Genome Sequencing Comparison
Did you know that you can get your full genome sequenced today? Ten years ago it would have cost over a million dollars but now it is relatively affordable. However, there exist several companies offering several options that may be confusing. This blog entry aims to outline and clarify the biggest companies offering this service to the public.
Have you ever heard the terms WGS, WES, DNA Sequencing, 30x, 100x, Nebula Genomics, 23andMe, AncestryDNA, Dante Labs? These terms seem pretty obscure. Lucky for you, in today’s post, I will be breaking down all these terms so you can understand the 101 of DNA Sequencing. After reading this, you should be able to understand the different types of DNA tests, as well as what type of DNA test you should purchase based on your needs.
The Basics of DNA Sequencing
First of all, what does 30x vs 100x even mean? The number before the "x" is the coverage, meaning the average number of times your genome will be sequenced. For example, 30x WGS means that your entire genome will be sequenced an average of 30 times. Why is this important, you may ask? The more times a genome is sequenced, the greater statistical power it has, making it easier to determine if results are a sequencing error or if they are a true mutation of the gene. In layman terms, this means that 100x has precision and reliability than 30x. However, based on the type of sequencing you decide to do, 100x may not be necessary.
There are four types of DNA sequencing that you may decide to do: Whole Genome Sequencing (WGS), Whole Exome Sequencing (WES), RNA Sequencing, and ChIP-Sequencing. The most common types of sequencing are WGS and WES, which we will be discussing today.
Whole-exome sequencing (WES) is a type of targeted sequencing to detect exonic variants. Exonic variants result in a single nucleotide change in the DNA that could produce a mutation of an Amino Acid (the substance that determines what proteins get produced in the body). Studying amino acid mutations allows an individual to explore if there are any problems with missing/extra proteins that the body does not need, which is often a cause of disease. Instead of studying the entire genome, WES studies the exome, which determines all the possible transcribed proteins that exist within the body. The exome represents less than 2% of the genome but contains approximately 85% of known disease related variants. Exome sequencing is a cost-effective approach when whole-genome sequencing isn't practical or necessary. Using exome sequencing, researchers can also determine what genes most likely affect your phenotype, using this sequencing method. For example, a researcher might be able to determine if you have blue eyes or brown eyes just from your DNA phenotype. As this is a smaller region of the genome, a greater coverage of 100x is typically recommended.
Comparatively, whole genome sequencing (WGS) is a high-resolution view of the entire genome, consisting of all expressed and unexpressed DNA available in an individual. This information is important to identify inherited disorders and mutations, but it is more expensive and time consuming than studying just the exome. This data can be used to track and prevent diseases you may have genetic predispositions to. This method captures both large and small variants that might be missed with targeted approaches of genetic sequencing such as WES. Your WGS tells you every genetic variant you carry, not just common ones. Whole Genome Sequencing is useful for knowing your ancestry, genetic health risks and can be used for other genomic research. WGS is becoming more attractive than WES due to the greater range of data it collects, as well as its decreasing cost with time. The recommended coverage for this type of sequencing is 30x to 50x depending on the technology and statistics used.
Best Companies for DNA Sequencing
Nebula Genomics
Nebula genomics is the best brand for whole genome sequencing according to Lifespan Society of BC, with up to 100x sequencing depth allowing for highly accurate DNA sequencing data. While 23andMe and AncestryDNA read your DNA at only 600,000 positions, Nebula Genomics reads each letter of your DNA at 6,000,000 positions, providing incredibly reliable and accurate results. Additionally, you receive full access to 100% of your data, which other companies like 23andMe and AncestryDNA do not do, only examining less than 0.02% of your entire genome.
Nebula Genomics boasts next-generation sequencing (NGS), which helps sequence many short DNA molecules faster and on a larger scale. This method is more recent and advanced when compared to techniques used by 23andMe and AncestryDNA. The DNA analysed by Nebula also reads your autosomal DNA (sex chromosomes) and mitochondrial DNA. Analyzing these extra genetic markers help to fully reveal your whole DNA makeup.
Currently, Nebula has three packages for whole genome sequencing. The basic package ($99 USD) provides 0.4x coverage, the deep package ($299 USD) provides 30x coverage, and the ultra deep package ($999 USD) offers 100x coverage. You will also have to pay shipping outside of the USA, after which you will have a 14-day trial of the Nebula Genomics reporting service. After the trial, subscription will be $10+ per month, or $200 for lifetime access to the service. You can also download your data to analyze using other services if you choose to not use the subscription model.
Their subscription model allows access to their research library, as well as Nebula Explorer, which allows you to compare your DNA to scientific literature in order to generate risk scores for certain health conditions. Nebula Explorer includes a genome browser, a gene analysis tool that can analyze any gene, and a variant search tool that shows you which of your genetic variants have been identified and studied in literature. Moreover, information is updated weekly. Nebula Genomics also has additional technologies such as a comprehensive ancestry report, and an oral microbiome report, however the cost of these subscriptions add up.
If you choose to use the subscription model, you can also upload your raw DNA data collected from other service providers, instead of purchasing your WGS through Nebula. This will allow you to see correlations that the original company may have excluded from your results. There are a lot of options and flexibility with Nebula Genomics. However, you can get many of these results from Genomelink and other third-party DNA analysis sites for much cheaper.
Whole genome sequencing is expensive and not as common as other methods of sequencing, so Nebula Genomics' database is not as vast as mainstream companies like 23andMe. As WGS is not mainstream, you will not be able to upload this data to other services and benefit from them, like you can do with data collected from cheaper kits from 23andMe or Ancestry.com. However, Nebula Explorer is a user-driven process which allows you to see all the research that has been done on your genome, including preliminary research that may not be available on mainstream sites like 23andMe.
Additionally, although the amount of data generated by whole genome sequencing is unmatched, the reference data to compare your own DNA is also lacking due to the small number of people conducting WGS. There also isn't that much information to be gained from large parts of your DNA as science hasn't progressed that far yet. The problem with this, however, is that not all Nebula Genomics health data has been approved by the FDA for diagnostic processes. However, having this data for the future can be useful as more research and technologies are generated.
Additionally, Nebula Genomics does provide a great deal of scientific literature for customers to compare their genetic data to, however, this service does not offer users personalized information or recommendations based on their results.
Unlike 23andMe, Nebula Genomics does not use their customer data for research purposes, and stores data using blockchain technology, which is completely anonymous and secure in the event of a data breach. They also allow customers to pay for their services anonymously using cryptocurrency or a prepaid credit/debit-card. Customers can also browse their site using a VPN and ship anonymously to a location of their choice.
If you would like to purchase a whole genome testing kit from Nebula Genomics, Lifespan Society of British Columbia provides a $50 USD discount for members using the code SUMMERSALE. Please note that we have not been endorsed by Nebula Genomics in any way to provide this information for you. All information is factual and unbiased.
Dante Labs
Dante Labs offers whole genome sequencing of DNA samples. Although they previously used to sell microarray tests (same as 23andMe and AncestryDNA) and whole exome sequencing kits, it is unclear if these products are still available. Some sites claim that Dante Labs provides whole genome sequencing at 3 different coverages, as well as a whole genome/whole exome sequencing package. However, I wasn't able to find these options on the website. The only product listed on Dante Labs' website was their whole-genome sequencing package with coverage of 30x, sold at $550 USD. They often have large discounts for this package though, especially during Black Friday sales. Their products are shipped worldwide.
DNA reports can also be purchased by Dante Labs as "panels" for $49 per report. These panels provide information on a specific topic, for example "nutrigenomics" or "cystic fibrosis", so multiple reports have to be purchased. The reports begin with a quick summary of all the variants analyzed in the report. A chart is provided, describing each characteristic/condition and providing a brief summary of how your DNA influences it. For each characteristic included in the report, there is a detailed description including the relevant SNPs, your genotype, and what a particular genotype means to you. Some claim that these reports don't prioritize their information, making it difficult for consumers to know where to start reading the information. Although there is a lot of detail included within these reports, it still seems a bit simplistic for the price-point of $49. The reports aren't holistic or personalized either. It is also unknown if panels get updated on an ongoing basis, or if new reports have to be repurchased.
As of March, 2022, however, Dante announced the initiation of their Extensa platform which is similar to Nebula Explorer. This platform includes enhanced reports with monthly updates, a comprehensive suite of panels available for WGM, and an additional report delivered to customers each month for free. It is unclear if this is available to the public yet though. However, with more options at lower costs, Nebula products do seem like a better deal for their value.
The sequencing of data by Dante Labs is a bit more limiting compared to Nebula Genomics, as they do not sequence mitochondrial DNA, analysis of immune system genes, or a specialized form of CYP2D6 gene analysis that is helpful for medication and drug reaction analysis. Furthermore, their data is stored on an Amazon cloud (Amazon Web Services). Amazon also analyses the raw sequencing data for Dante Labs, using a bioinformatics software owned by Illumina. Some users complain that their files are not able to be deleted though, despite requesting the company to delete them. Contrastingly, Nebula Genomics analyses all their data in-house, anonymously.
DNA data is provided with the purchase of a WGS kit in the form of raw files. However, only VCF files of your whole genome sequence can be downloaded with the DNA kit for free. Customers have to maintain an active subscription with Dante Labs to download FASTQ and BAM files, which are the most important genome data files to have access to.
A major problem with this company however is their lack of customer service, with a 2.6/5 rating on TrustPilot and several customer complaints against the company. Many of these complaints are about customer-service issues or turnaround time. Many customers have reported waiting more than 6 months for their genome, despite Dante's 8 week guarantee. However, a similar delay in turnaround time also occurs with Nebula Genomics so take these reviews with a grain of salt.
23andme
23andme is one of the leading companies for DNA tests for ancestry and health. Although this company does not sequence the whole genome, their DNA test kits utilise genotyping methods to offer information about your health and ancestry at a much lower price than whole genome sequencing. Genotyping is a method of determining the DNA sequence (genotype) at specific parts of the genome, rather than measuring the whole genome itself. As a result, these tests only decode 0.02% of your DNA.
23andme provides 3 DNA test kits on their website: their Ancestry + Traits Kit ($99), Health + Ancestry Kit ($199), and their 23andMe+ Membership ($29/year).
The Ancestry + Traits kit includes 80+ personalized reports of ancestry composition, ancient origin based on mitochondrial and Y chromosome DNA, and Neandrathal ancestry report; as well as a DNA relative finder to identify members of your family tree, and a traits report including genetic traits such as physical features, food preferences, musical pitch ability etc.
The Health + Ancestry kit includes all the information in the Ancestry + Traits Kit, as well as information on health predispositions, a wellness report about how their genetics impacts their lifestyle, their carrier status for genetic variants.
The 23andMe+ Membership can be purchased at $29/year with the Health + Ancestry kit at a discounted price of $198. This membership includes access to 10+ exclusive genetic reports and new features as they become available. Some of these reports include information on pharmacogenetics, Heart health, and enhanced ancestry. However, some customers believe that these features should be included in the original kits instead of being an additional membership.
The 23andMe privacy policy secures customer data by removing their personal information from the data. Although individual information is not sold to third-party companies, this company does share aggregate information with third parties for other purposes including research and marketing. Hence, customers relinquish their right to their DNA data if they purchase products from 23andMe.
Processing time takes only 3-5 weeks compared to whole genome testing, and they often have sales of up to 50% off for their products (especially on Black Friday).
Being one of the most famous and mainstream DNA tests in the world, 23andMe boasts a huge database which would provide the most up-to-date information when comparing your DNA to others in the general public. Additionally, 23andMe's health reports focus on DNA mutations observed more frequently in some ethnicities over others, hence some ethnicities would benefit greater than others.
Also, 23andMe's reports are manually curated by their own team of scientists and medical professionals who analyze published evidence, as well as public databases. This ensures that their information is highly reliable and accurate. Additionally, unlike Nebula Genomics, 23andMe is the only at-home genetic test with FDA approval. Hence, it can be used as a preliminary test for some health conditions before seeking clinical help. Having said that, this is NOT a clinical test, so your results should not be a diagnosis of your health concerns without a physician's consultation. As this analyses only 0.02% of DNA, 23andMe cannot be considered seriously for critical genetic predispositions requiring screening for medical reasons.
If this is your first DNA test and you are looking for an easy one-stop test, then 23andMe might be the right choice if you don't care about the privacy issues. 23andMe seems to be good for individuals who want to learn more about their genetic information for entertainment purposes or curiosity, but it does not contain nearly enough information to give a comprehensive report of an individual's entire genomics composition. AncestryDNA might be a better option if you are interested in your ancestry, or whole genomic sequencing might be preferred if you are interested in more detailed health data. 23andme only sequences a small amount of data, and uses the rest for their own research. Despite the cheaper price point, some individuals might prefer whole genome sequencing for a more detailed analysis.
AncestryDNA
AncestryDNA is a DNA test service that analyzes and gives information about your family tree, using genotyping. They have also introduced a new test called AncestryHealth, which looks at genetic risks and carrier status. This company has one of the largest databases of DNA samples worldwide, having a greater database than 23andMe. This makes it possible to connect with more living cousins. If you are specifically looking at family trees and genetic relatives, AncestryDNA is the way to go.
AncestryDNA charges $99 for their ancestry kit, including the price for two-way shipping. However, AncestryDNA requires a monthly subscription to continue accessing your data and reporting features, which increases the overall price significantly. But if you cancel your subscription, you can download your raw data and take it with you.
AncestryDNA provides comprehensive results on ancestry. This includes information about ethnicity estimates of populations you are most related to, pie chart containing your biggest matches, and detailed ancestry matching with over 1000 regions. A timeline of historical changes related to your DNA curated by an expert team of historians is also available. AncestryDNA also covers potential migration paths your family may have taken, family connections to your potential relatives on the platform through DNA matching, and non-medical traits like eye-color, cilantro aversion and birth weight.
AncestryDNA has recently added more ethnicity populations and broken down larger regions into smaller more precise ones. It also continually searches for matches as its database grows. On the other hand, 23andME only looks for DNA matches through an opt-in program. AncestryDNA also provides access to their historical records database through an additional subscription, which will allow you to build a family tree from the ground up.
However, the ancestry results are only provided through an autosomal test, not including information about your direct paternal and maternal haplogroups. This means your data does not look at mtDNA, which would give information about your most common ancestor on either side of the family. Information about haplogroups might not be necessary unless users have a specific need, as AncestryDNA is comprehensive in itself.
Additional results from your ancestry DNA include information on your genetic health, carrier status and wellness traits, cancer risks, connective tissue disorders, heart and blood health, and wellness traits. If you require more information about your health, you could purchase the AncestryHealth package.
AncestryHealth is a newly introduced, separate kit costing $179 for new users, and $99 for existing users. AncestryDNA's new partnership with PWNHealth will also give you access to genetic counselors. You can't take this test if you have given or received a bone marrow or stem cell transplant. This test however misses a lot of health conditions reported by other companies, so it should not be considered a diagnostic test. Companies like 23andMe offer more diverse health traits, but their ancestry results are not as robust as AncestryDNA.
Similar to 23andMe, AncestryDNA keeps your information private with no identifying features in their database. You are also able to delete your DNA data by notifying the company. However, the same problems arise with privacy as 23andMe, where de-identified, aggregated genetic information is sold by AncestryDNA. This information is up for sale to the highest bidder.
Bottom Line
DNA testing can provide critical information about your ancestry and your health.
Whole genome sequencing provided by Nebula Genomics and Dante Labs provide comprehensive information about your entire DNA sequence, which is perfect for people who want information about specific aspects of their DNA, those who have expert knowledge to sieve through their DNA information, and those who have the resources to afford these packages. Although Nebula Genomics provides more features, information and accessibility, Dante Labs might be better for those situated in Europe (where they operate from).
If you are a newbie with DNA testing, 23andMe and AncestryDNA are both great options. Due to their large database and more detailed information, AncestryDNA is recommended if you want information about your ancestry. However, if you want a broader range of information including health, traits and ancestry, then 23andMe might be a better spend.
Despite their advantages and disadvantages, all four companies provide important valuable DNA information. It ultimately depends on your individual choice and your needs.
Remember: if you purchase products from Nebula Genomics, Lifespan Society of BC offers our members $50 off using the code SUMMERSALE.
