Exellent summary of genes overepxpressed in different cancers and appeared in multiple studies. 6 pages, one table, a quick-start guide to observe gene expression peaks in cancer.

http://www.nature.com/nrc/journal/v10/n1/abs/nrc2771.html?lang=en

Nature Reviews Cancer 10, 59-64 (January 2010) | doi:10.1038/nrc2771 

A census of amplified and overexpressed human cancer genes

Thomas Santarius¹, Janet Shipley², Daniel Brewer², Michael R. Stratton¹ & Colin S. Cooper  About the authors

Boston University biomedical engineers have devised a method for making future genome sequencing faster and cheaper by dramatically reducing the amount of DNA required, thus eliminating the expensive, time-consuming and error-prone step of DNA amplification.

“The current study shows that we can detect a much smaller amount of DNA sample than previously reported,” said Meller. “When people start to implement genome sequencing or genome profiling using nanopores, they could use our nanopore capture approach to greatly reduce the number of copies used in those measurements.”

Currently, genome sequencing utilizes DNA amplification to make billions of molecular copies in order to produce a sample large enough to be analyzed. In addition to the time and cost DNA amplification entails, some of the molecules — like photocopies of photocopies — come out less than perfect. Meller and his colleagues at BU, New York University and Bar-Ilan University in Israel have harnessed electrical fields surrounding the mouths of the nanopores to attract long, negatively charged strands of DNA and slide them through the nanopore where the DNA sequence can be detected. Since the DNA is drawn to the nanopores from a distance, far fewer copies of the molecule are needed.

Before creating this new method, the team had to develop an understanding of electro-physics at the nanoscale, where the rules that govern the larger world don’t necessarily apply. They made a counterintuitive discovery: the longer the DNA strand, the more quickly it found the pore opening.

“That’s really surprising,” Meller said. “You’d expect that if you have a longer ’spaghetti,’ then finding the end would be much harder. At the same time this discovery means that the nanopore system is optimized for the detection of long DNA strands — tens of thousands basepairs, or even more. This could dramatically speed future genomic sequencing by allowing analysis of a long DNA strand in one swipe, rather than having to assemble results from many short snippets.

“DNA amplification technologies limit DNA molecule length to under a thousand basepairs,” Meller added. “Because our method avoids amplification, it not only reduces the cost, time and error rate of DNA replication techniques, but also enables the analysis of very long strands of DNA, much longer than current limitations.”

With this knowledge in hand, Meller and his team set out to optimize the effect. They used salt gradients to alter the electrical field around the pores, which increased the rate at which DNA molecules were captured and shortened the lag time between molecules, thus reducing the quantity of DNA needed for accurate measurements. Rather than floating around until they happened upon a nanopore, DNA strands were funneled into the openings.

By boosting capture rates by a few orders of magnitude, and reducing the volume of the sample chamber the researchers reduced the number of DNA molecules required by a factor of 10,000 — from about 1 billion sample molecules to 100,000.

The research was funded by the National Human Genome Research Institute of the Institutes of Health and by the National Science Foundation.

Story Source:

Adapted from materials provided by Boston University College of Engineering, via EurekAlert!, a service of AAAS.

As part of the final requirements for our DME capstone experience, the News Genome Project (formerly Project Fidelity) was asked to pitch our project to the Knight Foundation’s News Challenge program. We will update our text application with the final version of our proposal soon.

Until then, please check out this five minute video presentation explaining the News Genome Project and head over to our application on the News Challenge’s site.

view this video on vimeo

Scientists have decoded the entire genome of a couple of cancers, and more are on the way.

One day Helicos would make $1000 genome possible

An International team of scientists has sequenced the genome of the giant panda.  The findings were published this week online in the journal Nature.  This is the first genome project to rely solely on short-read next-generation sequencing technology.  This project is also the first in the bear family.  The sequencing project was able to identify that giant panda’s likely have all the necessary genetic components for a carnivorous digestive system.  Researchers speculated that the panda’s bamboo diet is influenced another aspect of its makeup, such as its taste receptors for meat.

Dan Vorhaus at Genomics Law Report launched a great series featuring many scientists, legal and social experts who talked about the possible implications in genomics. My commentary focused on the web 2.0 aspect of personalized medicine. Now the series is over and they published an e-book which is a must-read for everyone who wants to know more about the ELSI of genomics or personalized medicine.

From October 5 to December 8, 2009, the Genomics Law Report featured a series of thirty-six guest commentaries by industry, academic and thought leaders in the fields of genomics and personalized medicine. Entitled What ELSI is New?, the series, which we have organized into an e-book (pdf), asked each contributor to briefly respond to the following question: “What do you believe is the most important ethical, legal or social issue (ELSI) that must be addressed by the fields of genomics and/or personalized medicine?”

Article: Affordable genetic mapping of babies by 2019
Source: TimesOnline.com

A tiny prick of a baby’s heel is all scientists need to map the infant’s entire genome.  Currently, the cost can run anywhere from $10,000 to $100,000 depending on how many of the 6 billion DNA genes you’d like to map.  In 10 years, the cost will be sub $1000.

By examining genetic variations using genome mapping, doctors can predict illnesses you will be at a higher risk to get later in life.  This includes cardiovascular diseases, diabetes, cancer, and other dangerous illnesses.  Prevention measures can then be applied accordingly.

From a scientific perspective, it’s simple.  But it’s not that simple when you apply a moral and ethical lens to it.  What if your genome map is disclosed to insurance companies, employers, potential spouses, etc.?  What if it’s used for unintended purposes in the future?

This brings up the much-debated question: should society avoid applying or advancing any thought, technology, or invention that has potentially negative implications?  Most inventions are undoubtedly created and introduced for the benefit of society.  All inventions have the potential of being used incorrectly.  The invention isn’t at fault, but instead, the person’s motives are.  Often time, even the someone’s motives are virtuous, the ramifications of their actions harm society as a whole.  It’s a messy equation that’s more gray than black/white.

One resolution to this dilemma is to regulate who can use genome sequencing and for what purpose.  For example, there is legislation in the works to ban insurance companies and employers from using your genome to make business decisions (i.e. – increase your insurance premiums if your genome mapping data says you’re at a higher risk for a particular disease).  However, corporations are rather resourceful and have legions of highly-paid and connected lawyers and lobbyists who can make wishes come true with time, persistence, and money.  It’s not a matter of if, it’s a matter of when they succeed to do as they please.

So with that in mind, the question is a simple one: should we prevent new inventions and findings from emerging in society for the fear of misuse, or should we rely on regulation to prevent it’s misuse?  Or, is there another solution altogether….?

This is the title of our latest paper in Molecular Cell:

http://www.cell.com/molecular-cell/fulltext/S1097-2765%2809%2900857-0

With a nice accompanying article by Prensner and Chinnaiyan:

http://www.cell.com/molecular-cell/abstract/S1097-2765%2809%2900860-0

And a story on the Princeton web site:

http://www.princeton.edu/main/news/archive/S26/04/69Q40/index.xml?section=topstories

Dec 22, 2009: the paper is the most downloaded article in Mol Cell within the last 30 days

http://www.cell.com/molecular-cell/mostread

The Council of Scientific and Industrial Research successfully completed the first ever Human Genome Sequencing In India.

The Council of Scientific and Industrial Research (CSIR) has achieved the feat of successfully completing the first ever Human Genome Sequencing in India. Scientist of CSIR at the Institute of Genomics and Integrative Biology (IGIB), Delhi have sequenced the Human Genome of an anonymous healthy Indian citizen.

Addressing a press conference held here today Union Minister  Prithviraj Chavan said that this feat is unique in the sense that it has been achieved by a team of very young scientists. CSIR has been endeavoring to nucleate such teams in different niche technological areas as per the directive of Hon’ble Dr. Manmohan Singh, President, CSIR and Prime Minister of India. This initiative is paying off.

Elaborating the details of research on Human Genome, Chavan  said that the first Human Genome Sequence in the world was a result of the International Human Genome Project comprising scientists from United States, United Kingdom, France, Germany, Japan and China. The Project formally started in 1990 and the sequencing was completed in 2003. This spectacular feat at that time was hailed equivalent to the man landing on the moon. India could not be a part of this large initiative as in the early nineties it lacked the necessary resources.

“With the completion of the first Human genome sequence in India, the nation is now in the league of select few countries like United States, China, Canada, United Kingdom, and Korea who have demonstrated the capability to sequence and assemble complete human genomes. CSIR could achieve this by adopting new technologies and by effectively integrating complex computational tools with high throughput analytical capabilities”,  said Prithviraj Chavan.

While the first Human Genome Sequence effort took more than a decade spending over a billion US dollars, CSIR scientists at IGIB finished the complete sequencing and assembly in much shorter time comparable with similar recent effort the world over. By using next generation technologies and skills, they successfully bridged the technological gap that existed a decade ago.

Sh. S.K. Brahmchari, DG, CSIR informed that the Human Genome has 3.1 billion base pairs. The team at IGIB generated over 51 Gigabases of data using next generation sequencing technology, resulting in over 13x coverage of the Human Genome. This next-generation sequencing technology enables massively parallel sequencing of millions of genomic fragments of 76 base pairs, which are then mapped back to the reference genome. This humongous exercise was made possible with the CSIR supercomputing facility at IGIB.

The sequencing of the first Human Genome in India in conjunction with Indian Genome variation programme opens newer vistas for low cost affordable healthcare and predictive medicine in future for the masses. This also opens up newer possibilities in disease diagnostics, treatment and sustaining low-cost drugs in the market.

Courtesy : Press Information Bureau

Much like Bar Refaeli and Leonardo DiCaprio, DNA Sequencing and cloud computing go hand in hand together.

I had a  very  interesting conversation with a friend yesterday about DNA Sequencing and cloud computing.

My friend is leading one of the largest cancer genome research projects in the world (and  yes, he is extremely  bright).

It appears that there is a great progress in DNA sequencing technology, based on chemical process. The pace is much faster than Moore’s law. As a result the budgets are shifting from the chemistry side to the computational side.

In the past, the budget would be 90% for biology and 10% for analyzing the data coming our of the DNA.

As the sequencing costs have fallen by orders of magnitude there is more and more data ( a single patient genome data is one TeraByte).

The more data , the more computing power needed to analyze it and hence the budget split becomes 50-50.

Each computation can take up to 24 hours, running on 100 cores mini grid.

In theory, such tasks are great for cloud computing IAAS (Infra Structure as a Service) platforms or even PAAS (Platform as a service) solutions with Map-Redux capabilities.This EC2 Bioinformatics post provide interesting examples.

In practice there are three main challenges

1. Since Cancer research facilities need this server power everyday, it is cheaper for them to build the solutions internally.

1. To make things even more challenging, the highest cost in most clouds is the bandwidth in and out of the cloud. It would cost $150 to store one patient data on Amazon S3, but $170-$100 to transfer it into S3.

1. Even if the cost gap can  be mitigated, there can be regulatory problems with privacy of patients data.After all its one person entire DNA we speak about. Encryption would probably be too expensive, but spiting and randomizing the data can probably solve this hurdle.

So, where do clouds make most sense for this kind of biological research ?

One use case is the testing of new improved  algorithm. Then, the researchers want to run the algorithm on all the existing data, not just the new one.

They need to compare the results  of the new algorithm with the old algorithms on same data set.They also need to finish the paper on time for the submission deadline .

In such scenarios there is a huge burst of computation,needed on static data, at a very short period of time.Moreover,  if the data can be stored on shared cloud, and used by researchers form across the world, than data transport would not be so expensive in the overall calculation.

These ideas are fascinating and hopefully would drive new solutions, cures and treatments for cancer.

I just learned right now (this hour), that there is a holiday called the “National DNA Day”. This holiday commemorates “the completion of the Human Genome Project in April 2003, and the discovery of DNA’s double helix by Watson, Crick and Rosalind Franklin.” [1]

Very briefly, what does this mean?

Watson, Crick and Rosalind Franklin were a group of researchers (from the 1940’s) who were able to crystallize DNA and analyze it’s X-ray diffraction pattern. From that, they found that DNA is a double helix. The double helix refers to that twisted ladder structure (see bellow).  Now, figuring out the structure of DNA and it’s chemistry is a big deal, because that opened the door to a huge scientific boom in the field of biology. Now we can understand things like how bacteria and viruses work, and how to manipulated bacteria genetically (cloning) to make important chemicals (e.g. antibiotics and important enzymes for industry). Understanding DNA is a key achievement for the advancement of Biotechnology, Medicine, Pharmaceuticals …. you name it !!!

Ball and Stick model of the DNA

The Human Genome Project, basically was a huge research project that was funded by the NIH and it involved many participating countries to be completed. The project was to sequence the entire human genome. It, too, is a huge step form humanity (more important than landing on the moon ) because it helped us understand how truly complex the human body is. It also provided an understanding of genetic defects and how it affects human health (e.g. cystic fibrosis, color blindness, down syndrome).

Human Genome Project Logo

[1] http://www.biojobblog.com/articles/ideas-and-indulgences/

WC = 2454

Work-In-Progress

Genre: Speculative Fiction

Title: “Waging Peace”

The defense think-tank, hidden deep beneath the mountain range, is unknown to all but a few in high government.

The lead scientist now approaches the podium to address an audience of scholars, ethicists, legal experts, religious leaders, and a small host of high rank military.

The public address system hums momentarily as an engineer adjusts the microphone.

The screen on the wall behind the podium proclaims only five stark words:

Permanent Endocrine Activase Containment Ethnocide

The scientist begins to address the audience:

“As we all know, the code name for this project is P-E-A-C-E. Today we have assembled here to debate and vote upon the deployment of this new technology which has acquired the nickname PEACEFUL WAR.”

(A low nervous laughter ripples through the audience.)

“The vaccine which we have developed is specific to genetic traits peculiar to our enemy’s ancestry. When the agent of the vaccine enters a human body through the skin and encounters those specific genetic codes, it activates and proceeds to integrate itself into the genetic structure of every cell, causing permanent sterility in both males and females, by prohibiting the chromosomal reduction division necessary for fertilization. The affected individuals are totally unaware of what is happening to them. There is no pain, no illness, no side effects. The only symptom is sterility in men and barrenness in women. “

Several professors of Ethics voice their objections on the morality of deploying such a technology.

Then, the spokesperson for the military generals steps to the podium:

“I have been asked to address you today and enumerate those reasons in favor of deploying
P-E-A-C-E. I have decided to read to you a lecture which I heard many years ago, at West Point, from my professor of military ethics, entitled,

“Morality vis a vis Military Strategic Objectives”

The General begins to read a transcript of the old Academy lecture:

“War is never moral; it is at best unavoidable and expedient.

When a nation, or an alliance of nations, perceives some threat to their sovereignty, and when strategic targets or measures have been defined, whether it is of the scale of surgically precise missile strikes at bases or plants, in which a few dozen lives are lost, or whether it is of the scale of the landing at Normandy in which thousands of lives are lost, or the bombing Dresden or of Hiroshima and Nagasaki, in which hundreds of thousands of lives are lost, the fact remains that there is a price to be paid in terms of human life, both for the enemy and for the invading forces, and the magnitude of loss is defined and deemed reasonable and necessary. That price is in terms of human lives lost, on both sides. Casualty and death is an unavoidable aspect of military actions. Whether only one life is lost, or ten lives or one thousand lives, or a million lives, is not an issue. We tend to think nothing of the news report of ten fatalities. We are alarmed by one thousand fatalities. Should the fatalities reach one million we are revolted by what we perceive as a morally reprehensible destruction of human life. Yet the simple fact remains that any human life is of inestimable value, and taking one life is no more or less disturbing than the sacrifice of 100,000 lives or even a million lives, provided the strategic goal justifies the magnitude of the loss. It is not the number of lives lost, but the justification of such losses from a strategic point of view. If the loss of human life amounts to an entire city, or even an entire nation, we categorize the event as a genocide or ethnocide or holocaust. But, from a strategic military perspective, the value of the objective is weighed against the loss of life, and hopefully, strategists are motivated to take no more lives than might be considered necessary and justified to achieve a victory. Military and strategic victory will never be equivalent to a moral victory. War and killing is never moral. And there is no war without the taking of human lives.

In retrospect, with historical hindsight, we can say that it was not necessary to destroy the entire German or Japanese people in order to put an end to Hitler and the Nazis in World War II. We can see that the German and Japanese people of today are not the same kind of “ideological” threat as they were in the 1930’s. Times change, people change, nations change. Even the peoples of the former Soviet Union are not quite the same as they were in the 1950’s. Chinese ideology poses a threat today, but I dare say one does not yet think of the annihilation of China as a solution to ensure world peace and democracy.

Where am I heading with this train of thought? I am simply posing a theoretical situation in which one part of the world perceived an “ideological” threat of such magnitude, that the wide-scale annihilation of an entire nation might be proposed as the only certain method to ensure a victory and peace. Current weapons of mass destruction are too damaging to the environment to be deployed on such a large scale as to achieve the annihilation of an entire nation in an efficient and timely fashion, and yet leave the land habitable and the natural resources usable. But, let us imagine, for the sake of argument, that clean, environmentally safe weapons of mass destruction were developed. And let us further imagine that an alliance of nations perceived an ideological threat of such magnitude that a simple military defeat and occupation would not ensure world peace. In such a hypothetical situation, it is conceivable that a strategic decision might be made to destroy the population of an entire country, and that the importance of the military strategic objective would outweigh the price in human life in the minds of those making the decision in favor of such a preemptive strike. No matter how heinous such a military action might appear to us, in terms of loss of human life, it is not more immoral simply because millions of lives are involved, rather than only thousands or hundreds of lives, since the taking of even one human life unnecessarily is in some sense no less worse than taking a thousand lives or a million lives. Strategists weigh the strategic importance of the victory against the price in casualty and mortality which must be paid.

It is not inconceivable that one day an ideological threat of sufficient magnitude might develop which would make the deployment of such weapons of mass destruction seem a reasonable, or perhaps even unavoidable, solution. “
(end of lecture)

The General continues,

“Some measures are ugly, but necessary. Somewhere, someone else, right now, is developing an entirely new weapon of mass destruction, environmentally safe, which will make genocide practical, quick, efficient. The race is on. At stake is the future of the human race as a whole, the future of democracy and freedom of speech, the future of intellectual curiosity.”

A Cardinal objects, “But what of all the innocent women and children?”

“The women and children are the real enemies, the breeding ground for the next century of ideological threat. If we do not exterminate them, then they shall rally and retaliate again and again, decade after decade, century after century. The free world will only be free from the threat of that ideology when their language is a dead language. If people thought that, tomorrow, cancer and aids could be eliminated by annihilating some species of animal, or microbe or virus, (without harming the ecosystem) then it would be done in a heartbeat. The day we discover that we were wrong, and that the ideological threat is a serious threat, but we took no action, then it will be too late to do anything about it, because we shall already be defeated and enslaved.”

An elderly retired professor of Philosophy raises his hand:

“Heisenberg wrote a book in the 1950’s about Quantum. In that book he made an interesting observation: namely, that once certain technologies come into use, just like those things which escaped Pandora’s box, they cannot be “put back in the box” again. Nuclear energy was what he had in mind. But stop and think, you cannot tell the world ‘Oh , sorry, but this Internet thing was a bad idea,’ or ‘sorry, but we must no longer use cell phones.’ Certain things, once they start, won’t go away. Democracy is like that , I suspect. Freedom is like that, free speech, human rights, inalienable rights. It starts with a “shot heard round the world”, but where does it end?

Perhaps our own extinction will be part of some divine justice. We once made the error of assuming that our planet was the center of the universe. We still assume that our existence and survival is of central importance to some divine will. Perhaps we really shall build a sci-fi version of Noah’s Ark, piloted by immortal cyborgs, transporting a genetics lab containing all terrestrial life and a library containing all human culture, in search of a new life in another galaxy. Noah’s ark does not make so much sense, until genetic engineering comes along, and Jurassic Park.

Here is a favorite old Chinese Taoist saying of mine: ‘When the wrong person employs the right means, then the right means yield the wrong result.’

Did you ever hear the Taoist story about the farmer, who left his barn door open, and his one horse escaped, so he was very sad, but his neighbor said ‘be neither sad nor happy for we cannot see to the ultimate end of an event?’

A few weeks later, the horse return, and brought with him a herd of wild horses that he had befriended in the mountains, so now the farmer rejoiced, wealthy in horses, but again the neighbor warned ‘be neither sad nor happy, for we cannot see the end of a matter.’

The farmer’s son chose a wild horse for his own, and proceeded to break and tame the horse but was thrown, and his leg was broken. Now the farmer was sad. But once again the neighbor advised ‘be neither sad nor happy.’

A few days later, the king marched by the farm looking for young soldiers for his army, to go off to battle in a distant land. But when he saw the son with his broken leg, he said ‘this one is useless to us’ and left. Now the farmer rejoiced, that his son was spared. But still the neighbor cautioned ‘be neither sad nor happy.’ “

The professor concluded and the general sighed and continued.

“If I see a dog running through the streets with rabies, I feel no anger, but I shoot the dog, partly from compassion for the dog, and also for my own survival.

For centuries now, we have been waging war. For the first time in history, we have the opportunity to wage peace.

You see, we can wage all the conventional wars we please. But as long as some of the people survive, then, in a few generations, they will raise up more fundamentalist terrorist guerrilla fighters, so the terrorism will go on for decade after decade, generation after generation, because their IDEOLOGY their belief, will never disappear. It will only disappear if every man woman and child disappears who speaks the language of their ideology, nursed in the cradle and culture of such beliefs.

Supposedly, we are always fighting for the sake of achieving some future peace or preserving freedom and avoiding tyranny/dictatorship/slavery/oppression.

Peace, so far, historically, is an illusion, because there always seems to be a war going on somewhere. It is a “catch-22″ situation. There is no hope of future peace and an end to war unless one ideological side totally annihilates the other side (which is genocide/ethnocide), but that is considered a terrible crime. Yet all war and killing is an evil . Who can say! Perhaps it is the greater evil to fight conventional wars for centuries, and never have peace rather than bite the bullet, commit genocide, and once and for all eliminate the opposition, so that the surviving world would all be homogeneous in ideological beliefs.

But then, even if America, Canada, Great Britain, Australia, New Zealand (etc. whoever you see as alike, homogeneous) if they were to annihilate all other nations (whoever you see as the enemy), well, there is no guarantee that the surviving peoples, after 100 years, would not evolve factions of ideological difference, and be at it all over again . Einstein and Bohr and Heisenberg and the other physicists felt regret that they had unleashed this terrible power of nuclear destruction. Look at the scientist, Nobel, who invented dynamite, an explosive. One day, a newspaper mistakenly received the news that Nobel had died, so they printed his obituary, as the man who invented dynamite. When Nobel read this, he decided to leave his fortune to make the Nobel Peace Prize, because he did not want to be remembered only for the destructive power of explosive dynamite.

All of history is like a constantly swinging pendulum, swinging back and forth between various opposites; between wealth and poverty, war and peace, conservative and liberal, debauchery and temperance, religious fervor and atheism, like a grandfather clock. The people made strong say by slavery, or poverty, or suffering, or the challenge of pioneering effect some great change. But then next generation, which is has it easy, in affluence, or peace and safety, why, they loose that pioneering super-hero spirit and become flabby physically and spiritually. There is never any end, never any peace, never any balance or equilibrium where the pendulum stops swinging. We are always struggling and fighting for peace, prosperity, freedom, morality. But we never achieve peace. We are never free. We never eliminate poverty and we are never collectively moral. It is only under suffering and adversity that a people develops the courage and character to seek revolution and reform. The peace and prosperity of that reform and freedom leads to a weak character, to decadence, to decay and corruption, so the cycle repeats all over again.

The physicist, Robert Oppenheimer, was an observer at Los Alamos when they tested the very first atomic bomb (before they bombed Japan). When he saw the mushroom cloud, he spontaneously quoted a verse from the Bhagavad-gita (a Hindu scripture)… where God says, “I am become Death, destroyer of worlds.”

On the one hand, people were war weary, and willing to do anything to end it. But, on the other hand, they saw that this new technology was like “Pandora’s box” and that the demon of nuclear weapons had escaped and there was no putting it back in the box.

Two members of the lab (Huimin and Olivier) will be attending the ASH2009 meeting in New Orleans.

Here is the poster we will present at the meeting:

http://physiology.med.cornell.edu/faculty/elemento/lab/files/EZH2_ASH_2009_poster.pdf

And the corresponding abstract on the ASH web site:

http://ash.confex.com/ash/2009/webprogram/Paper25356.html

I’m often asked how much entropy there is in the DNA profiles used in forensic investigations. Specifically, is it more than 33 bits, i.e., can it uniquely identify individuals? The short answer is: yes in theory, but there are many caveats in practice, and false matches are fairly common.

To explain the details, let’s start by looking at what is actually stored in a DNA profile. Your entire genome consists of billions of base pairs, but for profiling purposes, only a tiny portion of it is looked at — specifically, 13 locations or loci (in the U.S. version, which I will focus on. The U.K. version uses 10 loci.) Each of these loci yields a pair of integers which varies from person to person. You can see an example DNA profile on this page.

The degree of variation in the pairs of numbers — genotypes — at each locus has been empirically measured by many studies. Since biological laws dictate that the genotypes at different loci are uncorrelated, we can calculate entropy by simply adding up the entropy at individual loci. I analyzed (source code) the raw data on variation at each locus from a sample of U.S. Caucasians, and arrived at a figure of between 3.0 and 5.6 bits of entropy per locus and 54 bits of entropy for the whole 13-locus DNA profile. In addition, there is 1 sex-determining bit.

Since that number is well over 33 bits, with a high probability there is no one else who shares your DNA profile. However, there are many complications to this rosy picture:

Non-uniform genotype probabilities. The entropy calculation doesn’t quite tell the whole story, because some genotypes at each locus are much more common than others. If you happen to end up with a common genotype in all (or most) of the 13 loci, then there might be a significant chance that someone else in the world shares your DNA profile.

Population structure. The calculation above assumes the Hardy-Weinberg equilibrium, which is only true if mating is random, among other things. In reality, due to the non-random population structure, there is a slight deviation from the theoretical value. This manifests in two ways: first, the allele frequencies for different population groups (ethnic groups) need to be calculated separately. Second, there is a deviation from the expected genotype frequencies even within population groups, which is more difficult to account for (a correction factor called “theta” is applied in forensic calculations).

Familial relationships. Since we share half of our DNA with each parent and sibling, there is a much higher chance of a profile match between close relatives than between unrelated individuals. Therefore DNA database matches often turn up a relative of the perpetrator even if the perpetrator is not in the database (especially with partial matches; see below).

In recent years, law enforcement has sometimes adopted the strategy of turning this problem on its head and using these familial leads as starting points of investigation as a way to get to the true perpetrator. This is a controversial practice.

Each of the above factors results in an increase in the probability of a match between different individuals. But the effect is small; even after taking them into account, as long as we’re talking about the full 13-locus profile, most individuals do in fact have a unique DNA profile, albeit fewer than would be predicted by the simple entropy calculation.

Unfortunately, crime-scene sample collection is far from perfect, and profiles are often not extracted accurately from the physical samples due to limitations of technology and the quality of the sample. These inaccuracies in a crime-scene profile introduce errors into the matching process, which are the primary reason for false matches in investigations.

Partial and mixed profiles. Sometimes only a “partial profile” can be extracted from a crime-scene DNA sample. This means that only a subset of the 13 genotypes can be measured. This could be because the quantity of DNA available is too small (interfering with the “amplification” process at some of the loci), because the DNA has degraded, or because it is contaminated with chemicals called PCR inhibitors that interfere with the decoding process.

The other type of inaccuracy occurs when the DNA sample collected is in fact a mixture from multiple individuals. If this happens, multiple values for some genotypes might be measured. There is no foolproof way of separating the genotypes of each individual in the mixture.

These are very common occurrences, particularly partial profiles. There are no standards on the quality or quantity of the profile data for the evidence to be admissible in court. Instead, an expert witness computes a “likelihood ratio” based on the specific partial or mixed profile, and presents this to the court. Juries are often left not knowing how to interpret the number they are presented and are vulnerable to the prosecutor’s fallacy.

The birthday paradox. The history of DNA testing is littered with false matches and leads; one reason is the birthday paradox. The number of pairs of individuals in a database of size N grows proportional to N². The FBI database, for instance, has about 200,000 crime-scene profiles and 5 million offender profiles, for a total of a 1 trillion pairs of profiles. Due to use of partial profiles to find matches, the probability of a match between two random profiles is much higher than one in a trillion.

This long but fascinating paper has many hilarious stories of false DNA matches. Laboratory errors such as mixing up labels on the samples and contamination of the sample with the technician’s DNA appear to be depressingly common as well. Here is another story of lab contamination that cost $14 million.

Why only 13 loci? One question that all this raises is that if the use of a small number of loci causes problems when only a partial profile is available, why not use more of the genome, or even all of it?  Research on mini-STRs shows how to better utilize degraded DNA to recover genotypes from beyond the 13 CODIS loci. The cost of whole-genome genotyping has been falling dramatically, and enables even individuals contributing trace amounts of DNA to a mixture to be identified!

One stumbling block seems to be the small quantity of DNA available from crime scenes; whole genome amplification is being developed to address that. But I suspect that the main reason is inertia: forensic protocols, procedures and expertise in DNA profiling have evolved over the last two decades, and it would be costly to make any changes at all. Whatever the reasons, I’m certain that things are going to be very different in a decade or two, because there are millions of bits of entropy in the entire genome, and forensic science currently uses about 54 of them.

Further reading.

• Wikipedia: DNA profiling
• Legal decisions concerning DNA statistics
• DNA Testing: An Introduction for Non-Scientists
• The Potential for Error in Forensic DNA Testing (referenced above, but worth repeating!)

Some months ago, I wrote about the importance of customer service in the life of direct-to-consumer genomic companies. After the post, Pathway Genomics contacted me and said they were excited to speak more openly about their service. They also want to educate the community on genetic testing services and what these test results will and will not tell you. Here is the interview they have recently given to me.

• Pathway Genomics is one of the newest competitors in the DTC genomics market. How do you aim to make a difference?

Quality. Pathway has a wholly owned federal CLIA and California State licensed laboratory. This onsite lab removes any “middle-man” issues. DNA samples are collected in Pathway’s custom-designed DNA collection kits and shipped directly to Pathway’s laboratory in San Diego, California. Genetic testing services, across five different technology platforms (including gene sequencing) are carried out by staff geneticists. Genetic health, lifestyle, and family history data and ancestry data are interpreted using unique algorithms developed by Pathway. Genetic test results are reviewed by medical staff and genetic counselors for accuracy and then reported via our online secure web site. When appropriate, our genetic counselors will contact customers to present and review their data. At any time, customers can contact Pathway’s Genetic Counselors for help understanding their genetic information.

Content. Pathway offers genetic testing services for both health and ancestry. As part of Pathway’s genetic health testing service, customers can learn about their propensity to develop disease, sensitivities to prescription drugs, or carrier status for mutations causing monogenic disorders. In the case of drug responses, Pathway is the market leader and reports on nearly a dozen different drug responses and adverse reactions. This includes clopidogrel (Plavix), statins, oral contraceptives, and certain cancer fighting treatments. This is important information because not all drugs are effective for all people and in some cases can cause adverse reactions.

Price. Genetic tests ordered through traditional medical outlets may be cost prohibitive for consumers. Pathway offers genetic health and ancestry testing services that are easy and affordable, with tests starting at $99. And for less than $350, consumers can access both health (drug response, carrier status, health conditions) and genetic ancestry tests.

• How many Single Nucleotide Polymorphisms do you test and how many of them do you really use for the analysis?

As of today, Pathway reports on 71 health conditions, including tests for health diseases (24), drug responses and adverse reactions (10), and carrier status (37). Pathway shares this number because this is the information we believe helps consumers choose a genetic testing service right for them. Concerning the number of SNPs tested, we do not disclose this information, as we believe this to be competitive in nature and not informative to the consumer until otherwise validated by research.

• You analyze drug responses, among other features. How accurate are these tests? I mean if you tell me I have a variance in my CYP2C9 gene, should I ask my GP to change the level of Coumadin I’ve been prescribed to?

Pathway has taken great effort to validate the accuracy and specificity of all the markers we report. Our standards exceed those required for federal CLIA certification. Therefore, you can be assured that the genotypes you receive from Pathway are highly accurate. That said, if Pathway told you that you had a genetic variation in your CYP2C9 gene that increased your sensitivity to Coumadin (Warfarin), we believe it’s important to share this information with your physician and discuss a personalized treatment plan based on this genetic data.

• I don’t totally understand the concept behind the 100% money back guarantee. If I think my results don’t represent my real genetic background properly (e.g. because my family history predicts something different), I can get my money back?

Ultimately, we want each of our customers to feel confident about the information they receive about their genetic health or ancestry tests. While some people may not “like” what they learn about their genetic information, we want to do our best in serving our customers. Therefore, if for any reason a customer is not happy with their genetic testing service we will offer them 100% money back.

• Please tell us about your plans for the near future? How do you plan to improve the service?

It’s important to continue to educate consumers, physicians, and the genetics community at large about the benefits associated with genetic testing services-specifically, what genetic testing can and can’t tell you. As the research community continues to make discoveries linking genetic variations to complex diseases, drug responses, etc., we will translate this information into an easy to understand format for our customers, thus helping to make personalized medicine a reality.

A few weeks ago, Pauline C. Ng, Sarah S. Murray, Samuel Levy and J. Craig Venter published a quite an interesting piece  in the October 8, 2009 issue of Nature. In this publication, they had really relevant suggestions for Direct-to-consumer genomics companies such as Navigenics or 23andMe. Now, surprisingly, they two giants published an answer together:

Dear Editor:

We read with interest the Opinion piece entitled “An agenda for personalized medicine” in the October 8, 2009 edition of Nature. Our two companies, though commercially distinct with differentiated products, would like to respond to this piece jointly to show our commitment to working together in an open, transparent fashion.

Our companies agree with most of the recommendations Ng and colleagues made.  Without doubt, genotype-based risk prediction for common, multifactorial diseases is still in its infancy.  More work must be done to standardize markers used; to better explain the contribution of genetics to common, complex diseases; and to incorporate common genetic variants into clinical practice.  Each company, however, has a few points of disagreement and/or explanation it feels important to articulate.  These points from each company follow.

And excerpts from their respective answers:

Response by Navigenics:

With regard to the specific recommendations, Navigenics agrees with most of the suggestions.  For example, we agree with the authors that results showing less than average risk should not be a primary point of focus, a viewpoint that has been incorporated into our service offering in a variety of ways.

Response by 23andMe:

We would like to discuss two technical points about the article.  The authors presented these points in a relatively balanced manner but the subtleties have led to misinterpretations in subsequent media coverage.

#23andme #personalgenomics #DTC @samiahurst @portablegenomic

The request is from my favorite bioethicist and thus can’t be ignored:

@OldCola Please don’t tell me you think 23andme is worth spiting for. Or else explain, pleeease…I don’t get it

Let’s start with two disclaimers: