Rapid gene machines used to find cause of newborn illnesses

U.S. scientists have sequenced the entire genetic code of four gravely ill newborns and identified genetic diseases in three of them in two days, quick enough to help doctors make treatment decisions.

Doctors behind the preliminary study released on Wednesday say it demonstrates a practical use for whole genome sequencing, in which researchers analyze all 3.2 billion chemical "bases" or "letters" that make up the human genetic code.

"It is now feasible to decode an entire genome and provide interim results back to the physician in two days," said Dr. Stephen Kingsmore, director of the Center for Pediatric Genomic Medicine at Children's Mercy medical center in Kansas City, Missouri, whose study was published in the journal Science Translational Medicine.

The study tested two software programs developed at Children's Mercy that were used in conjunction with a high-speed gene sequencer from Illumina called HiSeq 2500, which can sequence an entire genome in about 25 hours.

The company helped pay for the study and company researchers took part in it.

Next-generation gene sequencing machines have driven down the cost of whole genome sequencing, but making practical use of the data has been more challenging, largely because of the time it takes to analyze all of the data.

As many as a third of babies admitted to a neonatal intensive care unit in the United States have some form of genetic disease. Treatments are currently available for more than 500 diseases, but identifying them quickly has been a problem.

Typically, genetic testing on newborns using conventional methods takes four to six weeks, long enough that the infant has either died or been sent home.

"Up until now, they have really had to practice medicine blindfolded," Kingsmore said in a telephone briefing with reporters.

Dr. Neil Miller, director of informatics at Children's Mercy, said the software programs help doctors identify which genes to test, and analyze the data quickly.

One of these programs, called SSAGA, allows doctors to order this test based on the child's symptoms, without having to know in advance which genes to test for.

The software only maps genes associated with the child's symptoms. SSAGA does this for nearly 600 diseases, but the team is expanding this to include all 3,500 known disease genes, Miller told the briefing.

The team developed a second software program called Runes that helps determine which of the suspected genes was most likely to be the cause of the child's illness.

In the study, the team tested the system on four seriously ill babies whose conditions were suspected of having a genetic cause. Only one of the infants is still alive, a boy born with a rare heart defect that the team discovered is also shared by the child's 6-year-old brother. The infant underwent heart surgery.

The testing also was able to diagnose a rare form of epilepsy in a baby girl, and identify the likely cause of a rare and lethal skin condition in a baby boy, which arose from a new genetic mutation that was not passed down from either parent. The team was unable to find out what caused another boy's heart defect.

"We basically struck out completely, for now anyway," said Dr. Carol Saunders, clinical lab director at the hospital who helped interpreted the study results.

Even though the study did not provide cures for the babies, she said, it could give parents more information about the cause of their child's illness and allow them to make decisions about what kinds of treatments they wanted to pursue.

The test is projected to cost $13,500, but the team believes that may be worth it given the high cost of care in a neonatal intensive care unit, which runs roughly $8,000 per night.

The next move is to broaden the test to include 100 or more babies to determine the benefits, costs and potential problems linked with the testing.

Because the Illumina machine was not available in the United States, the team had to discount the time it took to ship the blood samples to Britain, where the actual sequencing was done.

But Kingsmore said the hospital expects to receive its own HiSeq 2500 machine next month. Eventually, the hospital hopes to have its testing validated, so the researchers can do genetic testing on newborns in hospitals across the United States.

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Switching cause and effect in quantum world? A causes B causes A

One of the most deeply rooted concepts in science and in our everyday life is causality; the idea that events in the present are caused by events in the past and, in turn, act as causes for what happens in the future. If an event A is a cause of an effect B, then B cannot be a cause of A. Now theoretical physicists from the University of Vienna and the Université Libre de Bruxelles have shown that in quantum mechanics it is possible to conceive situations in which a single event can be both, a cause and an effect of another one.The findings will be published this week in Nature Communications.Although it is still not known if such situations can be actually found in nature, the sheer possibility that they could exist may have far-reaching implications for the foundations of quantum mechanics, quantum gravity and quantum computing.Causal relations: who influences whomIn everyday life and in classical physics, events are ordered in time: a cause can only influence an effect in its future not in its past. As a simple example, imagine a person, Alice, walking into a room and finding there a piece of paper. After reading what is written on the paper Alice erases the message and leaves her own message on the piece of paper. Another person, Bob, walks into the same room at some other time and does the same: he reads, erases and re-writes some message on the paper. If Bob enters the room after Alice, he will be able to read what she wrote; however Alice will not have a chance to know Bob's message. In this case, Alice's writing is the "cause" and what Bob reads the "effect." Each time the two repeat the procedure, only one will be able to read what the other wrote. Even if they don't have watches and don't know who enters the room first, they can deduce it by what they write and read on the paper. For example, Alice might write "Alice was here today," such that if Bob reads the message, he will know that he came to the room after her.Quantum violation of causal orderAs long as only the laws of classical physics are allowed, the order of events is fixed: either Bob or Alice is first to enter the room and leave a message for the other person. When quantum mechanics enters into play, however, the picture may change drastically. According to quantum mechanics, objects can lose their well-defined classical properties, such as e.g. a particle that can be at two different locations at the same time. In quantum physics this is called a "superposition."Now an international team of physicists led by Caslav Brukner from the University of Vienna have shown that even the causal order of events could be in such a superposition. If -- in our example -- Alice and Bob have a quantum system instead of an ordinary piece of paper to write their messages on, they can end up in a situation where each of them can read a part of the message written by the other. Effectively, one has a superposition of two situations: "Alice enters the room first and leaves a message before Bob" and "Bob enters the room first and leaves a message before Alice.""Such a superposition, however, has not been considered in the standard formulation of quantum mechanics since the theory always assumes a definite causal order between events," says Ognyan Oreshkov from the Université Libre de Bruxelles (formerly University of Vienna). "But if we believe that quantum mechanics governs all phenomena, it is natural to expect that the order of events could also be indefinite, similarly to the location of a particle or its velocity," adds Fabio Costa from the University of Vienna.The work provides an important step towards understanding that definite causal order might not be a mandatory property of nature. "The real challenge is finding out where in nature we should look for superpositions of causal orders," explains Caslav Brukner from the Quantum Optics, Quantum Nanophysics, Quantum Information group of the University of Vienna.View the original article here

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