My personal and professional adventure into Science

Archives for 2013

FDA shuts down 23andme home gene testing kits

The genetic startup company 23andMe Inc, co-founded by Anne Wojcicki (who recently separated from Google co-founder Sergey Brin), Paul Cusenza, and Linda Avey, was told by FDA to stop the sales of their home testing kits as of 22. November 2013. 23andMe is giving the ability to test your health risk to more than 120 diseases, carrier status of more than 50, drug response to 25 drugs and will furthermore test you for 60 traits. All the above mentioned can be found here.

23andmeI have always considered the 23andMe results as guidance and not facts, and I also always recommend my friends to do that. The FDA is concerned that the test results would lead a patient into self-treatment, where the test results would probably lead the patients to talk with their doctors instead. It is noticeable that the FDA is not citing any examples of patients being harmed through the screening kit from 23andMe.

Of more fun stuff you will also be able to track your ancestry, so besides testing myself I also tested my 98-year-old grandfather. By doing that I can now see exactly what I share genetically with him. Furthermore I also found out that I share DNA with some people from work. It’s a small world out there 🙂

23andMe was founded in 2006 and now with more than 400,000 individuals in their database the company is definitely in growth.

The FDA letter can be seen: here.

Techcrunch news: here.

Bloomberg news: here.

 

Ancient Horse project among the top10 research projects in Denmark of the year 2013

I am delighted to say, that our ancient horse project Bent and horsehas been selected as one of the top10 research projects in Denmark of the year 2013.

The 10 projects have been selected by the editorial board of videnskab.dk who could choose from 56 candidates. It is still possible to vote for the projects, so please go and vote for the horse 😉
Unfortunately the page is only in Danish, but you should still be able to vote. Our project is called: 700.000 år gammel hest får sin arvemasse kortlagt.

Vote for the project Here

Oxford Nanopore launches MinION late November

Today it was announced that Oxford Nanopore will launch an early access to their MinION Access Programme (MAP) late November. To participate in the program one has to pay a $1,000 refundable deposit to receive the MinION USB device. Sequencing Preparation Kits will be provided from Oxford Nanopore, but it is said that a MAP participant may choose to develop their own sample preparation and analysis methods, under an unsupported basis according to the Oxford Nanopore Website

Oxford Nanopore MinION

About the programme

A substantial number of selected participants will receive a MinION Access programme package.  This will include:

  • At least one complete MinION system (device, flowcells and software tools).
  • MAP participants will be asked to pay a refundable $1,000 deposit on the MinION USB device, plus shipping.
  • Oxford Nanopore will provide a regular baseline supply of flowcells sufficient to allow frequent usage of the system.  MAP participants will ONLY pay shipping costs on these flowcells.  Any additional flowcells required at the participants’ discretion may be available for purchase at a MAP-only price of $999 each plus shipping and taxes.
  • Oxford Nanopore will provide Sequencing Preparation Kits.  MAP participants may choose to develop their own sample preparation and analysis methods; however, at this stage on an unsupported basis.

What are the terms of the MAP agreement?

Participation in the MAP product preview program will require participants to sign up to an End User License Agreement (EULA) and simple terms intended to allow Oxford Nanopore to further develop the utility of the products, applications and customer support while also maximising scientific benefits for MAP participants. Further details will be provided when registration opens, however in outline:

  • MAP participants will be invited to provide Oxford Nanopore with feedback regarding their experiences through channels provided by the company.
  • All used flow cells are to be returned to Oxford Nanopore3.
  • MAP participants will receive training and support through an online participant community and support portal.
  • MAP participants will go through an initial restricted ‘burn-in’ period, during which test samples will be run and data shared with Oxford Nanopore.  After consistent and satisfactory performance has been achieved under pre-agreed criteria, the MAP participants will be able to conduct experiments with their own samples. Data can be published whilst participants are utilising the baseline supply of flowcells.
  • MAP participants  or Oxford Nanopore may terminate participation in the programme at any time, for any reason. Deposits will be refunded after all of the MAP hardware is returned.
  • MAP participants will be the first to publish data from their own samples. Oxford Nanopore does not intend to restrict use or dissemination of the biological results obtained by participants using MinIONs to analyse their own samples. Oxford Nanopore is interested in the quality and performance of the MiniION system itself.
  • Oxford Nanopore intends to give preferential status for the GridION Access Programme (GAP) when announced to successful participants in the MinION access programme.
  • The MinION software will generate reports on the quality of each experiment and will be provided to Oxford Nanopore only to facilitate support and debugging.

Registration process

Registration will open in late November for a specific and limited time period.  Oxford Nanopore will operate a controlled release of spaces on the programme.

MAP participants will be notified upon acceptance to the programme. They will then able to review and accept the EULA  before providing the refundable deposit and joining the programme. MAP participants will then receive a login for the participant support portal and a target delivery date for their MinION(s) and initial flow cells.

The online participant support portal will provide training materials, FAQs, support and other information such as data examples from Oxford Nanopore. It will also include a  community forum to allow participants to share experiences.

US government shutdown of science

Today I saw a blog post by Jonathan Eisen with screenshots of some of the US governmental websites that are affected by the government shutdown.

Take a look, it’s pretty crazy 🙂

US government shut down science

 

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Are you a good teacher?

Every Friday we have a CBS group meeting where all staff is suppose to attend. Each week it will be a different group presenting exciting new discoveries, tips & tricks or whatever they choose to talk about. Once per month the subject is teaching, and today Irene presented a bit differently than usual, she showed us three small videos 🙂

During my Teaching & Learning course at DTU we used a book by Professor John B Biggs on the subject of Constructive Alignment. The book is titled Teaching for Quality Learning at University: What the Student does (Society for Research Into Higher Education).

Constructive Alignment is a principle used in teaching and learning, which is not typically used in traditional lectures and examinations. Often, you unfortunately see, that the learning objectives are not aligned with the examination method, which means that students who does not get into the deeper learning can be lost in the process. If the student is only interested in passing the course, he/she will typically look on what is required to pass the course. You have probably all heard questions like “Will this be in the exam?“, “Do we really need to remember this to pass the course?” etc. If the learning objectives are not well aligned with the requirements for the assessment method, these students will typically only read up on what is required to pass the exam and not get into the deeper learning.

Using constructive alignment will force these students to actually learn the subject the teacher intended the student to learn.

Århus University created three award-winning movies illustrating this, which I can only encourage you to watch if you want to improve your teaching.

Check out the videos below, they are short and to the point!
Also, feel free to give me your opinion in the comment box 🙂

Video 1/3

 

Video 2/3

 

Video 3/3

 

Relaxing in Vienna

After only having one week of vacation since I visited Australia in February, I decided to take some days off. I am now in Vienna where I will visit two friends I met at a summer school in Lipari 3-4 years ago. My main holiday will still be saved for a winter vacation somewhere warmer than Denmark, or colder for that sakes if it includes a lot of ice, snow and mountains 🙂

The last weeks have been tough, or months for that sakes, lots of work work work and Monday + Tuesday, Henrik and I had 14 oral re-exams with students attending our Introduction to Bioinformatics course. It was sad to see that only 55% of the students passed this year vs. 80% last year. Same teachers, lectures, exercises and TA’s. Only difference was the students. This down going trend in passing was unfortunately also seen in other courses. I hope next year will be better 🙂

To quickly recharge, I found a nice hotel with a lot of relaxation options, if that is what I want. Most preferably I would have liked to take a week or two to a warmer country with nice beaches, cold drinks and a lot of nature to explore. Unfortunately this just didn’t fit my schedule now, so that will be later, and it will also be nice to catchup with Marta and Paweł 🙂

The hotel I found has a spa with whirlpool, steam bath, sauna, pool, massage and a gym. And also a strange thing called an Alphalounger. It looks weird, but apparently it should recharge your mind, body and soul. I will see if it works 🙂
So, there should be plenty of opportunities to recharge if the weather turns bad.

Fortunately weather is nice, it’s around 22-23 degrees and sunny. So I think I will continue exploring the city and see what I can find 🙂

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New method for identifying genotype-phenotype correlations in protein multiple sequence alignments

At my office we are four people working in three different groups. Edita and Leon work in the Immunological Bioinformatics group, Mette is in the Integrative Systems Biology besides being a guest member of Functional Human Variation, and I work in the Metagenomics group and is also a guest member of Functional Human Variation. The variation of research areas make our discussions really funny sometimes because our areas are so different. They often find it funny when I talk about my DNA from horses, zebras, quagga, giant squid, polar bear or other weird animals and/or species 🙂

Recently Leon published a paper for a project he has worked hard on for some time now, the relief was very visible in Leon’s face when it finally came online 🙂

The paper is describing a webserver named SigniSite, abstract is below.

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Identifying which mutation(s) within a given genotype is responsible for an observable phenotype is important in many aspects of molecular biology. Here, we present SigniSite, an online application for subgroup-free residue-level genotype–phenotype correlation. In contrast to similar methods, SigniSite does not require any pre-definition of subgroups or binary classification. Input is a set of protein sequences where each sequence has an associated real number, quantifying a given phenotype. SigniSite will then identify which amino acid residues are significantly associated with the data set phenotype. As output, SigniSite displays a sequence logo, depicting the strength of the phenotype association of each residue and a heat-map identifying ‘hot’ or ‘cold’ regions. SigniSite was benchmarked against SPEER, a state-of-the-art method for the prediction of specificity determining positions (SDP) using a set of human immunodeficiency virus protease-inhibitor genotype–phenotype data and corresponding resistance mutation scores from the Stanford University HIV Drug Resistance Database, and a data set of protein families with experimentally annotated SDPs. For both data sets, SigniSite was found to outperform SPEER.
SigniSite is available at: http://www.cbs.dtu.dk/services/SigniSite/.

 

http://nar.oxfordjournals.org/content/41/W1/W286.abstract

New method for mapping the protein signals between healthy and diseased cells

International collaboration: University of Tübingen researchers help develop a way to trace communication between cells.

My good friend Boumediene has just shown that hard work and perseverance really pays of. He and two other former employees of CBS finally got their new method published today in Nature Methods. I am proud of having such clever friends 🙂

Researchers at Memorial Sloan-Kettering Cancer Center in New York, working in collaboration with researchers at the Proteome Center Tuebingen (PCT), have developed a new method for identifying the cell of origin of intracellular and secreted proteins within multicellular environments. This technological advancement is particularly exciting because it will provide investigators with a new tool for comprehensive mapping of cell-cell communication, which is especially important in all aspects of cancer development, maintenance, and response to therapy. For example, this method could be used to study cell signaling events between normal and malignant cells in order to better understand the molecular mechanisms by which surrounding normal cells alter tumor growth and response to treatment.

Microscope image of human breast cancer cells (red) grown together with mouse fibroblasts (green). This mixed-species culture was used to validate the ability of the CTAP methodology to distinguish proteins from each cell population.

Microscope image of human breast cancer cells (red) grown together with mouse fibroblasts (green). This mixed-species culture was used to validate the ability of the CTAP methodology to distinguish proteins from each cell population.
Copyright: Nicholas Gauthier, Chris Sander, and Martin Miller

The technique, named cell type specific labeling using amino acid precursors (CTAP), exploits the inability of vertebrate cells to synthesize essential amino acids normally required for growth and homeostasis. A team headed by Dr. Nicholas Gauthier and Dr. Martin Miller at the Memorial Sloan-Kettering Cancer Center engineered cells to express amino acid biosynthesis enzymes, which enabled cells to grow on their own supply of amino acids produced from supplemented precursors.

Mass spectrometry analysis of peptides derived from a co-culture of CTAP-engineered human (red) and mouse cells (green) that become specifically labeled heavy and light, respectively.

Mass spectrometry analysis of peptides derived from a co-culture of CTAP-engineered human (red) and mouse cells (green) that become specifically labeled heavy and light, respectively.
Copyright: Nicholas Gauthier, Chris Sander, and Martin Miller

The team went on to show that supplementing heavy stable isotope-labeled forms of these precursors led to incorporation of heavy amino acids into proteins produced in enzyme expressing cells. Dr. Boumediene Soufi and Dr. Boris Macek from the PCT designed experiments that utilized quantitative mass spectrometry to search for proteins that contained these stable isotope labels. In this way, the cell of origin of both intracellular and secreted proteins identified in multicellular culture could be determined. By providing a means to link proteins directly to specific cell types, the authors believe that this new method will be useful in studies of cell-cell communication and biomarker discovery.

Further information about this method can be found at:  http://ctap.ms

Original Publication:

Nicholas P Gauthier, Boumediene Soufi, William E Walkowicz, Virginia A Pedicord, Konstantinos J Mavrakis, Boris Macek, David Y Gin, Chris Sander & Martin L Miller, Cell-selective labeling using amino acid precursors for proteomic studies of multicellular environments, Nature Methods  doi:10.1038/nmeth.2529

Link to Nature paper: Cell-selective labeling using amino acid precursors for proteomic studies of multicellular environments
 
Contact:
Dr. Soufi Boumediene
Tübingen University
Faculty of Science
Proteome Center Tübingen (PCT)
Phone +49 0701 29-70568
boumediene.soufi[at]uni-tuebingen.de
 

A genome world record – A 700.000 year old horse gets its genome sequenced

I can proudly say that I have been a part of this project for the last two years 🙂

Official press release written by press office at University of Copenhagen.

It is nothing short of a world record in DNA research that scientists at the Centre for GeoGenetics at the Natural History Museum of Denmark (University of Copenhagen) have hit. They have sequenced the so far oldest genome from a prehistoric creature. They have done so by sequencing and analyzing short pieces of DNA molecules preserved in bone-remnants from a horse that had been kept frozen for the last 700.000 years in the permafrost of Yukon, Canada. By tracking the genomic changes that transformed prehistoric wild horses into domestic breeds, the researchers have revealed the genetic make-up of modern horses with unprecedented details. The spectacular results are now published in the international scientific journal Nature.

DNA molecules can survive in fossils well after an organism dies. Not as whole chromosomes, but as short pieces that could be assembled back together, like a puzzle. Sometimes enough molecules survive so that the full genome sequence of extinct species could be resurrected and over the last years, the full genome sequence of a few ancient humans and archaic hominins has been characterized. But so far, none dated back to before 70,000 years.

Now Dr. Ludovic Orlando and Professor Eske Willerslev from the Centre for GeoGenetics have beaten this DNA-record by about 10 times. Thereby the two researchers – in collaboration with Danish and international colleagues – have been able to track major genomic changes over the last 700.000 years of evolution of the horse lineage.

Credit: Iben Julie Schmidt. http://www.ishot.dk/

Credit: Iben Julie Schmidt.
http://www.ishot.dk/

First, by comparing the genome in the 700,000 year old horse with the genome of a 43,000 year old horse, six present day horses and the donkey the researchers could estimate how fast mutations accumulate through time and calibrate a genome-wide mutation rate. This revealed that the last common ancestor of all modern equids was living about 4.0-4.5 million years ago. Therefore, the evolutionary radiation underlying the origin of horses, donkeys and zebras reaches back in time twice as long as previously thought. Additionally, this new clock revealed multiple episodes of severe demographic fluctuation in horse history, in phase with major climatic changes such as the Last Glacial Maximum, some 20,000 years ago.

The world’s only wild horse

The results also put an happy end to a long discussion about the so-called Przewalski’s Horse from the Mongolian steppes. This horse population was discovered by the Western world in the second half of the nineteenth century and rapidly became threatened. It almost became extinct in the wild by the 1970s but has survived until now following massive conservation efforts. The evolutionary origin of this horse, that shows striking physical differences compared to domesticated horses, as well as an extra-pair of chromosomes, remained a mystery. The researchers reveal now that the Przewalski’s horse population became isolated from the lineage leading to the present day domesticated horses about 50.000 years ago. As the scientists could detect similar levels of genetic diversity within the Przewalski’s Horse genome than in the genomes of several domestic breeds, this suggests that the Przewalski’s Horses are likely genetically viable and therefore worthy of conservation efforts.

True Single DNA Molecule Sequencing

The geological context and dating information available was very strong and was built on about ten years of field work and research, carried out by Dr. Duane Froese, University of Alberta, and his team. Additionally, cold conditions, such as those from the Arctic permafrost, are known to be favourable for DNA preservation. But even so:

– Sequencing the first genome from the Middle Pleistocene was by no means straightforward, says Dr Ludovic Orlando who, together with his team, spent the most of the last three years on this project.

The researchers first got excited when they detected the signature of those amino-acids that are most abundant in the collagen as this could indicate that proteins had survived in situ. They even got more excited when they succeeding in directly sequencing collagen peptides. When they detected blood proteins, it really started looking promising because those are barely preserved. At that stage, it could well be that ancient DNA could also be preserved.

And indeed DNA was present. In tiny amount as the vast majority of sequences generated actually originated from environmental micro-organisms living in the bone. But with Helicos true Single DNA Molecule Sequencing, the researchers managed to identify molecular preservation niches in the bone and experimental conditions that enabled finishing the full genome sequence.

– This was methodologically challenging but clearly some parameters worked better than others, says Professor Eske Willerslev. But sequencing was just half the way really. Professor Willerslev continues:

– Because 700,000 years of evolution and damage, it is not something that does come without any modification to the DNA sequence itself. We had to improve our ability to identify modified and divergent ancient horse sequences by aligning them to the genome of present day horses.

Quite a computational challenge, especially when the level of DNA modification outcompasses that seen in any other Arctic horses from the Late Pleistocene. Dr. Orlando explains:

– Levels of base modifications were extremely high, for some regions even so high that every single cytosine was actually damaged. This, and the phylogenetic position of the ancient horse outside the diversity of any horse ever sequenced, provided clear evidence that the data was real.

Professor Willerslev adds:

– The results of the studies and the applied techniques open up new doors for the exploration of prehistoric living creatures. Now with genomics and proteomics, we can reach ten times further back in time compared to before. And new knowledge about the horse’s evolutionary history has been added – a history which is considered as a classical example in evolutionary biology and a topic which is taught in high schools and universities.

The new results are published in the scientific journal Nature.  This major scientific advance has been made possible through the collaboration with researchers from Denmark, China, Canada, USA, Switzerland, UK, Norway, France, Sweden and Saudi Arabia and with financial support from the Danish National Research Foundation.

At CBS we have used our supercomputers throughout the last two years to map all the 12 billions DNA fragments that were handed over to us from the people at GeoGenetics. Furthermore, we functionally annotated the donkey genome including the identification of Y chromosome associated contigs and assessed the metagenome of the Middle Pleistocene horse sample.

Link to Nature paper: Recalibrating Equus evolution using the genome sequence of an early Middle Pleistocene horse
Link to Nature news: First horses arose 4 million years ago

Ludovic Orlando, Aurélien Ginolhac, Guojie Zhang, Duane Froese, Anders Albrechtsen, Mathias Stiller, Mikkel Schubert, Enrico Cappellini, Bent Petersen, Ida Moltke, Philip L. F. Johnson, Matteo Fumagalli, Julia T. Vilstrup, Maanasa Raghavan, Thorfinn Korneliussen, Anna-Sapfo Malaspinas, Josef Vogt, Damian Szklarczyk, Christian D. Kelstrup, Jakob Vinther, Andrei Dolocan, Jesper Stenderup, Amhed M. V. Velazquez, James Cahill, Morten Rasmussen et al., Recalibrating Equus evolution using the genome sequence of an early Middle Pleistocene horse. Nature (2013) doi:10.1038/nature12323, PDF

Contact:

Dr. Ludovic Orlando: E-mail: orlando.ludovic@gmail.com;  Phone +45 21849646

Professor Eske Willerslev: E-mail: ewillerslev@gmail.com;  Phone +45 28751309

Ancient horse DNA provides new insights into evolution

This post is a teaser for tomorrow’s post and is directly taken and translated from Videnskab.dk, hence all credit should go to Line Fedders who wrote the original article in april 2013 and not me. This is a project I have been so fortunate to be involved in for the last two years 🙂

Horses are one of the species that have had the greatest impact on mankind. As food, transportation, in war and in the daily use and as pets. The horse’s appearance-related evolution from a small animal the size of a dog to today’s powerful beast is also well understood by scientists, but no one has yet looked at how the horse’s DNA has evolved in line with the look.

Credit: Iben Julie Schmidt

Credit: Iben Julie Schmidt
http://www.ishot.dk/

This is what a group of scientists at The Center for GeoGenetics at Copenhagen University is looking at with financial support from DFF.

The group, led by Associate Professor Ludovic Orlando, is currently investigating how the horse’s DNA has evolved, and it can provide new insight into how changes in the environment and man took and the subsequent domestication of horses have changed a species all the way into the DNA.

»Different breeds of horses can be seen as experiments, we humans have made and experimentation have created completely different horses. In this project we are able here to see which genes are changed in each experiment. We will be able to explain the processes, both man-made and environmentally made, biological drives the development of a horse’s appearance, “says Associate Professor Ludovic Orlando.

“We expect that some of the mechanisms we find are similar in all mammals, and thus the horse’s development also tell something more general about evolution,” he adds.

Will restore ancient horses

When Ludovic Orlando says that horses can be seen as experiments, we humans have made, he believes that by selecting certain individuals and give them benefits, such as food, or by direct breeding, selecting for certain traits. For example, size, strength or temperament.

The horse breeds that exist today, almost all bred by humans, and therefore can not be the basis of their DNA say something about how an original horse’s DNA looked.

“With this project here, we want to restore the horses, from before they were domesticated. We will create the profile for what a horse was before we made them the animals they are today, “says Ludovic Orlando.

Comparing across time

If the scientists successful can map the genome of the ancient horses, they will compare it with the genome of modern horse breeds and genome of the so-called Przewalski horse, which is probably the living race that has most in common with the ancient horses. Przewalski horses is an endangered wild horse that lives on the steppes of Central Asia, especially in Mongolia.

“In doing so, we examine whether the Prewalski-horse actually is the last living wild horse. If you look at cave paintings of 22,000 years ago the pictures of horses actually looks like Przewalski horses. By comparing the genomes we can see if they are genetically closer to the true wild horses that lived before the domestication of 5,500 years ago, or on horses today, “explains Ludovic Orlando.

The researchers have so far been mapped genome of a number of horses today to be used for the comparison. They have looked at the American Quarter Horse, thoroughbred horse, arabian horse, the Icelandic horse and the Norwegian horse, also known as North Bagge or Trotter.

“These breeds present all different breeding preferences. By going back in time and look at the family trees we have found horses that are as different as possible, “says the researcher.

Changing the limits for the possible

Ludovic Orlando and his colleagues are using the latest methods in DNA sequencing and repair of very-old DNA found among other fossils.

Scientists have DNA from horses, spanning many thousands of years. Just how ancient DNA, scientists will be looking at, he can not say yet. Scientists are namely in dialogue with the scientific journal Nature on an article, and it requires that they keep close.

“I can say that we are moving back long before the domestication of horses 5,500 years ago. We look at the DNA that is older than what you have done before, “says Ludovic Orlando.

Microbes stand in the way

Working on the ancient DNA takes place roughly at that scientists crusher bone fossils and extract the DNA. But it is not an easy task.

“We will sequence every one of these about six billion DNA letters that we expect the ancient horses DNA to have. However, it is technically challenging. Old DNA can survive, but it gets injured., “Explains Ludovic Orlando.

The hard part is that as soon as a creature dies, the cells explodes and in goes microbes which also contain DNA. Even if there were no microbes in the cell, there is water in the environment and remains of the tissue. The water degrades DNA into small pieces of sequences that break or change.

The researchers’ main job is to make sure that the DNA they look at, are from the horses and not from microbes.

“With our technology we can generate a billion DNA sequences of about five days. But we also get DNA from microbes in the ratio of 1:99. So there is 1% chance that we find what we’re looking for. It looks like a billion sequences, but actually it should be divided by 100, so we need to map a whole lot before we can hope to get everything we’re looking for, “says the researcher.

We want to understand the process

The methods that scientists use is constantly evolving, so they can be better. But it is the goal, not the means that interest Ludovic Orlando.

The methods are cool and innovative, especially for a molecular biologist. But we are looking for the answer. It’s the process we will understand. What we humans and the environment make that change the creatures, “he says.

Ludovic Orlando expects that the project will be started the next three years. The researchers have already come a long way, but there will always new side projects.

“We are studying among other horses who have been living under very cold conditions to see how the environment has affected their DNA. There are probably tons of projects and we are already in contact with lots of people, for example horses breeders in the United States. ”

 

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