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Scooped by Dr. Stefan Gruenwald!

“Zombie” HIV RNA might cause ongoing damage

“Zombie” HIV RNA might cause ongoing damage | Amazing Science |

When HIV infects a cell, it inserts its own DNA into the host’s chromosomes. In people whose disease is well-controlled by medication, the majority of affected cells contain a busted HIV genome, with mutations or deletions, that can’t make any more viruses. These have been considered “junk” by most scientists, says study author Hiromi Imamichi, a virologist at NIAID. Imamichi thinks they’re more like “zombies”—dead, but still able to do damage.


Using blood samples from a repository at the National Institutes of Health Clinical Center in Bethesda, Imamichi checked for HIV DNA and RNA in cells from nine patients. For people whose disease was poorly controlled, with plenty of detectable virus in their blood, most of the HIV genomes in their cells were intact. But in those whose disease was well-managed, most of the HIV genomes were shortened due to missing pieces. Nonetheless, even in the people with HIV under control, their cells were producing defective RNAs from the truncated HIV genomes. Though flawed, those RNAs contained sequences that could, theoretically, be used to make protein. For example, in some cases different HIV genes were glued together, potentially encoding chimeric proteins.


The authors provide “quite convincing evidence” that cells with defective HIV genomes make HIV RNA, says Mathias Lichterfeld, a translational immunologist and infectious disease physician at Brigham and Women’s Hospital in Boston, who was not involved in the study. What remains to be shown is whether those RNAs do then make warped, mismatched HIV proteins. It wasn’t possible to find such proteins in the blood samples, since any amount made by the small cell populations would be undetectable, Lane says. But he and Imamichi are now trying to prove defective HIV genomes make protein both in vitro and in vivo.


If those proteins do exist, Lane believes “they’re probably causing some kind of immune activation.” That would explain why even in people whose HIV is kept in check, antibodies to HIV proteins and inflammation persist. The defective proteins might “distract” the immune system from the truly dangerous viruses, Lichterfeld speculates. The authors plan to study whether the presence of defective HIV RNAs correlates with higher immune activity in patients.


Lichterfeld thinks it might be possible to block production of the defective HIV RNAs. Knocking out these zombies would likely improve the outlook for patients, by eliminating a cause for inflammation, Lichterfeld says, and Lane suspects such a therapeutic could be a key piece of an eventual cure.

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Kataegis, gene Mutation “Hotspots” Linked to Better Breast Cancer Outcomes

Kataegis, gene Mutation “Hotspots” Linked to Better Breast Cancer Outcomes | Amazing Science |

Kataegis is a recently discovered phenomenon in which multiple mutations cluster in a few hotspots in a genome. The anomaly was previously found in some cancers, but it has been unclear what role kataegis plays in tumor development and patient outcomes. Using a database of human tumor genomic data, researchers at the University of California San Diego School of Medicine and Moores Cancer Center have discovered that kataegis is actually a positive marker in breast cancer — patients with these mutation hotspots have less invasive tumors and better prognoses.


The study, published June 30 in Cell Reports, also suggests kataegis status could help doctors determine the treatment options that might work best for patients with the mutation pattern. “We don’t know what causes kataegis, and before this study not much was known about its functional importance at the molecular or clinical level,” said senior author Kelly Frazer, PhD, professor of pediatrics and director of the Institute for Genomic Medicine at UC San Diego School of Medicine and Moores Cancer Center. “We’ve now found that kataegis is associated with a good prognosis for patients with breast cancer.”


Kataegis occurs in approximately 55 percent of breast cancers. To determine the role of this phenomenon in patient outcomes, Frazer and her team studied human breast cancer data available from The Cancer Genome Atlas (TCGA), the National Institutes of Health’s database of genomic information from more than 15,000 human tumors representing many cancer types. The Frazer team established the kataegis status of 97 breast tumors and then paired this information with patient data, such as age at diagnosis, treatment and outcome. They also looked at an additional 412 human breast cancers for which they predicted kataegis status.


The researchers found several different clinical factors associated with kataegis. These mutation hotspots were more common in breast cancer patients diagnosed at a later age, and patients with HER2-positive and high-grade tumors.

What’s more, the presence of kataegis was a marker for good prognosis. Kataegis on chromosome 17 and 22 in particular were associated with low tumor invasiveness. And finally, although causes of death for patients in the TCGA database are not known, patients without kataegis tended to die younger (median age 47 years old) than patients with kataegis (median age 78 years old).


In a finding that helps explain kataegis’ beneficial effect, the researchers noted that genes located near kataegis hotspots were less likely to behave abnormally than genes located further away in the genome. 

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Tweaked deep sequencing technique allows for profiling microRNA

Tweaked deep sequencing technique allows for profiling microRNA | Amazing Science |

MicroRNA (miRNA) are cellular fragments of RNA that in some organisms prevent the production of certain proteins. They have been found to be expressed in tissues of some non-mammals and in some embryos prior to pre-implantation. Little is known about their function in mammals, however, though prior research had found them to exist in oocytes (ovarian cells that lead to the development of an ovum) and early embryos. Prior efforts to deep sequence them in mammals has proved to be extremely challenging due to the numbers of them that must be processed, thus scientists still do not know what role they may play in embryo development, if any. In this new effort, the researchers report that they have found a way to tweak the cDNA library construction method for small RNAs resulting in a need for only 10 nanograms of RNA for doing a deep sequence, and because of that, were able to profile samples of both mouse oocytes and early embryos.


To tweak the construction method, the researchers optimized the 5' and 3' adaptor ligation and PCR amplification steps, which allowed for drastically reducing the amount of RNA needed. To test their ideas they performed the tweaking on 293 human embryonic kidney cells. Once they had the technique developed, they switched to testing mice oocytes and early embryos to learn more about the role of miRNA in mammal embryo development. They report that they were able to trace the processes surrounding miRNA as it moved from fertilization to early embryonic development—which was the first time that had ever been done. Furthermore, they found that the role miRNA played was suppressed as initial cell division was occurring—though it was not clear why that occurred—but later it was reactivated, perhaps as part of the process of regulating zygotic genetic growth factors.

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How Neanderthal DNA Helps Humanity: A Map of Ancient Genes

How Neanderthal DNA Helps Humanity: A Map of Ancient Genes | Amazing Science |

Neanderthals and Denisovans would have been a good source of helpful DNA for our ancestors. They had lived in Europe and Asia for hundreds of thousands of years — enough time to adjust to the cold climate, weak sun and local microbes. “What better way to quickly adapt than to pick up a gene variant from a population that had probably already been there for 300,000 years?” Akey said. Indeed, the Neanderthal and Denisovan genes with the greatest signs of selection in the modern human genome “largely have to do with how humans interact with the environment,” he said.


To find these adaptive segments, scientists search the genomes of contemporary humans for regions of archaic DNA that are either more common or longer than expected. Over time, useless pieces of Neanderthal DNA — those that don’t help the carrier — are likely to be lost. And long sections of archaic DNA are likely to be split into smaller segments unless there is selective pressure to keep them intact.


In 2014, two groups, one led by Akey and the other by David Reich, a geneticist at Harvard Medical School, independently published genetic maps that charted where in our genomes Neanderthal DNA is most likely to be found. To Akey’s surprise, both maps found that the most common adaptive Neanderthal-derived genes are those linked to skin and hair growth. One of the most striking examples is a gene called BNC2, which is linked to skin pigmentation and freckling in Europeans. Nearly 70 percent of Europeans carry the Neanderthal version.


Scientists surmise that BNC2 and other skin genes helped modern humans adapt to northern climates, but it’s not clear exactly how. Skin can have many functions, any one of which might have been helpful. “Maybe skin pigmentation, or wound healing, or pathogen defense, or how much water loss you have in an environment, making you more or less susceptible to dehydration,” Akey said. “So many potential things could be driving this — we don’t know what differences were most important.”

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Gene editing creates hornless cattle

Gene editing creates hornless cattle | Amazing Science |
Alison L. Van Eenennaam, PhD, a geneticist and cooperative extension specialist also at UC-Davis, is working with the Minnesota-based company Recombinetics on, among other things, a project that has produced some of the Holstein dairy cattle that lack horns by editing one allele to match another found in Angus cattle.

“We’ve still got a dairy cow with all the good dairy genetics,” she said. “We’ve just gone in and tweaked a little snippet of DNA at the gene that makes horns and made it so it’s the variant for Angus, which doesn’t grow horns.”
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The race to create super-crops

The race to create super-crops | Amazing Science |
Old-fashioned breeding techniques are bearing more fruit than genetic engineering in developing hyper-efficient plants.


Big corporations such as DuPont Pioneer in Johnston, Iowa, have spent more than a decadedeveloping improved crops through genetic engineering, and some companies say that their transgenic varieties look promising in field trials. But there are still no fertilizer-frugal transgenic crops on the market, and several agricultural organizations around the globe are reviewing their biotechnology initiatives in this area.


Plant biologist Allen Good of the University of Alberta in Edmonton, Canada, spent years working with companies to develop genetically modified (GM) crops that require little fertilizer, but he says that this approach has not been as fruitful as conventional techniques. The problem is that there are so many genes involved in nutrient uptake and use — and environmental variations alter how they are expressed.


“Nutrient efficiency was supposed to be one of those traits with broad applicability that could make companies lots of money. But they haven't developed the way we thought,” says Good.


Despite the scientific and breeding challenges, some researchers say that all strategies must be explored to develop crops that are less nutrient needy. With the global population heading towards 10 billion people by 2050, frugal crops could be essential to feed the planet. “There is a huge worldwide potential for these traits to help increase food production and sustainable development,” says Matin Qaim, an agricultural economist at the University of Göttingen in Germany.

Via Meristemi
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Shedding light on the 'dark matter' of the genome

Shedding light on the 'dark matter' of the genome | Amazing Science |

What used to be dismissed by many as "junk DNA" is back with a vengeance as growing data points to the importance of non-coding RNAs (ncRNAs)—genome's messages that do not code for proteins—in development and disease formation. But our progress in understanding these molecules has been slow because of the lack of technologies that allow the systematic mapping of their functions.


Now, Professor Benjamin Blencowe's team at the University of Toronto's Donnelly Centre, including lead authors Eesha Sharma and Tim Sterne-Weiler, have developed a method, described in May 19, 2016 issue of Molecular Cell, that enables scientists to explore in depth what ncRNAs do in human cells. The study is published on the same day with two other papers in Molecular Cell and Cell, respectively, from Dr. Yue Wan's group at the Genome Institute of Singapore and Dr. Howard Chang's group at Stanford University in California, who developed similar methods to study RNAs in different organisms.


Of the 3 billion letters in the human genome, only two per cent make up the protein-coding genes. The genes are copied, or transcribed, into messenger RNA (mRNA) molecules, which provide templates for building proteins that do most of the work in the cell. Much of the remaining 98 per cent of the genome was initially considered by some as lacking in functional importance. However, large swaths of the non coding genome—between half and three quarters of it—are also copied into RNA.


What the resulting ncRNAs might do depends on whom you ask. Some researchers believe that most ncRNAs have no function, that they are just a by-product of the genome's powerful transcription machinery that makes mRNA. However, it is emerging that many ncRNAs have important roles in gene regulation. This view is supported in that some ncRNAs act as carriages for shuttling the mRNAs around the cell, or provide a scaffold for other proteins and RNAs to attach to and do their jobs.


But the majority of available data has trickled in piecemeal or through serendipitous discovery. And with emerging evidence that ncRNAs could drive disease progression, such as cancer metastasis, there was a great need for a technology that would allow a systematic functional analysis of ncRNAs.


"Up until now, with existing methods, you had to know what you are looking for because they all require you to have some information about the RNA of interest. The power of our method is that you don't need to preselect your candidates, you can see what's occurring globally in cells, and use that information to look at interesting things we have not seen before and how they are affecting biology," says Eesha Sharma, a PhD candidate in Blencowe's group who, along with postdoctoral fellow Tim Sterne-Weiler, co-developed the method.


The new tool, called 'LIGR-Seq', captures interactions between different RNA molecules. When two RNA molecules have matching sequences - strings of letters copied from the DNA blueprint - they will stick together like Velcro. The paired RNA structures are then removed from cells and analyzed by state-of-the-art sequencing methods to precisely identify the RNAs that are stuck together. "Most researchers in the life sciences agree that there's an urgent need to understand what ncRNAs do. This technology will open the door to developing a new understanding of ncRNA function," says Blencowe, who is also a professor in the Department of Molecular Genetics.


Not having to rely on pre-existing knowledge is one strength of the method that will boost the discovery of RNA pairs that have never been seen before. The other is that scientists can for the first time look at RNA interactions as they occur in living cells, in all their complexity, unlike in the juices of mashed up cells that they had to rely on before. This is a bit like moving on to explore marine biology from collecting shells on the beach to scuba-diving among the coral reefs where the scope for discovery is so much bigger.

ncRNAs come in multiple flavours: there's rRNA, tRNA, snRNA, snoRNA, piRNA, miRNA, and lncRNA, to name a few, where prefixes reflect the RNA's place in the cell or some aspect of its function. But the truth is that no one really knows the extent to which these ncRNAs control what goes on in the cell, nor how they do this. The new technology developed by Blencowe's group has been able to pick up new interactions involving all classes of RNAs and has already revealed some unexpected findings.

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The gene hunters 

The gene hunters  | Amazing Science |

Criss-crossing the globe on a quest for unusual DNA, researchers have discovered a rare mutation that promises insights into both epilepsy and autism — and points to a treatment.

Via Integrated DNA Technologies
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History of road-tripping shaped dromedar's DNA

History of road-tripping shaped dromedar's DNA | Amazing Science |
Centuries of caravan domestication and travel left some metaphorical tire marks on Arabian camel genes, researchers find.


Arabian camels (Camelus dromedarius) have trekked across ancient caravan routes in Asia and Africa for 3,000 years. But it’s unclear how camels’ domestication has affected their genetic blueprints.


To find out, Faisal Almathen of King Faisal University in Saudi Arabia and his colleagues combed through the DNA of 1,083 modern camels and ancient remains of wild and domesticated camels found at archaeological sites going back to 5000 B.C.


Camels run high on genetic diversity thanks to periodic restocking from now-extinct wild populations in the centuries after their domestication, the team reports May 9 in the Proceedings of the National Academy of Sciences. Travel on human caravan routes also created a steady flow of genes between different domesticated populations, except in a geographically isolated group in East Africa. That diversity may give some camel populations a leg up in adapting to future changes in climate, the authors suggest. 

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Why are carrots orange? Genome sequencing gives clues

Why are carrots orange? Genome sequencing gives clues | Amazing Science |
The humble supermarket carrot owes its deep orange colour to a newly-found gene, according to an analysis of the full carrot genome.


Carrots are members of the Apiaceae family of plants, which include celery, parsley, fennel, coriander, dill and parsnip. They are related to crops in the sunflower, artichoke and lettuce — the latter which it split from about 72 million years ago. Historically, carrots had small white roots with a woody interior. They most likely came from areas of Iran and Afghanistan, where they still grow today.


Initially they were grown for their aromatic leaves, but over hundreds of years farmers turned a naturally occurring subspecies of the carrot into a larger, less woody root. Domesticated yellow and purple carrots were found in Central Asia around 1,000 years ago, and an orange version emerged in late 16th century Holland, most probably from crossing yellow carrots with purple ones.


By using NGS technologies, researchers sequenced the genomes of 35 different carrot specimens and subspecies, both wild and cultivated, in an attempt to understand how carrots evolved into those we find in our fridge. They found a gene responsible for the high concentration of beta-carotene in the orange carrot taproot. They also identified more than 32,000 genes in a typical orange carrot.


The genome could help breed carrots that have high levels of beta-carotene and are pest resistant.

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Scientists Want To Sequence The Genome Of Leonardo Da Vinci

Scientists Want To Sequence The Genome Of Leonardo Da Vinci | Amazing Science |

Five hundred years ago, Leonardo da Vinci was pioneering pretty much every field of study going, from poetry to mathematics, engineering, anatomy, science, astronomy, and geology. He wasn’t bad at painting either, apparently. Seemingly inspired by his feverishly creative spirit, scientists have hatched a mad plan to sequence his genome and attempt to piece together his incredible life.


The Leonardo Project is bringing together a wealth of scientists, historians, archeologists and art experts from universities around the world. They have recently outlined a few of their plans in a special edition of the Human Evolution journal.


The team is going to look for traces of DNA and fingerprints on his books, notepads, paintings, and equipment. They then hope to pair this with information from the hair, bones, fingerprints, and skin cells of his known past and present relatives. As you can imagine, this is no small feat. Much of the work will include tracking the history and final resting place of Leonardo’s family from the 14th century right up to now.


Rhonda Roby, a geneticist on the project, spoke to Gizmodo about some of the challenges in finding the physical remnants of Da Vinci, saying: “More and more techniques are being developed to recover DNA from people touching things.” “I also think there’s a possibility of biological material inside paintings,” she added. “The challenge would be actually getting that material out without damaging the artwork.”


The legacy of Da VInci’s work in science, engineering, and culture is nothing short of superhuman. But despite this, very little is known about the man himself. One of the things that will be revealed from this genome sequencing is the appearance of the Renaissance polymath. By fitting together bits of the genetic jigsaw, they’ll be able to get a fair idea of his eye color, skin tone, hair color, weight, height, and face shape. They also reckon they’ll be able to get a fair idea of his diet, his health, and his personality.


There’re no plans to clone the great polymath just yet, though.

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Skeletal stem cells form the blueprint of the face structure

Skeletal stem cells form the blueprint of the face structure | Amazing Science |

Timing is everything when it comes to the development of the vertebrate face. In a new study published in PLoS Genetics, USC Stem Cell researcher Lindsey Barske from the laboratory of Gage Crump and her colleagues identify the roles of key molecular signals that control this critical timing.


Previous work from the Crump and other labs demonstrated that two types of molecular signals, called Jagged-Notch and Endothelin1 (Edn1), are critical for shaping the face. Loss of these signals results in facial deformities in both zebrafish and humans, revealing these as essential for patterning the faces of all vertebrates.


Using sophisticated genetic, genomic and imaging tools to study zebrafish, the researchers discovered that Jagged-Notch and Edn1 work in tandem to control where and when stem cells turn into facial cartilage. In the lower face, Edn1 signals accelerate cartilage formation early in development. In the upper face, Jagged-Notch signals prevent stem cells from making cartilage until later in development. The authors found that these differences in the timing of stem cells turning into cartilage play a major role in making the upper and lower regions of the face distinct from one another.


"We've shown that the earliest blueprint of the facial skeleton is set up by spatially intersecting signals that control when stem cells turn into cartilage or bone. Logically, therefore, small shifts in the levels of these signals throughout evolution could account for much of the diversity of shapes we see within the skulls of different animals, as well as the wonderful array of facial shapes seen in humans," said Barske, lead author and A.P. Giannini postdoctoral research fellow.

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Genomics for the masses: AstraZeneca launches project to sequence 2 million genomes

Genomics for the masses: AstraZeneca launches project to sequence 2 million genomes | Amazing Science |
Drug company aims to pool genomic and medical data in hunt for rare genetic sequences associated with disease.


One of the world’s largest pharmaceutical companies has launched a massive effort to compile genome sequences and health records from two million people over the next decade. In doing so, AstraZeneca and its collaborators hope to unearth rare genetic sequences that are associated with disease and with responses to treatment.


It’s an unprecedented number of participants for this type of study, says Ruth March, vice-president and head of personalized health care and biomarkers at AstraZeneca, which is headquartered in London. “That’s necessary because we’re going to be looking for very rare differences among individuals.”


To achieve that ambitious goal, AstraZeneca will partner with research institutions including the Wellcome Trust Sanger Institute in Hinxton, UK, and Human Longevity, a biotechnology company founded in San Diego, California, by genomics pioneer Craig Venter. AstraZeneca also expects to draw on data from 500,000 participants in its own clinical trials, and medical samples that it has accrued over the past 15 years.


In doing so, AstraZeneca will be following a burgeoning trend in genetics research. For years, geneticists pursued common variations in human DNA sequences that are linked to complex diseases such as diabetes and heart disease. The approach yielded some important insights, but these common variations often accounted for only a small percentage of the genetic contribution to individual diseases.


Researchers are now increasingly focusing on the contribution of unusual genetic variants to disease. Combinations of these variants can hold the key to an individual's traits, says Venter.


The hunt for important rare variants has led AstraZeneca to partner with the Institute for Molecular Medicine Finland, says Aarno Palotie, who heads the Human Genomics Program there. Finland’s population was geographically isolated until recently, he notes, which makes for a unique genetic make-up. As a result, some variations that are very rare in other populations may be more common in Finland, making them easier to detect and study.

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Noncoding RNAs Not So Noncoding

Noncoding RNAs Not So Noncoding | Amazing Science |

In 2002, a group of plant researchers studying legumes at the Max Planck Institute for Plant Breeding Research in Cologne, Germany, discovered that a 679-nucleotide RNA believed to function in a noncoding capacity was in fact a protein-coding messenger RNA (mRNA).1 It had been classified as a long (or large) noncoding RNA (lncRNA) by virtue of being more than 200 nucleotides in length. The RNA, transcribed from a gene called early nodulin 40 (ENOD40), contained short open reading frames (ORFs)—putative protein-coding sequences bookended by start and stop codons—but the ORFs were so short that they had previously been overlooked.


When the Cologne collaborators examined the RNA more closely, however, they found that two of the ORFs did indeed encode tiny peptides: one of 12 and one of 24 amino acids. Sampling the legumes confirmed that these micropeptides were made in the plant, where they interacted with a sucrose-synthesizing enzyme.


Five years later, another ORF-containing mRNA that had been posing as a lncRNA was discovered inDrosophila.2,3 After performing a screen of fly embryos to find lncRNAs, Yuji Kageyama, then of the National Institute for Basic Biology in Okazaki, Japan, suppressed each transcript’s expression. “Only one showed a clear phenotype,” says Kageyama, now at Kobe University. Because embryos missing this particular RNA lacked certain cuticle features, giving them the appearance of smooth rice grains, the researchers named the RNA “polished rice” (pri).


Turning his attention to how the RNA functioned, Kageyama thought he should first rule out the possibility that it encoded proteins. But he couldn’t. “We actually found it was a protein-coding gene,” he says. “It was an accident—we are RNA people!” The pri gene turned out to encode four tiny peptides—three of 11 amino acids and one of 32—that Kageyama and colleagues showed are important for activating a key developmental transcription factor.4


Since then, a handful of other lncRNAs have switched to the mRNA ranks after being found to harbor micropeptide-encoding short ORFs (sORFs)—those less than 300 nucleotides in length. And given the vast number of documented lncRNAs—most of which have no known function—the chance of finding others that contain micropeptide codes seems high.


Genomes contain countless sORFs, but most do not produce functional proteins. To help identify the true protein-coding needles in the nonsense haystacks, scientists have devised methods and metrics to calculate sORFs’ coding potential based on their sequences and ribosome profiling characteristics.

Ribosome Release Score (RSS): After a ribosome reaches the stop codon of a true protein-coding mRNA, the ribosome’s association with the transcript ceases. The distribution of ribosome-bound fragments for those RNAs would thus show a dramatic reduction following the putative stop codon. (Cell, 154:240-51, 2013)

Fragment Length Organization Similarity Score (FLOSS):This metric distinguishes RNAs that have ribosome profiling fragment sizes clustered tightly in the 30–32 nucleotide range—the size protected by a eukaryotic ribosome—from those that have more varied fragment sizes, which might indicate protection by contaminating nonribosomal proteins. (Cell Rep, 8:1365-79, 2014)

ORF Regression Algorithm for Translation Evaluation of RPFs (ribosome-protected mRNA fragments) (ORF-RATER):This algorithm determines the likelihood that an ORF is translated based on its similarity to known protein-coding ORFs in terms of ribosome-occupancy pattern—that is, the distribution of ribosome profiling fragments across the ORF. For example, true protein-coding ORFs tend to exhibit peaks in the number of fragments at the start and stop codons where ribosomes are built and dismantled, and their fragments show a three-nucleotide periodicity in the expected reading frame—the ribosome appears to jump along three nucleotides (one codon) at a time. (Mol Cell, 60:816-27, 2015)

Phylogenetic Conservation Score of a sORF (PhyloCSF): This metric examines conservation of a sORF across species. (Bioinformatics, 27:i275-i282, 2011)

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The ultimate discovery power of the gene chip is coming to nanotechnology

The ultimate discovery power of the gene chip is coming to nanotechnology | Amazing Science |

The discovery power of the gene chip is coming to nanotechnology, as a Northwestern University research team develops a  tool to rapidly test millions — and perhaps even billions — of different nanoparticles at one time to zero in on the best nanoparticle for a specific use.


When materials are miniaturized, their properties — optical, structural, electrical, mechanical and chemical — change, offering new possibilities. But determining what nanoparticle size and composition are best for a given application, such as catalysts, biodiagnostic labels, pharmaceuticals and electronic devices, is a daunting task.


“As scientists, we’ve only just begun to investigate what materials can be made on the nanoscale,” said Northwestern’s Chad A. Mirkin, a world leader in nanotechnology research and its application, who led the study. “Screening a million potentially useful nanoparticles, for example, could take several lifetimes. Once optimized, our tool will enable researchers to pick the winner much faster than conventional methods. We have the ultimate discovery tool.”


Combinatorial libraries of nanoparticles - more than half never existed on Earth.


Using a Northwestern technique that deposits materials on a surface, Mirkin and his team figured out how to make combinatorial libraries of nanoparticles in a controlled way. (A combinatorial library is a collection of systematically varied structures encoded at specific sites on a surface.) Their study was published today (June 24) by the journal Science.

The nanoparticle libraries are much like a gene chip, Mirkin says, where thousands of different spots of DNA are used to identify the presence of a disease or toxin. Thousands of reactions can be done simultaneously, providing results in just a few hours. Similarly, Mirkin and his team’s libraries will enable scientists to rapidly make and screen millions to billions of nanoparticles of different compositions and sizes for desirable physical and chemical properties.


“The ability to make libraries of nanoparticles will open a new field of nanocombinatorics, where size — on a scale that matters — and composition become tunable parameters,” Mirkin said. “This is a powerful approach to discovery science.”

Mirkin is the George B. Rathmann Professor of Chemistry in the Weinberg College of Arts and Sciences and founding director of Northwestern’s International Institute for Nanotechnology.


Using just five metallic elements — gold, silver, cobalt, copper and nickel — Mirkin and his team developed an array of unique structures by varying every elemental combination. In previous work, the researchers had shown that particle diameter also can be varied deliberately on the 1- to 100-nanometer length scale.

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Genome sequencing helps determine end of tuberculosis outbreak

Genome sequencing helps determine end of tuberculosis outbreak | Amazing Science |

Using genome sequencing, researchers from the University of British Columbia, along with colleagues at the Imperial College in London, now have the ability to determine when a tuberculosis (TB) outbreak is over.


The research is the first of its kind to demonstrate that genomic analysis can be used to determine when a TB outbreak has ended—valuable knowledge which can assist public health investigators understand an outbreak’s dynamics and guide a real-time public health response. Genomic analysis involves reading the complete genetic instructions of the pathogens causing a disease, and using that data to infer who might have infected whom. By looking for mutations that are shared between the pathogens taken from different people, researchers can see whose pathogens are most closely related to each other, suggesting potential transmission.


“Declaring the end of a TB outbreak is a difficult thing to do,” said senior author Jennifer Gardy, assistant professor in UBC’s school of population and public health and a senior scientist at the British Columbia Centre for Disease Control. “Because the bacterium that causes TB can lie dormant in someone’s lung for months or even years before it causes disease, we had no way of knowing whether a TB case we have just diagnosed was a recent infection – suggesting the outbreak is still going on – or whether the person was infected years ago.”


Using mathematical and statistical techniques, the researchers evaluated a TB outbreak that began in May 2008 and were able to determine when each outbreak case was infected. This provided public health officials with a way to determine when disease transmission had stopped and the outbreak had ended. They were able to declare the outbreak over in January 2015, after the data indicated no disease transmission had occurred since mid-2012.


“By using a series of techniques from the world of mathematics and statistics, we can come up with an estimated time at which each infection occurred,” explained Gardy. “This information is incredibly useful to the public health officials managing an outbreak. Responding to an outbreak requires a lot of effort and resources, and we need to know when we can step down our response.”


“Genomics has been used to monitor infectious disease outbreaks before, but this is the first time it’s ever been possible to declare a complicated outbreak of TB over,” said Gardy. “It really opens up new doors in the world of TB control.”

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Cancer-patient big data can save lives if shared globally

Cancer-patient big data can save lives if shared globally | Amazing Science |

Sharing genetic information from millions of cancer patients around the world could revolutionize cancer prevention and care, according to a paper in Nature Medicine by the Cancer Task Team of the Global Alliance for Genomics and Health (GA4GH). Hospitals, laboratories and research facilities around the world hold huge amounts of this data from cancer patients, but it’s currently held in isolated “silos” that don’t talk to each other, according to GA4GH, a partnership between scientists, clinicians, patients, and the IT and Life Sciences industry, involving more than 400 organizations in over 40 countries. GA4GH intends to provide a common framework for the responsible, voluntary and secure sharing of patients’ clinical and genomic data.


“Imagine if we could create a searchable cancer database that allowed doctors to match patients from different parts of the world with suitable clinical trials,” said GA4GH co-chair professor Mark Lawler, a leading cancer expert fromQueen’s University Belfast. “This genetic matchmaking approach would allow us to develop personalized treatments for each individual’s cancer, precisely targeting rogue cells and improving outcomes for patients.


“This data sharing presents logistical, technical, and ethical challenges. Our paper highlights these challenges and proposes potential solutions to allow the sharing of data in a timely, responsible and effective manner. We hope this blueprint will be adopted by researchers around the world and enable a unified global approach to unlocking the value of data for enhanced patient care.”


GA4GH acknowledges that there are security issues, and has created a Security Working Group and a policy paper that documents the standards and implementation practices for protecting the privacy and security of shared genomic and clinical data.


Examples of current initiatives for clinico-genomic data-sharing include the U.S.-based Precision Medicine Initiative and the UK’s 100,000 Genomes Project, both of which have cancer as a major focus.


Herve Moal's curator insight, May 26, 2016 4:47 AM

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Scientists hold closed meeting to discuss building a human genome from scratch

Scientists hold closed meeting to discuss building a human genome from scratch | Amazing Science |

More than 130 scientists, lawyers, entrepreneurs, and government officials from five continents gathered at Harvard this week for an “exploratory” meeting to discuss the topic of creating genomes from scratch — including, but not limited to, those of humans, said George Church, Harvard geneticist and co-organizer of the meeting.  The meeting was closed to the press, which drew the ire of prominent academics.


Synthesizing genomes involves building them from the ground up — chemically combining molecules to create DNA. Similar work by Craig Venter in 2010 created what was hailed as the first synthetic cell, a bacterium with a comparatively small genome.


In recent months, Church has been vocal in saying that the much-hyped genome-editing technology called CRISPR, which is only a few years old and which he helped develop, would soon be obsolete. Instead of changing existing genomes through CRISPR, Church has said, scientists could build exactly the genomes they want from scratch, by stringing together off-the-shelf DNA letters.


The topic is a heavy one, touching on fundamental philosophical questions of meaning and being. If we can build a synthetic genome — and eventually, a creature — from the ground up, then what does it mean to be human?


“This idea is an enormous step for the human species, and it shouldn’t be discussed only behind closed doors,” said Laurie Zoloth, a professor of religious studies, bioethics, and medical humanities at Northwestern University.


In response, she co-authored an article with Drew Endy, a bioengineering professor at Stanford University, calling for broader conversations around the research.


Church said that the meeting was originally going to be “an open meeting with lots of journalists engaged.” It was supposed to be accompanied by a peer-reviewed article on the topic. But, he said, the journal (which Church declined to identify) wanted the paper to include more information about the ethical, social, and legal components of synthesizing genomes — things that were discussed at the meeting.

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Intron Addition into Genome Detected as an Ultra-rare Event

Intron Addition into Genome Detected as an Ultra-rare Event | Amazing Science |

After nearly a half trillion tries, a rare event was seen that might solve an evolutionary puzzle about noncoding sequences of DNA in genomes and address speciation and the cause of diseases like cancer.


For a long time, scientists have known that much of the DNA within any given organism’s genome does not code for functional molecules or protein. However, recent research has found that these genetic sequences, misnamed “junk” DNA in the past, often do have functional significance. These introns are no exception. Now known to play a role in gene expression, introns are the portion of gene sequences that are removed or spliced out of RNA before genes are translated into protein. When eukaryotes first diverged from bacteria, there was a massive invasion of introns into the genome. All living eukaryotes — from yeast to mammals — share this common ancestor, and whereas simple organisms such as yeast have eliminated most of their introns, organisms such as mammals have considerably expanded their intron inventory. Humans have more than 200,000 introns that take up about 40 percent of the genome.


In a current paper, Stevens and co-author Sujin Lee, a former graduate student in cellular and molecular biology at UT Austin, used a new reporter assay to directly detect the loss and gain of introns in budding yeast (Saccharomyces cerevisiae). The team tested nearly a half trillion yeast and found only two instances in which an intron was added to a new gene. The proposed mechanism for this addition is a reversal of a splicing reaction.


Normally, to make proteins, RNA is read from the instructions in DNA, and the introns are spliced out. But in these two instances, the cell allowed the spliced out introns to make it back into a different RNA and was recombined back into the genome, thus creating a permanent genetic change. These are called intron gains, and if these accumulate over time, they can contribute to the development of new species as well as human disease.


“We showed in this project that introns continue to be gained, although infrequently at any point in time,” says Stevens. “But can introns drive evolution? If these sequences give organisms a selective advantage and become fixed in a population, others have shown that it can be a major factor in the creation of new species.”


These evolutionary advances come at a cost, however, because diseases such as cancer correlate with the improper removal of introns from RNA. Stevens adds, “We are continuing this work to further understand how this process impacts our genetic history, our future, and the prospects of curing disease.”

Via Integrated DNA Technologies
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Genome Sequencing Reveals Differences Between Giraffes and Ocapi

Genome Sequencing Reveals Differences Between Giraffes and Ocapi | Amazing Science |

Scientists spot mutations that could explain how giraffes became the world’s tallest living mammals.


Call it a tall task: researchers have decoded the genomes of the giraffe and its closest relative, the okapi. The sequences, published on May 17 in Nature Communications, reveal clues to the age-old mystery of how the giraffe evolved its unusually long neck and legs.


Researchers in the United States and Tanzania analyzed the genetic material of two Masai giraffes (Giraffa camelopardalis tippelskirchi) from the Masai Mara National Reserve in Kenya, one at the Nashville Zoo in Tennessee and an okapi fetus (Okapia johnstoni) from the White Oak Conservation Center in Yulee, Florida.


“This is one more wonderful demonstration of the power of comparative genomics to connect the evolution of animal species on this planet to molecular events that we know must underpin the extraordinary diversity of life on this planet,” says David Haussler, director of the Genomics Institute at the University of California, Santa Cruz.


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Gamma-retroviruses preferentially integrate near cancer-associated genes

Gamma-retroviruses preferentially integrate near cancer-associated genes | Amazing Science |

Identifying the sites where gamma-retroviruses commonly insert into the genome may help to identify genes associated with specific cancer types, according to a study published April 20, 2016 in the open-access journal PLOS ONE by Kathryn Gilroy at the University of Glasgow, UK, and colleagues.


Gamma-retroviruses, such as feline leukaemia virus, tend to cause mutations when they insert into a host’s genome, and have been used as a tool to discover genes associated with cancer. However, this discovery process can be time consuming, requiring the collection of multiple tumors from animals and comparative genomic analyses. The authors of the present study sought to investigate the pattern of gamma-retrovirus insertion using deep sequencing to analyse common insertion sites for feline leukaemia virus in cell culture. The study was also expanded to analyze published genome insertion profiles of other gamma-retroviruses.


The authors found that the gamma-retroviruses preferentially inserted into cancer-driving genes, regardless of transcription levels, in a cell type-specific manner. This authors suggest that gamma-retrovirus integration profiling in vitro may be a tool to identify potential therapeutic target genes in different human cancer types.

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Scientists find link between genome and microbiome in Crohn’s disease patients

Scientists find link between genome and microbiome in Crohn’s disease patients | Amazing Science |
Genes linked to Crohn’s disease, an inflammatory bowel disease, might make people’s immune cells miss out on helpful messages sent by friendly gut bacteria.


Good gut bacteria might not help people with Crohn’s disease.

Protective microbial messages go unread in mice and in human immune cells with certain defective genes, researchers report online May 5 in Science. The findings are the first to tie together the roles of genes and beneficial microbes in the inflammatory bowel disease, says biologist Brett Finlay of the University of British Columbia in Vancouver, who was not involved in the new work.


“This is a major step forward in this area,” he says. Human genes and friendly microbes work together to control inflammation, he says. “And when you muck that up, things can go awry.”


In Crohn’s disease, the immune system riles up too easily, trigging chronic inflammation. Scientists don’t know why exactly people’s immune systems go haywire. But researchers have linked the disease to glitches in nearly 200 genes, including ATG16L1 and NOD2, which typically help kill bad bacteria in the gut.


Researchers have also reported that people with Crohn’s have a different collection of gut microbes compared with that of healthy people, says study coauthor and Caltech microbiologist Sarkis Mazmanian.But though “there’s a huge body of literature on the genome and on the microbiome,” he says, “no one knew what the interplay was between the two.”


So his team explored a potential link using a friendly gut microbe called Bacteroides fragilis. The bacteria send out calming messages that tell the immune system to tone down inflammation. Like letters inside envelopes, these messages travel in protective pouches called outer membrane vesicles, or OMVs.


Feeding OMVs to mice typically protects them from developing inflamed colons, or colitis — but not mice lacking the Crohn’s-linked genes ATG16L1 and NOD2. When researchers treated those mice with a colitis-causing chemical, they succumbed to the disease, even after eating OMVs.


Mice with defective versions of ATG16L1 and NOD2 “can’t reap the benefits of the beneficial microbiota,” Mazmanian says.Immune cells from human patients with the defective genes didn’t respond to OMVs either.


The findings suggest that the genes that kill bad bacteria also work with good bacteria to keep people’s immune systems from going out of control, says gastroenterologist Balfour Sartor of the University of North Carolina School of Medicine in Chapel Hill. The work “opens up a new mechanism for protection,” he says.

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The octopus genome and the evolution of cephalopod neural and morphological novelties

The octopus genome and the evolution of cephalopod neural and morphological novelties | Amazing Science |

Coleoid cephalopods (octopus, squid and cuttlefish) are active, resourceful predators with a rich behavioural repertoire. They have the largest nervous systems among the invertebrates and present other striking morphological innovations including camera-like eyes, prehensile arms, a highly derived early embryogenesis and a remarkably sophisticated adaptive colouration system. To investigate the molecular bases of cephalopod brain and body innovations, a group of scientists now sequenced the genome and multiple transcriptomes of the California two-spot octopus, Octopus bimaculoides. They found no evidence for hypothesized whole-genome duplications in the octopus lineage. The core developmental and neuronal gene repertoire of the octopus is broadly similar to that found across invertebrate bilaterians, except for massive expansions in two gene families previously thought to be uniquely enlarged in vertebrates: the protocadherins, which regulate neuronal development, and the C2H2 superfamily of zinc-finger transcription factors.


Extensive messenger RNA editing generates transcript and protein diversity in genes involved in neural excitability, as previously described, as well as in genes participating in a broad range of other cellular functions. The researchers identified hundreds of cephalopod-specific genes, many of which showed elevated expression levels in such specialized structures as the skin, the suckers and the nervous system. They also found evidence for large-scale genomic rearrangements that are closely associated with transposable element expansions.


In summary, the present analysis suggests that substantial expansion of a handful of gene families, along with extensive remodelling of genome linkage and repetitive content, played a critical role in the evolution of cephalopod morphological innovations, including their large and complex nervous systems.

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How Craig Venter is fighting ageing with genome sequencing

How Craig Venter is fighting ageing with genome sequencing | Amazing Science |

Nine years ago, Craig Venter sequenced the first complete individual human genome - his own. Now, he's finally starting to decode what it means for his future. 

Via Integrated DNA Technologies
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Small handheld device tracks disease mutations within minutes

QuantuMDx Group is one of the most exciting biotechs to emerge from the UK and is developing a low cost, simple-to-use, handheld laboratory for 15-minute diagnosis of disease at the patient's side, for commercialisation in 2015. The robust device, which reads and sequences DNA and converts it into binary code using a tiny computer chip, is ideally suited to help address the humanitarian health burden by offering molecular diagnostics at a fraction of the price of traditional testing.


Rapidly & accurately detecting and monitoring emerging drug resistance of infectious diseases such as malaria, TB and HIV will enable health professionals to immediately prescribe the most effective drug against that disease. Once the device has passed regulatory approval, it will be available in developed countries for infectious disease testing and rapid cancer profiling and, in time, be available over-the-counter at pharmacies.


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