Complete Human Genome Sequencing — Where Is It Headed?
Flashback to 1989: Rade’s vision was to sequence a complete human genome on one array.Updated to clarify point pertaining to clopidogrel
As chief scientific officer at Complete Genomics, I spend the majority of my time advancing complete human genome sequencing technology and its applications. Genome sequencing has been a passion of mine for almost 25 years, ever since I used my first hybridization-based DNA sequencing assay back in Belgrade, Serbia, in 1987. Even then, I wanted to be able to sequence a complete human genome on a single DNA microarray using microbeads.
At Complete Genomics, we decided to focus on sequencing complete genomes from day one. Partial genomes provide incomplete data that is insufficient for the successful interpretation of most genetic variants, as their meaning is contextually dependent on other variants in the genome. Current exome sequencing technologies, for example, not only miss a significant fraction of exons but also miss all the noncoding variants and structural variations. Also, because of the significant sequencing and computing complexity associated with complete genome sequencing, we realized from day one that as this market develops it will largely be addressed via outsourced service models.
Our current customers range from academic centers and government institutions to biopharmaceutical companies. We enable them to conduct large studies of complete human genomes quickly and cost-effectively.
We are continuing to scale up our commercial sequencing operation. I am particularly proud of the efficiency of our imaging system for our patterned DNB™ nanoarrays that currently use only two pixels per DNA spot and will shortly start using 1 pixel per DNA spot. This is a maximal possible imaging efficiency. Our imaging instrument currently generates one genome per day, and next year will generate several genomes per day. With such efficiency it becomes feasible to sequence millions of human genomes per year for clinical use.
Our sequencing service has already been used to advance medical research in therapeutic areas as diverse as oncology, Alzheimer’s disease and hypercholesterolemia. Despite the extreme complexity of regulatory networks, I expect our understanding of the genetic basis of disease to grow quickly. The number of sequenced genomes is increasing exponentially, and our genomic knowledge grows exponentially with every sequenced genome. A few patients with rare diseases have already been helped, which is just the beginning of a far larger change in medical practice. In the future, patients with diseases that are difficult to diagnose will have their genomes sequenced immediately to help their physicians understand their condition. Furthermore, complete genome sequencing will dramatically improve diagnosis of genetic diseases during routine IVF procedures.
I anticipate that sequencing genomes from cancer biopsies will revolutionize cancer treatment for the several million new patients diagnosed each year. If I am diagnosed with cancer, I will not let my doctor treat it without sequencing my tumor genome first. In the future, I can also see us sequencing cancer genomes as a preventive screening measure. Recent research has shown that a cancer usually takes a decade to develop and starts shedding cells before it produces any symptoms. People could simply get a blood test every two or three years to check for circulating cancer cells. If cancer cells were detected and sequenced, the clinician would have knowledge that would help stop the disease before it develops further.
In the coming years, I foresee routine complete personal genome sequencing as the “universal genetic test”. It is a noninvasive, comprehensive genetic analysis that subsumes all disease-specific genetic tests and produces data that a person can mine throughout their lifetime to improve health. Although clinicians may not be able to interpret all this data now, and we should be careful to avoid overinterpretation, this data will be ready and available when needed, and as our understanding of the genetic basis of disease continually develops in the future. For example, there are genetic variants in the CYP2C19 gene that determine when you are having a heart attack whether you should receive the standard drug clopidogrel or need to receive a different one. That important decision needs to be made within 30 to 40 minutes, which is challenging even for targeted diagnostics. But if you have already had your genome sequenced this information could be available in less than a minute.
This genomic medicine revolution will require lots of technology and software development, additional basic and applied research, and changes to both medical practice and education. I am excited to see it happening.
About This Blog
Dr. Clifford Reid
Chairman, President and CEO
Dr. Reid is a successful, serial entrepreneur. He enjoys commercializing disruptive computing and life sciences technologies.
Dr. Rade Drmanac
Chief Scientific Officer
Dr. Drmanac is a genome sequencing pioneer; his inventions include massively parallel DNA sequencing by hybridization and combinatorial probe ligation. As a group leader at the Argonne National Labs, he was part of the Human Genome Project. In 1993, he cofounded Hyseq, one of the first genomic companies.
Comments:
This is all very fascinating and I'm excited that sequencing whole genomes is becoming easier and cheaper, especially in the context of personalized medicine. I agree, knowing what's hiding in one's genome could prevent or help treat many diseases. However, I am not sure I would want to know that I am at high risk of developing a disease for which there is no treatment. Individuals will need to be protected from their own data if they choose so. Also, insurance agencies might be hacking into genomic data to determine 'preexisting conditions'. These are huge issues that will need to be addressed by our health system before I get my genome sequenced :-)
Posted By: Grazyna on 06/01/2011 at 03:14 PM PDT
Complete Genomics has made 69 samples available so far
http://www.completegenomics.com/sequence-data/download-data/
One in particular named NA18504 is a Yorban African Male carrying 2 copies of APOE4 allele, and as result has ~11x higher risk of developing Alzheimer's Disease.
http://files.promethease.com/reports/genome_NA18504__cgi.html
That's the classic example of something Grazyna might not want to learn. But
http://www.nejm.org/doi/full/10.1056/NEJMoa0809578
suggests that for those who choose to learn, there are net benefits to learning early.
http://www.ncbi.nlm.nih.gov/pubmed/21226570
Further reinforces the harmlessness.
No one wants to force you to have it done. But many of us will need to wait longer than we might like for this chance to better understand part of our bodies.
Posted By: Cariaso on 06/01/2011 at 06:39 PM PDT
There are definitely issues pertaining to the use of human genomic data that need to be addressed. The cost of complete human genome sequencing is decreasing rapidly and it will become a routine medical test much faster than many people imagine.
Posted By: Complete Genomics on 06/06/2011 at 03:41 AM PDT
We are glad that you are finding our genomic repository useful. And we are working hard to reduce the cost of human genome sequencing so that people who would like to get their genome sequenced have the opportunity to do so.
Posted By: Complete Genomics on 06/06/2011 at 03:42 AM PDT
Cariaso, I cannot agree more that accurate, cost-effective genome sequencing is of great importance. Furthermore, as a molecular biologist, I'd love to contribute to the technology because I believe it's going to help millions of patients. I realize that I or someone close might be one of them some day and at that point the possibility of peeking into the genome will be much appreciated. It would also be great to be able to provide affordable whole genome sequencing to those individuals who choose to be informed.
However, extrapolating into the future, mandating genomic testing to every born individual or using it as a screen for an unborn child raises some ethical issues, in my opinion.
Health insurance is another huge concern. Despite some laws prohibiting the institution from discriminating patients based on their health status, it seems as the insurance companies are getting away with a lot of things that seem illegal.
Thank you for the discussion.
Posted By: Grazyna on 06/06/2011 at 09:54 AM PDT
'However, extrapolating into the future, mandating genomic testing to every born individual or using it as a screen for an unborn child raises some ethical issues, in my opinion.'
'Mandating' is hyperbolic speculation. There is absolutely no basis for that concern.
'Health insurance is another huge concern. Despite some laws prohibiting the institution from discriminating patients based on their health status, it seems as the insurance companies are getting away with a lot of things that seem illegal.'
Could you perhaps give one example of 'lots of things that seem illegal'?
I'd like to get back to getting genomic data in the hands of people who want it. You seem to want to stop and have some very long conversations about things that *might* someday happen. But they won't because no one actually wants them. Do you really worry the USA is going to quickly jump from passing GINA, to mandating genetic testing for everyone at birth?
Posted By: cariaso on 06/06/2011 at 02:47 PM PDT
Dear Cariaso,
I respect your opinions; you are entitled to yours and I'm entitled to mine. I'm glad we agree on one thing: fast, cost-effective whole genome sequencing rocks!
To adress your comments...
As great as this country is, it has some flaws...Please Google the pre-existing condition/insurance topic to get countless examples of health or life insurance denial.
I find it important to consider what might happen someday, to think about the good and the bad, to review the pros and cons. Then I feel better about making an informed decision and I am better prepared to deal with the consequences.
I really do hope that you will be able to access your genome shortly. I might be ready for mine in a year or two :-)
All the best!
Posted By: Grazyna on 06/07/2011 at 08:38 PM PDT
I talk about some of these things on my Facebook group
Posted By: Jeff Lester on 06/26/2011 at 10:05 AM PDT
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