder – this increases risk for incidental findings over more targeted testing strategies.
What are the Benefits of Whole Genome Sequencing?
Genome sequencing is an invaluable diagnostic tool used by research to pinpoint Mendelian and complex diseases’ genetic origins and reveal their complex interactions between genes, proteins, and cellular processes for greater insight into our understanding of human anatomy.
By virtue of falling sequencing costs in recent years, whole genome sequences are now readily accessible to medical professionals for clinical use. Their benefits include diagnosing inherited diseases, providing genetic counseling and testing to relatives, and aiding with developing personalized treatments for individual patients.
Whole Genome Sequencing offers many advantages when diagnosing disease. Not only can WGS pinpoint specific mutations that contribute to certain illnesses, but it can also detect variants not detected by traditional molecular genetic tests like WES and targeted sequencing.
Genome sequencing can often bring shocking news for families. If an infant is diagnosed with hemochromatosis, for instance, their parents will face difficult decisions that require genomic sequencing. But overall, genomic sequencing could save lives by helping families plan ahead and take preventive steps against any future diseases that might emerge – potentially saving lives in the form of lifesaving preventative measures before any health complications develop.
Whole genome sequencing provides another significant benefit by its ability to detect copy number variations (CNVs). While existing technologies, like array comparative genomic hybridization (aCGH), can only detect large deletions and duplications, genome sequencing accurately reports all classes of CNVs that exist within an individual’s genome.
Whole genome sequencing can also be used to identify cancer drivers and predict response to treatment, making this approach especially helpful in identifying high-risk patients who might otherwise face unnecessary surgery or chemotherapy treatment.
WGS has also enabled researchers to discover new genetic diseases, such as an extremely rare form of leukemia. Such discoveries would not have been possible without advances in genomic technologies and whole genome sequence data being made readily available.
Though whole genome sequencing (WGS) can be an extremely valuable diagnostic tool, its main use in clinical applications is limited to screening for certain disorders. Therefore, results of WGS tests will only indicate whether someone has one of these genetic diseases if their genes have been associated with said disorder.
What is the Cost of Whole Genome Sequencing?
Long considered prohibitively expensive for widespread clinical implementation, genome sequencing costs have long been seen as one of the main impediments to implementation of this technology. Whole genome sequencing provides the most thorough method to analyze genetics and can shed light on one’s risk for diseases like cancer, heart disease and autoimmune conditions.
For the initial human genome sequence, it cost $3 billion and took several international institutes and hundreds of researchers 13 years. Since then, however, technological advances have made genome sequencing much less expensive; by 2010 high-throughput next generation sequencing could be done for $100,000 per genome – this amount should decrease even further as advances from companies like Illumina, BGI and PacBio enable this price point to decrease to $200 by 2024.
WGS technology’s low costs have opened the way to medical applications that would not have been possible or cost-effective with older technologies, such as archived and analyzed WGS data for an individual patient over their lifespan, saving both time and money on repeated tests while providing invaluable medical insights.
CDC scientists can use WGS technology to quickly and accurately gather results that help prevent the spread of infectious disease and improve public health outcomes, such as pinpointing foodborne illness outbreaks by identifying genes responsible for resistance.
As genomics evolves, one chart has become ubiquitous within industry slide decks: that from the National Human Genome Research Institute displaying how genome sequencing costs decreased dramatically between 2001 and 2022 – due in large part to technological advancements like modern high-throughput sequencing methods which have proven superior to Sanger sequencing methods.
Given the exponential expansion of computing power, Moore’s Law seems to be holding true when applied to sequencing costs as well. He predicts that every two years the number of transistors on microprocessors doubles; similarly it seems true for sequencing costs as well.
