Monthly Archives: July 2017

Genomic infrastructure needs constant upkeep but still falls into disrepair, upkeep or no, if upkeep quality is compromised. In fact, if DNA repairs are poorly executed, they may not only fail to correct the mutations that are due to ordinary wear and tear, they may also introduce additional mutations. These additional mutations, which appear to be an important cause of cancer, have been associated with DNA repairs that are executed under the influence of alcohol. Other adverse influences on DNAs repair crews include sunlight and smoking.

Cancer is mostly caused by changes in the DNA of our cells that occur during our lifetime rather than those that we inherit from our parents. Identifying the causes of these mutations is a difficult challenge because many processes can result in an identical DNA sequence change in a genome.

Regardless, it is possible to determine which mutations may be attributable to impaired DNA repair mechanisms. What is required, say researchers at the Centre for Genomic Regulation (CRG) in Barcelona, is the right kind of inspection.

The researchers decided to focus on clusters of mutations while scrutinizing more than a thousand tumor genomes, meaning that they hunted for mutations that occur close together in the same part of the genome. Such clusters are highly unlikely to happen by chance. Ultimately, the researchers hoped to get a better picture of the mutagenic factors that affect human cells and that might cause cancer.

Details of the researchers work appeared July 27 in the journal Cell, in an article entitled, Clustered Mutation Signatures Reveal that Error-Prone DNA Repair Targets Mutations to Active Genes. This article makes the case that if mutations occur in clusters, as opposed to being sprinkled randomly through the genome, genome inspectors should suspect DNA repair crews of doing shoddy work.

"Clustered mutations are likely to be generated at the same moment in time, so by looking at several neighboring mutations at once, we can have a better understanding of what has damaged the DNA," says Fran Supek, Ph.D., first author of the Cell article, CRG researcher, and group leader and 'Ramon y Cajal' fellow at the Institute for Research in Biomedicine.

Of nine clustered mutation signatures identified from >1,000 tumor genomes, three relate to variable APOBEC activity and three are associated with tobacco smoking, wrote the authors of the Cell article. An additional signature matches the spectrum of translesion DNA polymerase eta (POLH).

In lymphoid cells, these mutations target promoters, consistent with AID-initiated somatic hypermutation. In solid tumors, however, they are associated with UV exposure and alcohol consumption and target the H3K36me3 chromatin of active genes in a mismatch repair (MMR)-dependent manner.

These results revealed new major mutation-causing processes, including an unusual case of DNA repair which should normally safeguard the genome from damage, but is sometimes subverted and starts introducing clustered mutations.

"Our work provides information about new biological mechanisms underlying some types of cancers, asserted Dr. Supek. For example, the main oncogenes involved in melanoma are well-known, but it is not known what causes the exact mutations that activate these genes to cause cancer. While many mutations in melanoma are recognized to be a direct consequence of UV radiation, the origin of mutations affecting the most important oncogenes is still a mystery. We identified a mechanism that has the capacity to cause these oncogenic, cancer-driving mutations in melanoma."

One of these new mutational processes is highly unusual and it is most evident in active genes. These regions are usually protected by DNA repair mechanismsin other words, DNA repair is directed towards the places where it is needed most.

"Our results suggest that exposure to carcinogens, such as high amounts of alcohol, can shift the balance of the DNA repair machinery from a high-fidelity mode to an error-prone mode, causing the mutation rates to shoot up in the most important bits of the genome," explained Ben Lehner, Ph.D., ICREA research professor at the EMBL-CRG Systems Biology Research Unit and principal investigator of the current study. "This error-prone repair generates a large number of mutations overall and is likely to be a major mutation source in human cells."

DNA repair is extremely important because our bodies are constantly renewing their cells which involves copying more than two meters of DNA and errors inevitably get introduced. Moreover, mutagens in the environment like sunlight and tobacco smoke damage DNA and this damage has to be corrected. DNA repair is normally exquisitely accurate, but some types of damage can only be corrected using lower-fidelity "spellcheckers." It is the mistakes made by one of these less accurate spellcheckers that cause many of the mutations seen in different types of tumors, including liver, colon, stomach, esophagus, and lung cancer.

Alcohol is a well-known contributor to many types of cancer, but the reasons for this are surprisingly unclear. The current study suggests that one effect of alcohol, when consumed in large amounts, is to increase the use of low-fidelity DNA repair, thereby increasing the mutation rate in the most important regions of the genome. This finding provides a first glimpse into one mechanism by which alcohol may contribute to cancer risk. High exposure to sunlight seems to have a similar consequence.

As another part of the study the CRG scientists also found that cigarette smoking is associated with several different kinds of clustered mutations, further revealing the details of how smoking results in horrific damage to our DNA.

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DNA Repair Under the Influence May Raise Risk of Cancer - Genetic Engineering & Biotechnology News

July 28, 2017 by Luis Ceze And Karin Strauss, The Conversation The next frontier of data storage: DNA. Credit: ymgerman/Shutterstock.com

Humanity is producing data at an unimaginable rate, to the point that storage technologies can't keep up. Every five years, the amount of data we're producing increases 10-fold, including photos and videos. Not all of it needs to be stored, but manufacturers of data storage aren't making hard drives and flash chips fast enough to hold what we do want to keep. Since we're not going to stop taking pictures and recording movies, we need to develop new ways to save them.

Over millennia, nature has evolved an incredible information storage medium DNA. It evolved to store genetic information, blueprints for building proteins, but DNA can be used for many more purposes than just that. DNA is also much denser than modern storage media: The data on hundreds of thousands of DVDs could fit inside a matchbox-size package of DNA. DNA is also much more durable lasting thousands of years than today's hard drives, which may last years or decades. And while hard drive formats and connection standards become obsolete, DNA never will, at least so long as there's life.

The idea of storing digital data in DNA is several decades old, but recent work from Harvard and the European Bioinformatics Institute showed that progress in modern DNA manipulation methods could make it both possible and practical today. Many research groups, including at the ETH Zurich, the University of Illinois at Urbana-Champaign and Columbia University are working on this problem. Our own group at the University of Washington and Microsoft holds the world record for the amount of data successfully stored in and retrieved from DNA 200 megabytes.

Preparing bits to become atoms

Traditional media like hard drives, thumb drives or DVDs store digital data by changing either the magnetic, electrical or optical properties of a material to store 0s and 1s.

To store data in DNA, the concept is the same, but the process is different. DNA molecules are long sequences of smaller molecules, called nucleotides adenine, cytosine, thymine and guanine, usually designated as A, C, T and G. Rather than creating sequences of 0s and 1s, as in electronic media, DNA storage uses sequences of the nucleotides.

There are several ways to do this, but the general idea is to assign digital data patterns to DNA nucleotides. For instance, 00 could be equivalent to A, 01 to C, 10 to T and 11 to G. To store a picture, for example, we start with its encoding as a digital file, like a JPEG. That file is, in essence, a long string of 0s and 1s. Let's say the first eight bits of the file are 01111000; we break them into pairs 01 11 10 00 which correspond to C-G-T-A. That's the order in which we join the nucleotides to form a DNA strand.

Digital computer files can be quite large even terabytes in size for large databases. But individual DNA strands have to be much shorter holding only about 20 bytes each. That's because the longer a DNA strand is, the harder it is to build chemically.

So we need to break the data into smaller chunks, and add to each an indicator of where in the sequence it falls. When it's time to read the DNA-stored information, that indicator will ensure all the chunks of data stay in their proper order.

Now we have a plan for how to store the data. Next we have to actually do it.

Storing the data

After determining what order the letters should go in, the DNA sequences are manufactured letter by letter with chemical reactions. These reactions are driven by equipment that takes in bottles of A's, C's, G's and T's and mixes them in a liquid solution with other chemicals to control the reactions that specify the order of the physical DNA strands.

This process brings us another benefit of DNA storage: backup copies. Rather than making one strand at a time, the chemical reactions make many identical strands at once, before going on to make many copies of the next strand in the series.

Once the DNA strands are created, we need to protect them against damage from humidity and light. So we dry them out and put them in a container that keeps them cold and blocks water and light.

But stored data are useful only if we can retrieve them later.

Reading the data back

To read the data back out of storage, we use a sequencing machine exactly like those used for analysis of genomic DNA in cells. This identifies the molecules, generating a letter sequence per molecule, which we then decode into a binary sequence of 0s and 1s in order. This process can destroy the DNA as it is read but that's where those backup copies come into play: There are many copies of each sequence.

And if the backup copies get depleted, it is easy to make duplicate copies to refill the storage just as nature copies DNA all the time.

At the moment, most DNA retrieval systems require reading all of the information stored in a particular container, even if we want only a small amount of it. This is like reading an entire hard drive's worth of information just to find one email message. We have developed techniques based on well-studied biochemistry methods that let us identify and read only the specific pieces of information a user needs to retrieve from DNA storage.

Remaining challenges

At present, DNA storage is experimental. Before it becomes commonplace, it needs to be completely automated, and the processes of both building DNA and reading it must be improved. They are both prone to error and relatively slow. For example, today's DNA synthesis lets us write a few hundred bytes per second; a modern hard drive can write hundreds of millions of bytes per second. An average iPhone photo would take several hours to store in DNA, though it takes less than a second to save on the phone or transfer to a computer.

These are significant challenges, but we are optimistic because all the relevant technologies are improving rapidly. Further, DNA data storage doesn't need the perfect accuracy that biology requires, so researchers are likely to find even cheaper and faster ways to store information in nature's oldest data storage system.

Explore further: Researchers break record for DNA data storage

This article was originally published on The Conversation. Read the original article.

University of Washington and Microsoft researchers have broken what they believe is the world record for the amount of digital data successfully storedand retrievedin DNA molecules.

(Phys.org) -- A team of researchers in the US has successfully encoded a 5.27 megabit book using DNA microchips, and they then read the book using DNA sequencing. Their experiments show that DNA could be used for long-term ...

Humanity may soon generate more data than hard drives or magnetic tape can handle, a problem that has scientists turning to nature's age-old solution for information-storageDNA.

Hand-written letters and printed photos seem quaint in today's digital age. But there's one thing that traditional media have over hard drives: longevity. To address this modern shortcoming, scientists are turning to DNA ...

Technology companies routinely build sprawling data centers to store all the baby pictures, financial transactions, funny cat videos and email messages its users hoard.

We are producing more data than ever before, with more than 2.5 quintillion bytes produced every day, according to computer giant IBM. That's a staggering 2,500,000,000,000 gigabytes of data and it's growing fast.

(Phys.org)Researchers have designed an optical lens that exhibits two properties that so far have not been demonstrated together: self-focusing and an optical effect called the Talbot effect that creates repeating patterns ...

Researchers have taken an important step toward the long-sought goal of a quantum computer, which in theory should be capable of vastly faster computations than conventional computers, for certain kinds of problems. The new ...

Washington State University physicists have found a way to write an electrical circuit into a crystal, opening up the possibility of transparent, three-dimensional electronics that, like an Etch A Sketch, can be erased and ...

Researchers at the UAB have come up with a method to measure the strength of the superposition coherence in any given quantum state. The method, published in the journal Proceedings of the Royal Society A, is based on the ...

The inner workings of the human brain have always been a subject of great interest. Unfortunately, it is fairly difficult to view brain structures or intricate tissues due to the fact that the skull is not transparent by ...

The perfect performance of superconductors could revolutionize everything from grid-scale power infrastructure to consumer electronics, if only they could be coerced into operating above frigid temperatures. Even so-called ...

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Storing data in DNA brings nature into the digital universe - Phys.Org

(The Conversation is an independent and nonprofit source of news, analysis and commentary from academic experts.)

Luis Ceze, University of Washington and Karin Strauss, University of Washington

(THE CONVERSATION) Humanity is producing data at an unimaginable rate, to the point that storage technologies cant keep up. Every five years, the amount of data were producing increases 10-fold, including photos and videos. Not all of it needs to be stored, but manufacturers of data storage arent making hard drives and flash chips fast enough to hold what we do want to keep. Since were not going to stop taking pictures and recording movies, we need to develop new ways to save them.

Over millennia, nature has evolved an incredible information storage medium DNA. It evolved to store genetic information, blueprints for building proteins, but DNA can be used for many more purposes than just that. DNA is also much denser than modern storage media: The data on hundreds of thousands of DVDs could fit inside a matchbox-size package of DNA. DNA is also much more durable lasting thousands of years than todays hard drives, which may last years or decades. And while hard drive formats and connection standards become obsolete, DNA never will, at least so long as theres life.

The idea of storing digital data in DNA is several decades old, but recent work from Harvard and the European Bioinformatics Institute showed that progress in modern DNA manipulation methods could make it both possible and practical today. Many research groups, including at the ETH Zurich, the University of Illinois at Urbana-Champaign and Columbia University are working on this problem. Our own group at the University of Washington and Microsoft holds the world record for the amount of data successfully stored in and retrieved from DNA 200 megabytes.

Traditional media like hard drives, thumb drives or DVDs store digital data by changing either the magnetic, electrical or optical properties of a material to store 0s and 1s.

To store data in DNA, the concept is the same, but the process is different. DNA molecules are long sequences of smaller molecules, called nucleotides adenine, cytosine, thymine and guanine, usually designated as A, C, T and G. Rather than creating sequences of 0s and 1s, as in electronic media, DNA storage uses sequences of the nucleotides.

There are several ways to do this, but the general idea is to assign digital data patterns to DNA nucleotides. For instance, 00 could be equivalent to A, 01 to C, 10 to T and 11 to G. To store a picture, for example, we start with its encoding as a digital file, like a JPEG. That file is, in essence, a long string of 0s and 1s. Lets say the first eight bits of the file are 01111000; we break them into pairs 01 11 10 00 which correspond to C-G-T-A. Thats the order in which we join the nucleotides to form a DNA strand.

Digital computer files can be quite large even terabytes in size for large databases. But individual DNA strands have to be much shorter holding only about 20 bytes each. Thats because the longer a DNA strand is, the harder it is to build chemically.

So we need to break the data into smaller chunks, and add to each an indicator of where in the sequence it falls. When its time to read the DNA-stored information, that indicator will ensure all the chunks of data stay in their proper order.

Now we have a plan for how to store the data. Next we have to actually do it.

After determining what order the letters should go in, the DNA sequences are manufactured letter by letter with chemical reactions. These reactions are driven by equipment that takes in bottles of As, Cs, Gs and Ts and mixes them in a liquid solution with other chemicals to control the reactions that specify the order of the physical DNA strands.

This process brings us another benefit of DNA storage: backup copies. Rather than making one strand at a time, the chemical reactions make many identical strands at once, before going on to make many copies of the next strand in the series.

Once the DNA strands are created, we need to protect them against damage from humidity and light. So we dry them out and put them in a container that keeps them cold and blocks water and light.

But stored data are useful only if we can retrieve them later.

To read the data back out of storage, we use a sequencing machine exactly like those used for analysis of genomic DNA in cells. This identifies the molecules, generating a letter sequence per molecule, which we then decode into a binary sequence of 0s and 1s in order. This process can destroy the DNA as it is read but thats where those backup copies come into play: There are many copies of each sequence.

And if the backup copies get depleted, it is easy to make duplicate copies to refill the storage just as nature copies DNA all the time.

At the moment, most DNA retrieval systems require reading all of the information stored in a particular container, even if we want only a small amount of it. This is like reading an entire hard drives worth of information just to find one email message. We have developed techniques based on well-studied biochemistry methods that let us identify and read only the specific pieces of information a user needs to retrieve from DNA storage.

At present, DNA storage is experimental. Before it becomes commonplace, it needs to be completely automated, and the processes of both building DNA and reading it must be improved. They are both prone to error and relatively slow. For example, todays DNA synthesis lets us write a few hundred bytes per second; a modern hard drive can write hundreds of millions of bytes per second. An average iPhone photo would take several hours to store in DNA, though it takes less than a second to save on the phone or transfer to a computer.

These are significant challenges, but we are optimistic because all the relevant technologies are improving rapidly. Further, DNA data storage doesnt need the perfect accuracy that biology requires, so researchers are likely to find even cheaper and faster ways to store information in natures oldest data storage system.

This article was originally published on The Conversation. Read the original article here: http://theconversation.com/storing-data-in-dna-brings-nature-into-the-digital-universe-78226.

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Storing data in DNA brings nature into the digital universe - San ... - San Francisco Chronicle