NGS Expert Blog

Opinions differ as to whether next generation sequencing is already mature enough to be a useful tool in diagnostic routine.

Below you can find an interview of the cardiologists from the university of Heidelberg about their studies to integrate next generation sequencing into a diagnostic tool. Therefore they do collaborate with Siemens to receive best possible results that can be used by the doctors in the same way as current reports from other technologies.

Scientists estimate that the cells of our bodies are outnumbered 10 to 1 by bacterial cells which live in or on our body.  A previous blog has already pointed out the impact of this fact on sequencing the corresponding host genomes. On the other hand, microbiomes have the potential to play an important role as diagnostic markers, or opening up new ways of treating diseases, such as personalized medicine.

However, we are just beginning to understand the complex relationships of this “social network”, as the Scientific American has called it. The most complex bacterial community within the human body resides inside the gut. In order to obtain a deeper understanding of the bacterial communities of the human gut, there have been several attempts of sequencing the gut microbiomes of larger groups of individuals, such as projects by Arumugam et al., Yatsunenko et al or Schloissnig et al. However, so far, the number of individuals which were analyzed was relatively small (up to several hundreds).

A group of US scientists have now started the “American Gut Project“.  As reported by Genome Web News, this project is planned as a crowd-sourcing study of 10.000 or more individuals in the US. Since this study is part of the “American Food Project”, it will mainly focus on gut microbiome patterns in relation to diet, age and lifestyle. People who would like to participate in this study need to sign up via a website and donate $99. This money will be used to cover a significant part of the cost of the study. In return, participants will receive a taxonomic profile of their gut microbiome.

The analysis itself will be based on 16S sequencing. For part of the samples, additional analyses such as sequencing the complete metagenomes and long term surveys are planned. No doubt, this study will clearly provide us with a huge data set. However, this data set will be highly complex. Also, it still needs to be brought in context with data from other projects.  To my opinion, interpretation of the data still remains the hardest part. Or, as project organizer Jeff Leach has put it in an interview with Genome Web Daily News: “We don’t expect to be able to address some questions, but because of the size of the sample and because of the broad patterns we expect to see in diet and lifestyle, we think some stuff will fall out.”

At the end of August, Mr. Hosono, the Japanese minister for the environment, announced, that the ministry aims to perform whole genome sequencing (WGS) of people who live around the disabled “Fukushima Daiichi Nuclear Power Station”. He said that the WGS project will not be able to relieve concerns immediately, but it will make an important provision for the future. According to Mr. Hosono the main target group for WGS will be children.

These genomic analyses face many problems including the aspect of experiments with humans, maintaining confidentiality, discovery of information according to need, and others. This story reminds me once more that NGS technologies start to have social impacts.

Six floors for Next Generation Sequencing in the middle of Manhatten – this is going to be exiting. Listen to the interview from Bio-IT World with Nancy Kelly, founding executive director of the New York Genome Center.

Is sequencing your personal genome a curse or a blessing? A recent radio broadcast from NPR news summarises two scientist’s opinions and their practical experiences with genome sequencing  (listen to the radio broadcast below).

World renowned scientist James Watson, from the famous Watson & Crick team that discovered the DNA structure, recently sequenced his own genome. His discovery didn’t earn him the next Nobel prize for science, but he found out that he belongs to the elite few people whose body is more sensitive to ß-blockers. Now James Watson finally realized why it was so difficult for him to balance his blood pressure. It definitely paid off for Watson to sequence his own genome since he could significantly reduce his weekly ß -blocker intake. But despite this “health-changing” experience, he forbid his colleagues to reveal any information about his likelihood to develop Alzheimer. He said, “since you cannot cure it why would you like to know about it?”

The second candidate to share his experience after he personally sequenced his genome is Stanford geneticist Michale Snyder. His genome sequencing revealed that he was at high risk to develop Type 2 diabetes. A few months after his discovery, Synder got the disease that his genome anticipated. Was this a coincidence or fate? For Snyder, knowledge about his genome gave him a head start against the disease.  By completely transforming his diet and participating in various sport activities,  he overcame his Type 2 diabetes.

From my perspective, both examples show that knowledge about our genetic information can be useful in preventing and treating diseases. It boils down to how much experience exist to reliably interpret the data.

A documentary titled “Cracking Your Genetic Code” was recently released, and it offers a glimpse on how genomics is transforming medicine. Prominent scientists are featured, including Francis Collins from the National Institute of Health and Eric Lander from the Massachusetts Institute of Technology. In the documentary we are introduced to technologies for sequencing the entire genome; Illumina is being mentioned as one of the companies with such technology. We hear real-life stories where genome sequencing and genotyping led to diagnoses and successful treatments that would not happen otherwise.

The documentary does not only present the promises that personalized medicine is bringing, it also raises important questions concerning the readiness of the society in adopting this new form of medicine. There are always pros and cons with introducing new technologies to our daily lives. It is a matter of engaging and educating the public so the society as a whole can make some informed decisions during this healthcare revolution. Cracking your Genetic Code is a great introduction to the new role of sequencing in medicine, and I hope you will share it with your colleagues and friends!

John Lauerman, reporter with Bloomberg News got his genome sequenced. He is part of the Human Genome Project of the harvard medical school, where 10 genomes have been sequenced and analysed so far (Bloomberg).

After receiving his result he was first relieved to find no hint to have the APOE4 gene variant that raises the risk of Alzheimer’s disease. But what he learned then is that “No news wasn’t always good news; it just wasn’t bad news”. (Bloomberg) The researchs told him that the sequencing simply didn’t reveal information about APOE4. A study update however revealed later that the APOE4 gene variant indeed is present in his genome. This variant means an approx. 3 percent increased risk of developing the disease by age 80. But what does that mean in any single individual’s genome? At least Lauerman was less worried being his parents in the late 70s and 80s and having not developed Alzheimer’s disease.

But the researches have found in addition the rare JAK2 variant in Lauerman’s genome that is linked to a cancer-like blood disorder.  Knowing the risk, he now has the chance with increased vigilance to evaluate a potential disease early and to react accordingly.

And in that context Lauerman pointed out an even more important point: as a reporter working on a story about genomics, he had access to experts and genetic counselors that many people wouldn’t. What will happen as more people get results from broad genome sequencing? (Bloomberg) The question is if people can even handle the reports.

So as a personal conclusion I suppose I would be worried to hell when I would get to know my genome disorders. But it might be also a good thing, like in John Lauerman’s case. You would have the chance to detect a potential disease in an very early stage. You never know…

In an interview published in the online version of Germany’s well-known weekly news magazine Der Spiegel, the medical ethicist and philosopher Prof. Urban Wiesing describes the concern of German scientists’ about some companies that offer analysis of private genome data via the internet.

As today’s gene diagnostics provide in most cases only information about increasing or decreasing risk of developing multifactorial diseases like lung cancer, diabetes or Alzheimer’s disease, he states that these results are in most cases only of limited informative value. Body weight, eating habits as well as physical activities often do tell much more about the risk of developing e.g. diabetes type II.
Nevertheless Prof. Wiesing thinks that such tests will be worth consideration once the predictive value gets better in the future. Today he compares the informational value of such tests with an oracle.

The researchers are most worried about the fact that customers of such companies receive critical results without any face to face consultancy from medical experts. They share our opinion that it is absolutely necessary to explain these complex results and the implications they MAY have for the life of the patients (and their families) in an appropriate way. It is not without reason that such internet companies are forbidden in Germany.

What is your opinion? Would you like to know that e.g. your risk for developing diabetes type II is 30% higher than on average? Do you think you really would change your lifestyle in that case?

During my routine scan through the news on GenomeWeb I encountered an interesting article from Christie Rizk Knowledge of Genome Can Both Simplify and Complicate Knowledge of Self. This article is about the book My Beautiful Genome from Lone Frank who is a scientific journalist with Ph.D. in neurobiology.

On the homepage of Lone Frank you can find a sneak peek and these 6 pages contain already so many insights into human thinking and facts about the genome, that you really start thinking about your genome. Would you really like to know, if you had a hereditary disease? On the other hand it might be an extremely happy moment in your life when you learn that you don’t have a specific gene variant that is present in one of your parent’s genome.

I totally agree that we need research on the genome, since we need to know more about genes and their impact on our lives. In your private life your personal genome can provide information whether there is increased risk for a selection of hereditary diseases. Despite that it is still your decision and responsibility whether and to what extent you like to work with your personal data, isn’t it?

Knowing one’s genome may however also a fatal decision. What, if you find out a predisposition for a disease that cannot be treated?  This may even cause severe psychological problems .  In this context it is frightening that  some companies try to make money with dubious tests that have no scientific justification. What do you think?

Recently I saw this sign on a house in the China Town of Singapore, advertising for “Genetic Testings for Health and Innate Talents”. Having a look on their homepage > I could find that they have two main objectives:

1. Discovery of genetic variations that contribute to disease risk. (Disease Susceptibility Genetic Test or Genetic Predisposition Test)
2. Discovery of genetic variations that contribute to intelligence, personality characteristics, superior athletic performance, vocal ability, dancing ability, and other areas where humans can excel. (Innate Talents & Traits Genetic Test)

Obviously a lab in the US is testing some SNPs on Affymetrix Arrays > for them. It is not clear what they are testing, especially in terms of “Innate talents”. They have some testimonials > that do not really say much. With or without knowing a genetic disposition it makes sense to take care on ones diet and exercise the body. If an inherited disease is known in the family, it is wise to be careful and observe the body. Many genetic markers are only linked to a disease at a low percentage of penetration, but there is no guarantee that the carrier develops the disease later. Often this is a severe psychological burdon and requires genetic and psychological consulting.

Even more suspicious is the testing for “Innate Talents”. What is really known about it and how far shall we go?