Tag Archives: genetic testing

Prepare NGS for clinical use

Molecular diagnostics (MDx) is to my opinion the most sensitive application for all kinds of molecular biology techniques like PCR, Sanger Sequencing or Next Generation Sequencing. Today, NGS is still a niche application and needs further improvement to be a common tool for MDx. One thing that is lacking is the standardisation of NGS for clinical use.

The NGS Working Group, established by the Friends of Cancer Research worked out a master plan (The ASCO Post), with critical points that need to be addressed to use NGS more commonly:

1. Define a regulatory pathway for cancer panels (a selection of multimarker gene assays) intended to identify actionable oncogenic alterations (those with supporting data to create risk-benefit assessment of treatment choice) that allow flexibility in the appropriate FDA medical device pathway—for instance, one based on risk classification of different panel components depending on the specific marker.

2. Approaches to validation studies should be based on the types of alterations measured by the assay rather than on every alteration individually.

3. Determine the contents of a cancer panel by classifying potential markers based on current utility in clinical care and clinical trials and peer-reviewed publications, as well as recognized clinical guidelines. Draw upon various sources to determine the recommended marker set for an actionable cancer panel.

4. Promote standardization of cancer panels through development and use of a common set of samples to ensure reproducibility on each platform.

5. Establish a framework for determining an appropriate reference method rather than relying on any single method for all studies.

Get more information to each proposal here.

Quality Before Quantity?

The  “$1.000 genome” is to my knowledge the buzzword everyone knows when thinking about Next Generation Sequencing.

And quite often I ask myself: What will be the future of NGS? Whole genome sequencing of everyone and everything?

I am confident that this is part of Illumina’s  strategy for their new HiSeq X Ten instruments – at least for humans.

Contrary there is still all the data that needs to be analysed. And an interview with Lex Nederbragt highlights that data analysis is still a bottleneck. Also the latest report from Markets&Markets for whole exome sequencing predicts a strong growth in targetd sequencing. They estimate a growth for whole exome sequencing  from $326.6 M in 2013 up to $884.1 Million by 2018.

So will quality, like sequencing distinct regions outcompete the $1,000 genome? What are your thoughts about that?

Unexpected Heroes

Image courtesy of FreeDigitalPhotos.netThere are several mutations known which are linked to childhood diseases. This knowledge is already being used e.g. to analyze genomes of sick newborns for any known diseases, or for prenatal diagnostics. However: A person carrying such a mutation must not necessarily get ill.

Some individuals carry a mutation that should have caused a severe disease in their childhood. However, some yet unknown factors have protected them from getting ill. Even though they may be very rare, studying such persons may help to understand more about the diseases, or even find new treatments.

Researchers of the “Resilience Project” are now looking for such individuals who they call “unexpected heroes”: Adults who are “resilient to a certain rare disease despite carrying genetic mutations that would indicate onset of the disease in childhood.” In order to find those rare individuals, they are asking for volunteers to donate DNA samples for the project. Since they expect only 1 of 20,000 individuals to be such an “unexpected hero”, they need to analyze the genomes of more than 100,000 individuals. Participants can register online and will receive a test kit by mail. In return, the volunteers get a report indicating whether any of the analyzed mutations have been found in his or her genome.

The researchers hope to identify genes that can “buffer” the effects of the mutations, as well as environmental factors which help people carrying the mutations to stay healthy. The goal is to find new treatments, or even prevent people from getting ill at all.

Why is Illumina so successful? Watch an interview with Illuminas CEO

In the 2nd quarter of 2014 Illumina reported adjusted earnings of 57% per share – most probably the biggest increase in the companies history. Watch this interview with the CEO of Illumina, Jay Flateley, to learn more about the reasons of Illumina’s success.


GENReport: NGS Trends In Cancer Research & Clinics

GENReport_Publication growth
Enal Razvi, Ph.D. from SelectBio U.S. summarised very nicely the trends of next generation sequencing in cancer research and cancer diagnostics for Genetic Engineering & Biotechnology News.

Visit the GEN website to download the complete PDF report.

Cardiologists are the next target group

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.

Think Big: American Gut Project Based On NGS

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.”

Whole Genome Sequencing of Fukushima’s People

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.

NGS goes to the Big Apple

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.

Genomics – A Curse Or A Blessing?

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.