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Category Archives: Genome

3Q: Behind the scenes of the National Academy of Sciences’ report on human genome editing – The MIT Tech

Posted: at 2:50 pm

When the National Academy of Sciences (NAS) released its Human Genome Editing Report last week, a wave of questions arose regarding the reports scientific and clinical implications. The report, which outlines criteria that should be met before allowing clinical trials involving germline editing to go forward, was issued in response to the promising research and clinical opportunities associated with powerful genome-editing tools such as CRISPR/Cas9.

Richard O. Hynes is a Daniel K. Ludwig Professor for Cancer Research at MIT, a member of MIT’s Koch Institute for Integrative Cancer Research, and a former director of the Koch Institute’s predecessor, the MIT Center for Cancer Research. Hynes, a co-chair of the NAS study committee that created the report, sat down to shed additional light on the reports recommendations and its impact on the future of genome editing.

Q: Why is a report like this needed now?

A: We are in the midst of an explosion of new research and clinical opportunities that can be enabled by genome-editing tools. Genome editing is now much easier, faster, cheaper, and more versatile than ever. Because this field is advancing so rapidly, the issues and concerns that genome editing raises needed to be seriously reviewed and addressed, alongside the development of the technology itself.

There are, of course, many technical questions such as what risks exist, how to reduce them, and how to regulate the different ongoing applications which need to be explored further, but there are plenty of societal questions as well. For example, should one allow enhancement or going beyond treatment and prevention of disease and disability? Should heritable germline editing be allowed, if and when it might become sufficiently reproducible, accurate, and safe? And if so, how would that affect societal attitudes toward disability, issues of equity and fairness, and concerns around creating a slippery slope that could lead to inappropriate applications?

The reports committee represented four continents and included scientists, clinicians, ethicists, lawyers, and public engagement experts, among others. Each member offered a unique perspective on how oversight guidelines should be crafted and regulated and how to further public discussion. We believe the resulting recommendations will have universal applicability across multiple countries and cultures, and we recommend a set of principles that could be incorporated into the regulation and oversight in any country pursuing human genome editing.

Q: What are the reports primary take-home points?

A: First, human genome editing in the contexts of basic laboratory research, and somatic gene therapy for the treatment and prevention of disease and disability are valuable and well-regulated. They should proceed under the existing oversight and regulatory norms.

Second, editing for purposes other than treatment or prevention of disease and disability should not be approved at this time. Public engagement and discussion on this topic should be actively promoted before advancing past these purposes, and specific funding should be allotted to support this.

Finally, while human heritable germline editing is not yet practicable and much further research is necessary before it could be considered for clinical trials, there are arguments for limited applications to prevent heritable disease should that become feasible. At the same time, there are technical, practical, societal, and ethical concerns that need to be addressed. The report lays out a set of stringent criteria that would need to be met for approval of any trial of heritable germline editing, and it recommends extensive public engagement in discussionsabout how to assess its implications before any such trials.

Q: Are there any misconceptions about the report that you would like to address?

A: Of course, there is always the potential for concern around these topics when they enter the public sphere, but this report is firmly grounded in existing ethical, scientific, and regulatory practices and in consultation with the individuals and communities who will be directly affected by this technology. I would say that the committee is not opening the door to human genome editing, but we are, so to speak, removing the padlock pending possible new applications. Furthermore, the report is recommending human applications only for purposes of treatment and prevention of disease or disability and not for any applications that go beyond that, such as enhancements.

We limited our recommendations to this because of concerns about making unnecessary, potentially risky edits aimed toenhance human capacities beyond what is necessary to treat a life-threatening or debilitating condition. Enhancement is a topic that needs more discussion and public engagement to assess societal attitudes. At this time, we say no to any germline enhancements. If technology moves forward to enable the possibility, our current recommendation would be that it should be used to enable healthy babies, notdesigner babies. We also have confidence in the current systems of regulation and decision-making based on risk/benefit analysis but believe it should incorporate more engagement with public opinion.

Overall, we have been pleased with the coverage of the report so far, and the public seems to be excited about the major acceleration of our understanding of human biology. There is real potential to combat many diseases, such as cancer and thousands of genetically inherited diseases, which affect a significant number of people in the global population. Somatic editing is already in clinical trials, and many more are yet to come that we will learn a great deal from particularly about efficacy, risks, and the impact of this modern form of gene therapy. Germline editing is not possible yet probably not for several years but it is time to think carefully about the implications while the technical aspectsare still being explored, rather than waiting until the decisions as to whether or not to proceed are imminent.

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Do you really want to know what’s lurking in your genome? – The Conversation UK

Posted: February 24, 2017 at 5:53 pm

Would you want to know if you were at a higher risk of getting dementia later in life? Would you want to know that you could die under general anaesthesia, or might die suddenly of heart failure? Would you want to know if you had a higher-than-normal chance of getting cancer? You could learn these things by looking at your genome. But would you want to be faced with the answers?

Your genome is the complete set of genetic information in the cells of your body. It is like a recipe book that provides the instructions for who you are, and the recipes are your genes. Each gene provides a set of instructions for the protein molecules that make up your body. Much like how your cake recipe might differ from your neighbours, these genetic recipes can differ slightly from person to person. However, if there is a significant error in the recipe for example, if baking powder were left out this can have a damaging effect on the final product. So, if there is a harmful variant in a gene, this can affect the protein produced, which can cause genetic disease.

When a doctor suspects that you have a genetic disease, they can now read your genome from cover to cover. After nearly 13 years of international collaboration, the first complete sequence of the human genome was unveiled in 2003. Since then, the cost of genome sequencing has dropped from 1 billion to less than 1,000 allowing genome sequencing to enter routine clinical care, and transforming the way we diagnose and treat disease.

NHS England is currently sequencing 100,000 genomes, and the US has plans to sequence 1m genomes. A 2015 study predicted that up to two billion people worldwide could have their genomes sequenced within the next decade comparable to the reach of the internet. With so many genomes getting sequenced, and increasing opportunities to get genetic information outside of the healthcare system, you could be next.

Genetic variants help shape who we are and can tell us a lot about ourselves. This ranges from rather harmless characteristics such as eye colour to potentially serious conditions. These include findings for which there is no treatment, such as genetic changes associated with an increased risk of Alzheimers, as well as medically actionable findings, such as genetic predispositions to breast cancer where screening and treatment is available. One to two per cent of people who undergo genome sequencing could have genetic changes that point to these serious but medically actionable conditions.

Sometimes, in genetic testing for one condition, we can find variants that point to other serious diseases. For example, genome sequencing of a patient with a heart condition could flag up an additional genetic variant associated with cancer. However, much of our understanding of these genetic variants comes from patients who have the associated disease, so we can safely assume that the genetic variant is at fault. But with more and more data, we are learning that more people have disease-causing variants than we expect to have the disease which means that simply carrying a variant doesnt necessarily mean disease will follow. So for this patient with a heart condition, interpreting variants that point to any other disease, such as cancer, is challenging.

There are other issues to consider. How would you feel if you were told you had a 90% increased risk of breast cancer or that you might die suddenly from a problem with your heart like some young athletes in the news? Even if our ability to understand these variants were stronger, would the benefit of knowing this information outweigh the potential anxiety it could cause?

Genetic variants arent the full picture the environment plays a role, too. There are also concerns around storage, security, privacy and discrimination. Further complicating all of this is the shared nature of genetic information. We share half of our genome with our parents, children and siblings, one quarter with our grandparents, aunts, uncles, nieces and nephews. Unlike a typical medical test, genetic results not only affect us, but our family members.

In the coming years, as these large genome sequencing projects are completed, our understanding of these variants will improve and policy will catch up with the technology. In the meantime, genome sequencing programmes including our own are offering these results to participants, generating the data needed to inform our understanding of these variants. These results, however, are optional: it is your choice whether or not you want them. So, before you provide a saliva sample to have your own genetic recipe book read, its important to know which results are worth knowing about.

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Biologists propose to sequence the DNA of all life on Earth – Science Magazine

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Can biologists sequence the genomes of all the plants and the animals in the world, including this greater bird of paradise in Indonesia?

TIM LAMAN/National Geographic Creative

By Elizabeth PennisiFeb. 24, 2017 , 1:15 PM

WASHINGTON, D.C.When it comes to genome sequencing, visionaries like to throw around big numbers: Theres the UK Biobank, for example, which promises to decipher the genomes of 500,000 individuals, or Icelands effort to study the genomes of its entire human population. Yesterday, at a meeting here organized by the Smithsonian Initiative onBiodiversity Genomics and the Shenzhen, Chinabased sequencing powerhouse BGI, a small group of researchers upped the ante even more, announcing their intent to, eventually, sequence all life on Earth.

Their plan, which does not yet have funding dedicated to it specifically but could cost at least several billions of dollars, has been dubbed the Earth BioGenome Project (EBP). Harris Lewin, an evolutionary genomicist at the University of California, Davis, who is part of the group that came up with this vision 2 years ago, says the EBP would take a first step toward its audacious goal by focusing on eukaryotesthe group of organisms that includes all plants, animals, and single-celled organisms such as amoebas.

That strategy, and the EBPs overall concept, found a receptive audience at BioGenomics2017, a gathering this week of conservationists, evolutionary biologists, systematists, and other biologists interested in applying genomics to their work. This is a grand idea, says Oliver Ryder, a conservation biologist at the San Diego Zoo Institute for Conservation Research in California. If we really want to understand how life evolved, genome biology is going to be part of that.

Ryder and others drew parallels between the EBP and the Human Genome Project, which began as an ambitious, controversial, and, at the time, technically impossible proposal more than 30 years ago.That earlier effort eventually led not only to the sequencing of the first human genome, but also to entirely new DNA technologies that are at the center of many medical frontiers and the basis for a $20 billion industry. People have learned from the human genome experience that [sequencing] is a tremendous advance in biology, Lewin says.

Many details about the EBP are still being worked out. But as currently proposed, the first step would be to sequence in great detail the DNA of a member of each eukaryotic family (about 9000 in all) to create reference genomes on par or better than the reference human genome. Next would come sequencing to a lesser degree a species from each of the 150,000 to 200,000 genera. Finally, EBP participants would get rough genomes of the 1.5 million remaining known eukaryotic species. These lower resolution genomes could be improved as needed by comparing them with the family references or by doing more sequencing, says EBP co-organizer Gene Robinson, a behavioral genomics researcher and director of the Carl R. Woese Institute for Genomic Biology at the University of Illinois in Urbana.

In this representation of the tree of life, there are very few completed genomes (red lines in inner rim) among named eukaryotes (green), but many more among bacteria (blue) and archaea (purple). Among the millions of eukaryotic species, there are even relatively few lower resolution genome sequences (blue, light and dark gray).

Keith A. Crandall, David B. Stern, and Jimmy Bernot of The George Washington Universitys Computational Biology Institute

The entire eukaryotic effort would likely cost about the same as it did to sequence that first human genome, estimate Lewin, Robinson, and EBP co-organizer John Kress, an evolutionary biologist at the Smithsonian National Museum of Natural History here. It took about $2.7 billion to read and order the 3 billion bases composing the human genome, about $4.8 billion in todays dollars. With a comparable amount of support, the EBPs eukaryotic work might be done in a decade, its organizers suggest.

Such optimism arises from ever-decreasing DNA sequencing costsone meeting presenter fromComplete Genomics, based in Mountain View, California, says his company plans to be able to roughly sequence whole eukaryotic genomes for about $100 within a yearand improvements in sequencing technology that make possible higher quality genomes, at reasonable prices. It became apparent to me that at a certain point, it would be possible to sequence all life on Earth, Lewin says.

Although some may find the multibillion-dollar price tag hard to justify for researchers not studying humans, the fundamentals of matter, or the mysteries of the universe, the EBP has a head start, thanks to the work of several research communities pursuing their own ambitious sequencing projects. These include the Genome 10K Project, which seeks to sequence 10,000 vertebrate genomes, one from each genus; i5K, an effort to decipher 5000 arthropods; and B10K, which expects to generate genomes for all 10,500 bird species. The EBP would help coordinate, compile, and perhaps fund these efforts. The [EBP] concept is a community of communities, Lewin says.

There are also sequencing commitments from giants in the genomics field, such as Chinas BGI, and the Wellcome Trust Sanger Institute in the United Kingdom. But at a planning meeting this week, it became clear that significant challenges await the EBP, even beyond funding. Although researchers from Brazil, China, and the United Kingdom said their nations are eager to participate in some way, the 20 people in attendance emphasized the need for the effort to be more international, with developing countries, particularly those with high biodiversity, helping shape the projects final form. They proposed that the EBP could help develop sequencing and other technological experts and capabilities in those regions. The Global Genome Biodiversity Network, which is compiling lists and images of specimens at museums and other biorepositories around the world, could supply much of the DNA needed, but even broader participation is important, says Thomas Gilbert, an evolutionary biologist at the Natural History Museum of Denmark in Copenhagen.

The planning group also stressed the need to develop standards to ensure high-quality genome sequences and to preserve associated information for each organism sequenced, such as where it was collected and what it looked like. Getting DNA samples from the wild may ultimately be the biggest challengeand the biggest cost, several people noted. Not all museum specimens yield DNA preserved well enough for high-quality genomes. Even recently collected and frozen plant and animal specimens are not always handled correctly for preserving their DNA, says Guojie Zhang, an evolutionary biologist at BGI and the University of Copenhagen. And the lack of standards could undermine the projects ultimate utility, notes Erich Jarvis, a neurobiologist at The Rockefeller University in New York City: We could spend money on an effort for all species on the planet, but we could generate a lot of crap.

But Lewin is optimistic that wont happen. After he outlined the EBP in the closing talk at BioGenomics2017, he was surrounded by researchers eager to know what they could do to help. Its good to try to bring together the tribes, says Jose Lopez, a biologist from Nova Southeastern University in Fort Lauderdale, Florida, whose tribe has mounted GIGA, a project to sequence 7000 marine invertebrates. Its a big endeavor. We need lots of expertise and lots of people who can contribute.

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Biologists propose to sequence the DNA of all life on Earth – Science Magazine

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The Mysterious 98%: Scientists Look to Shine Light on Our Dark Genome – ScienceBlog.com (blog)

Posted: February 23, 2017 at 12:48 pm

After the 2003 completion of the Human Genome Project which sequenced all 3 billionletters,or base pairs, in the human genome many thought that our DNA would become an open book. But a perplexing problem quickly emerged: although scientists could transcribe the book, they could only interpret a small percentage of it.

The mysterious majority as much as 98 percent of our DNA do not code for proteins. Much of this dark matter genome is thought to be nonfunctional evolutionary leftovers that are just along for the ride. However, hidden among this noncoding DNA are many crucial regulatory elements that control the activity of thousands of genes. What is more, these elements play a major role in diseases such as cancer, heart disease, and autism, and they could hold the key to possible cures.

As part of a major ongoing effort to fully map and annotate the functional sequences of the human genome,including this silent majority, the National Institutes of Health (NIH)on Feb. 2, 2017, announced new grant funding for a nationwide project to set up five characterization centers, including two at UC San Francisco, to study how theseregulatory elements influence gene expression and, consequently, cell behavior.

The projects aim is for scientists to use the latest technology, such as genome editing, to gain insights into human biology that could one day lead to treatments for complex genetic diseases.

After the shortfalls of the Human Genome Project became clear, the Encyclopedia of DNA Elements (ENCODE) Project was launched in September 2003 by the National Human Genome Research Institute (NHGRI). The goal of ENCODE is to find all the functional regions of the human genome, whether they form genes or not.

The Human Genome Project mapped the letters of the human genome, but it didnt tell us anything about the grammar: where the punctuation is, where the starts and ends are.

Elise Feingold, PhD

NIH Program Director

The Human Genome Project mapped the letters of the human genome, but it didnt tell us anything about the grammar: where the punctuation is, where the starts and ends are, said NIH Program Director Elise Feingold, PhD. Thats what ENCODE is trying to do.

The initiative revealed that millions of these noncoding letter sequences perform essential regulatory actions, like turning genes on or off in different types of cells. However, while scientists have established that these regulatory sequences have important functions, they do not know what function each sequence performs, nor do they know which gene each one affects. That is because the sequences are often located far from their target genes in some cases millions of letters away. Whats more, many of the sequences have different effects in different types of cells.

The new grants from NHGRI will allow the five new centers to work to define the functions and gene targets of these regulatory sequences. At UCSF, two of the centers will be based in the labs of Nadav Ahituv, PhD, and Yin Shen, PhD. The other three characterization centers will be housed at Stanford University, Cornell University, and the Lawrence Berkeley National Laboratory. Additional centers will continue to focus on mapping, computational analysis, data analysis and data coordination.

New technology has made identifying the function and targets of regulatory sequences much easier. Scientists can now manipulate cells to obtain more information about their DNA, and, thanks to high-throughput screening, they can do so in large batches, testing thousands of sequences in one experiment instead of one by one.

It used to be extremely difficult to test for function in the noncoding part of the genome, said Ahituv, a professor in the Department of Bioengineering and Therapeutic Sciences. With a gene, its easier to assess the effect because there is a change in the corresponding protein. But with regulatory sequences, you dont know what a change in DNA can lead to, so its hard to predict the functional output.

Ahituv and Shen are both using innovative techniques to study enhancers, which play a fundamental role in gene expression. Every cell in the human body contains the same DNA. What determines whether a cell is a skin cell or a brain cell or a heart cell is which genes are turned on and off. Enhancers are the secret switches that turn on cell-type specific genes.

During a previous phase of ENCODE, Ahituv and collaborator Jay Shendure, PhD, at the University of Washington, developed a technique called lentivirus-based massive parallel reporter assay to identify enhancers. With the new grant, they will use this technology to test for enhancers among 100,000 regulatory sequences previously identified by ENCODE.

Their approach pairs each regulatory sequence with a unique DNA barcode of 15 randomly generated letters. A reporter gene is stuck in between the sequence and the barcode, and the whole package is inserted into a cell. If the regulatory sequence is an enhancer, the reporter gene will turn on and activate the barcode. The DNA barcode will then code for RNA in the cell.

Once the researchers see that the reporter gene is turned on, they can easily sequence the RNA in the cell to see which barcode is activated. They then match the barcode back to its corresponding regulatory sequence, which the scientists now know is an enhancer.

With previous enhancer assays, you had to test each sequence one by one, Ahituv explained. With our approach, we can clone thousands of sequences along with thousands of barcodes and test them all at once.

Shen, an assistant professor in the Department of Neurology and the Institute for Human Genetics, is taking a different approach to characterize the function of regulatory sequences. In collaboration with her former mentor at the Ludwig Institute for Cancer Research and UC San Diego, Bing Ren, PhD, she developed a high-throughput CRISPR-Cas9 screening method to test the function of noncoding sequences. Now, Shen and Ren are using this approach to identify not only which sequences have regulatory functions, but also which genes they affect.

Shen will use CRISPR to edit tens of thousands of regulatory sequences in a large pool of cells and track the effects of the edits on a set of 60 pairs of genes that commonly co-express.

For this work, each cell will be programmed to reflect two fluorescent colors one for each gene when a pair of genes is turned on. If the light in a cell goes out, the scientists will know that its target gene has been affected by one of the CRISPR-based sequence edits. The final step is to sequence each cells DNA to determine which regulatory sequence edit caused the change in gene expression.

By monitoring the colors of co-expressed genes, Shen will reveal the complex relationship between numerous functional sequences and multiple genes, which was beyond the scope of traditional sequencing techniques.

Until the recent development of CRISPR, it was not possible to genetically manipulate non-coding sequences in a large scale, said Shen. Now, CRISPR can be scaled up so that we can screen thousands of regulatory sequences in one experiment. This approach will tell us not only which sequences are functional in a cell, but also which gene they regulate.

By cataloging the functions of thousands of regulatory sequences, Shen and Ahituv hope to develop rules about how to predict and interpret other sequences functions. This would not only help illuminate the rest of the dark matter genome, it could also reveal new treatment targets for complex genetic diseases.

A lot of human diseases have been found to be associated with regulatory sequences, Ahituv said. For example, in genome-wide association studies for common diseases, such as diabetes, cancer and autism, 90 percent of the disease-associated DNA variants are in the noncoding DNA. So its not a gene thats changed, but what regulates it.

As the price for sequencing a persons genome has dropped significantly, there is talk about using precision medicine to cure many serious diseases. However, the hurdle of how to interpret mutations in noncoding DNA remains.

If we can characterize the function and identify the gene targets of these regulatory sequences, we can start to reveal how their mutations contribute to diseases, Shen said. Eventually, we may even be able to treat complex diseases by correcting regulatory mutations.

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The power and the fear of knowing your cancer genome – STAT

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W

hen it comes to cancer, all knowledge is power even when that knowledge is scary. Knowing as much as you can about cancer lets you and your health care team act decisively in devising your treatment strategy. Even more important, it lets you act specifically in selecting treatments or clinical trials that might be best in treating your disease.

Advances in genomics and molecular biology have revealed that cancer is surprisingly, shockingly diverse so much so that we no longer view most cancers as one disease, even those that begin in the same organ or tissue. For example, there are at least 12 subtypes of multiple myeloma, the rare cancer that I have. Each one can be defined by a complex interplay of genetic mutations and other molecular abnormalities, some of which are shared with cancers that originate elsewhere in the body.

For me, learning everything about my disease has been essential to discovering how to attack and treat my cancer and, I believe, why I went into a surprising but welcome long-lasting remission.

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I first had my bone marrow analyzed in 1996, shortly after I was diagnosed with multiple myeloma. The procedure used, fluorescence in situ hybridization (FISH), was the gold standard test at the time to detect certain mutations that might shed light on my prognosis and treatment. It showed I had a type of genetic mutation called t(4;14). It meant that parts of two different chromosomes had switched places.

I will never forget how terrified, how heartbroken I felt when I learned that t(4;14) meant that my already fatal disease was of a particularly aggressive subtype. My remissions would be short, my relapses frequent.

Kathy Giusti: The businesswoman who took on her own cancer

But as I sat with that devastating news, a new drug called Velcade was in development that would change my fate. In spite of, or perhaps because of, our t(4;14) status, individuals like me tend to respond well to Velcade so well that it can help overcome the dismal prognosis conferred by this mutation. Fortunately, with the appropriate treatment, here I am, living life to the fullest 20 years after being diagnosed with a cancer that my doctors thought would kill me in three to four years.

My personal experience reveals just how complex cancer truly is and the powerful role patients can play in contributing to our understanding of cancer. Today, in addition to FISH and other tests like gene expression profiling, a growing number of patients are having their tumors sequenced. This involves comparing your healthy DNA with your cancers DNA. This can pinpoint genetic mutations that give rise to the disease and helps guide treatment of an ever-growing number of cancers.

Some cancer centers already routinely sequence all patients with cancer. Others sequence patients with cancers that arise from well-understood mutations, such as melanoma or colon cancer, for which targeted drug therapies exist.

And it is increasingly common to do gene sequencing for patients with rare cancers, or those whose treatment options have run out, in the hopes that this genetic information can identify a known mutation for which an existing treatment is available often one used for an entirely different form of cancer.

As we sequence and analyze many patient genomes, and learn from that knowledge, we will identify other genetic mutations and abnormalities that give rise to cancer and learn how they affect the treatment path. These predictive insights will benefit not just the individual, but all people with cancer.

Theres no denying that patients may gain knowledge about their cancer that they wish they hadnt. They might find out that their cancer is more aggressive than blood tests or imaging studies had led them and their doctors to believe. They might learn they are at greater risk of certain side effects or complications, or that some drugs just wont work for them.

Still, as someone who has heard both good and bad news about my cancer genome, I would choose knowledge no matter what.

Thats why I urge all patients to have their cancer sequenced. If the technology isnt available, have a sample of tumor tissue banked so it can be sequenced at a later date and, in the meantime, have the tumor analyzed by FISH or gene expression profiling, both of which are very accessible.

But dont stop there. I strongly encourage patients to know the results of this testing. What is my disease sub-type? Am I at high risk? Knowing the answers to these questions may point to potentially lifesaving treatment strategies.

Cancer patients can help build knowledge about this set of diseases by raising our hands for research. My organization, the Multiple Myeloma Research Foundation, conducted the CoMMpass Study. It sequenced the genomes of 1,000 patients with multiple myeloma and then linked that information to patients clinical history what treatments worked for them, what didnt to uncover additional mutations associated with the disease.

CoMMpass unearthed a mutation in whats called the BRAF gene that had never before been linked to myeloma. Most recently it discovered that there are further subtypes within the t(4;14) subtype. One of these appears to confer no worse prognosis than is associated with other subtypes, while another appears to be associated with an extremely fatal form of the disease.

As we continue to build upon our understanding of multiple myeloma, we take our ideas straight to the clinic, where patients can benefit from treatments that are tailored to the unique aspects of their cancer. Based on findings from the CoMMPass study, weve designed and launched clinical trials of drugs that target mutations in BRAF and in p53, a gene often associated with cancer. We also launched a trial specifically for patients with t(4;14) to pinpoint the characteristics genomic and otherwise that contribute to how well a person responds to therapy.

Choose the cancer center thats right for your cancer

This kind of innovation cannot be done alone nor should it. It requires the extensive analysis of a massive amount of patient data. This means that patients who are able to have their genomes sequenced should step up for research and share their data and other health information.

Myeloma patients can do that in our CoMMunity Gateway. There they can share as much or as little about their disease journey as they want, but can also connect with other patients like them and join clinical trials for their subtype as they become available.Other cancer-focused organizations offer similar resources.

To make sense of the data that are swelling into a flood, the global scientific community in clinical medicine, academia, and the biotech and pharmaceutical industries must work as a team. We must also reach across disciplines to create a diverse and powerful brain trust and build partnerships with diagnostic companies, who develop tests to screen for genetic changes, and insurance companies, who see the value in these diagnostics and are willing to pay for them.

While this work might not defeat cancer immediately, it paves the path for future innovation and potentially game-changing therapies.

Kathy Giusti is the founder of the Multiple Myeloma Research Foundation.She is also a senior fellow at Harvard Business School, where she serves as faculty co-chair of the schools Kraft Precision Medicine Accelerator.

Follow Kathy on Twitter @KathyGiusti

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The power and the fear of knowing your cancer genome – STAT

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Diving deep into the dolphin genome could benefit human health – Phys.Org

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February 23, 2017 Dolphins and humans are very similar creatures. A new database of bottlenose dolphin DNA and associated proteins could possibly aid in dolphin care and research on human medical problems such as stroke and kidney failure. Credit: NOAA

In movies and TV shows, dolphins are often portrayed as heroes who save humans through remarkable feats of strength and tenacity. Now dolphins could save the day for humans in real life, too with the help of emerging technology that can measure thousands of proteins and an improved database full of genetic data.

“Dolphins and humans are very, very similar creatures,” said NIST’s Ben Neely, a member of the Marine Biochemical Sciences Group and the lead on a new project at the Hollings Marine Laboratory, a research facility in Charleston, South Carolina that includes the National Institute of Standards and Technology (NIST) as one of its partner institutions. “As mammals, we share a number of proteins and our bodies function in many similar ways, even though we are terrestrial and dolphins live in the water all their lives.”

Neely and his colleagues have just finished creating a detailed, searchable index of all the proteins found in the bottlenose dolphin genome. A genome is the complete set of genetic material present in an organism. Neely’s project is built on years of marine mammal research and aims to provide a new level of bioanalytical measurements. The results of this work will aid wildlife biologists, veterinary professionals and biomedical researchers.

Protein Maps Could Help Dolphins and Humans

Although a detailed map of the bottlenose dolphin (Tursiops truncatus) genome was first compiled in 2008, recent technological breakthroughs enabled the creation of a new, more exhaustive map of all of the proteins produced by the dolphins’ DNA.

Neely led the process to generate the new genome with the help of colleagues at the Hollings Marine Laboratory. For this project, the initial genomic sequencing and assembly were completed by Dovetail Genomics , a private U.S.-based company. Next, the genome was annotated by the National Center for Biotechnology Information at the National Library of Medicine (NCBI) using previously deposited data generated in large part by the National Oceanic and Atmospheric Administration’s National Centers for Coastal Ocean Science Marine Genomics Core.

“Once you can identify all of the proteins and know their amounts as expressed by the genome,” Neely explained, “you can figure out what’s going on in the bottlenose dolphin’s biological systems in this really detailed manner.”

Neely’s study is part of an emerging field called proteomics. In the case of dolphins, proteomic work has a wide variety of potential applications.

The zoo and aquarium industry, which generates revenues of approximately $16 billion a year, could use it to improve the care of bottlenose dolphins.

In addition, improved dolphin proteomics could improve assessments of wild dolphin populations, and provide an immense amount of data on environmental contaminants and the safety and health of the world’s oceanic food web.

Comparing the proteins of humans and these other mammals is already providing researchers with a wealth of new information about how the human body works. Those findings could eventually be used to develop new, more precise treatment methods for common medical problems.

As marine mammals descend, they shut off the blood flow to many of their organs, which has long puzzled and intrigued biologists. In contrast, if blood stops flowing to the organs of a human’s body for even a few seconds, the result can be a stroke, kidney failure, or even death.

Studies have recently revealed that lesser-known proteins in the blood of marine mammals may be playing a big role in the dives by protecting bottlenose dolphins’ kidneys and hearts from damage when blood flow and oxygen flow start and stop repeatedly during those underwater forays.

One of these proteins is known as vanin-1. Humans produce vanin-1, but in much smaller amounts. Researchers would like to gather more information on whether or not elevating levels of vanin-1 may offer protection to kidneys.

“There’s this gap in the knowledge about genes and the proteins they make. We are missing a huge piece of the puzzle in how these animals do what they do,” said Mike Janech from the Medical University of South Carolina. His group has been researching vanin-1 and has identified numerous other potential biomedical applications for the dolphin genome just created by NIST.

“Genes carry the information of life,” Janech said. “But proteins execute the functions.”

From Macro to Micro

Vanin-1 is just one example of how genomic information about this mammalian cousin might prove useful. There may be hundreds of other similar applications, including some related to the treatment of high blood pressure and diabetes.

This represents another avenue for biomimicry, which seeks solutions to human problems by examining and imitating nature’s patterns and strategies. In the past, biomimicry was solely focused on the structural aspects of animal body parts such as arms and legs or functional patterns of things like noses and sniffing. But as the study of DNA has evolved, so too has our ability to examine the things happening at the most minute levels within another mammal’s body.

“We are now entering what could be called the post-model-organism era,” Neely said. Instead of looking only for a structure to model, imitate or learn from, scientists are looking at the complete molecular landscape of genes and proteins of these creatures for model processes, too. “With abundant genomic resources it is now possible to study non-model organisms with similar molecular machinery in order to tackle difficult biomedical problems.”

Data, New Technology and High-Quality Tissue Samples

To gather the needed protein information, Neely and his team used a specimen provided by the National Marine Mammal Tissue Bank (NMMTB), the longest running project of NIST’s Marine Environmental Specimen Bank. Half of the approximately 4,000 marine mammal specimens in the NMMTB are collected as a part of the Marine Mammal Health and Stranding Response Program . The specimen provided for Neely’s study was known to originate very close to the Hollings Marine Lab.

The new, state-of-the-art genome immediately began providing new biochemical insights. Studies at NIST are ongoing to validate the updated protein maps using an ultra-high-resolution tribrid mass spectrometer, which is the most powerful tool available to identify and quantify proteins.

Other Mammal Proteins Seem Promising, Too

Neely said the results demonstrate the utility of re-mapping genomes with the improved bioanalytical capabilities provided by new genomic sequencing technology coupled to high-resolution mass spectrometers. The data from this project will also be available in the public domain so that the results will be easy for others to access and use for diverse applications and research.

This is the first of many such projects to be undertaken by the Charleston group whereby new analytical techniques could be applied to marine animals. Studying other diving marine mammals can improve our understanding of the molecular mechanisms involved in diving. Also, sea lion proteins may have much to tell us about metastatic cancer, which especially intrigues Neely and his colleagues.

As a research chemist, Neely says he has not really spent much time before now observing marine mammals as a part of his work hours. He does encounter dolphins when he goes out surfing along the Carolina coastline, though.

“It’s amazing to think that we are at a point where cutting-edge research in marine mammals can directly advance human biomedical discoveries,” he said.

Explore further: Researchers probing the beneficial secrets in dolphins’ proteins

Why reinvent the wheel when nature has the answer?

Answers to evolutionary and ecological mysteries about marine mammal species may be closer at hand, thanks to advances in genetic sequencing techniques for so-called nonmodel organisms.

(Phys.org)A team of researchers with members from institutions in Australia, the U.S. and the U.K. has found evidence that suggests increased dolphin familiarity with humans has led to an increase in injury and death to …

(PhysOrg.com) — Marine mammal experts have uncovered a new species of dolphin in Australian waters, challenging existing knowledge about bottlenose dolphin classifications and highlighting the country’s marine biodiversity.

Bottlenose dolphins in the Florida Coastal Everglades have higher concentrations of mercury than any other populations in the world.

After years of research on dolphin behavior and under pressure from animal rights groups, the National Aquarium in Baltimore has decided to move the marine mammals to a sanctuary, officials said Wednesday.

The last Neanderthal died 40,000 years ago, but much of their genome lives on, in bits and pieces, through modern humans. The impact of Neanderthals’ genetic contribution has been uncertain: Do these snippets affect our genome’s …

In the middle of Alberta’s boreal forest, a bird eats a wild chokecherry. During his scavenging, the bird is caught and eaten by a fox. The cherry seed, now inside the belly of the bird within the belly of fox, is transported …

Sexual reproduction and viral infections actually have a lot in common. According to new research, both processes rely on a single protein that enables the seamless fusion of two cells, such as a sperm cell and egg cell, …

We all do it; we all need ithumans and animals alike. Sleep is an essential behavior shared by nearly all animals and disruption of this process is associated with an array of physiological and behavioral deficits. Although …

Professor Robert Sinclair at the Okinawa Institute of Science and Technology Graduate University (OIST) and Professor Dennis Bamford and Dr. Janne Ravantti from the University of Helsinki have found new evidence to support …

A common roundworm widely studied for its developmental biology and neuroscience, also might be one of the most surprising examples of the eat-local movement. Princeton University researchers have found that the organisms …

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Diving deep into the dolphin genome could benefit human health – Phys.Org

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Honey bee parasite genome sequenced to aid in fight against bee colony destruction – Phys.Org

Posted: at 12:48 pm

February 22, 2017 Three adult female Tropilaelaps mercedesae infesting the 5th instar honey bee larva. Credit: Dong et. al, Draft genome of the honey bee ectoparasitic mite, Tropilaelaps mercedesae, is shaped by the parasitic life history. GigaScience 2017

Published today in the open-access journal GigaScience is an article that presents the genome of a parasitic mite, Tropilaelaps mercedesae, that infects bee colonies, which are facing wide-spread devastation across the entire world. The research was carried out by an international team of researchers at Jiaotong-Liverpool University and Liverpool University and focused on mites as they are one of the major threats to honey bee colonies. The work revealed that there were specific features in the T. mercedesae mite genome that had been shaped by their interaction with honey bees, and that current mechanisms to control mites are unlikely to be useful for T. mercedesae. The genome sequence and findings provide excellent resources for identifying gene-based mite control strategies and understanding mite biology.

Although there are many potential causes for the decline in honey bee colonies, pathogens and parasites of the honey bee, particularly mites, are considered major threats to honey bee health and honey bee colonies. The bee mite Tropilaelaps mercedesae is honey bee parasite prevalent in most Asian countries, and has a similar impact on bee colonies that the globally present bee mite Varroa destructor has. More, T. mercedesae and V. destructor typically co-exist in Asian bee colonies and with the global trade of honey bees T. mercedesae is likely become established world-wide, as occurred with V. destructor.

Given the ongoing international devastation of bee colonies, the researchers sequenced the genome of T. mercedesae, to assess the interaction between the parasite and host as well as provide a resource for the ongoing battle to save honey bee populations.

The authors identified the genetic components in the genome and compared these to the genome of free-living mites. As opposed to the free-living mites, T. mercedesae has a very specialized life history and habitat that depends strictly on the honey bee inside a stable colony. Thus, comparison of the genome and transcriptome sequences with those of internal and free-living mites revealed the specific features of the T. mercedesae genome and showed that they were shaped by interaction with the honey bee and colony environment.

Of particular interest, the authors found that the mite does not rely on sensing stimulatory chemicals to affect their behavior. The researchers noted that this discovery meant that, “control methods targeted to gustatory, olfactory, and ionotropic receptors are not effective.” Instead, control measures will have to use other targets when trying to disrupt chemical communication. The authors further highlighted that, “there will be a need to identify targets for biological control.”

The researchers indicated that there were additional difficulties for controlling the mites, saying “We found that T, mercedesae is enriched with detoxifying enzymes and pumps for the toxic xenobiotics and thus the mite quickly acquires miticide resistance. For developing chemical control methods, we need to search for compounds which may not be recognized by the above proteins.”

Relevant to this, the researchers investigated the bacteria that infect the bee mite, as little is known about these bacteria. The scientists discovered that the symbiote R. grylli-like bacteria is commonly present in T. mercedesae, and they suggested that “Manipulating symbiotic Rickettsiella grylli-like bacteria, which is associated with T, mercedesae, may also help us to develop novel control strategies.”

They further found that this bacteria was involved in horizontal gene transfer of Wolbachia genes into the mite genome. Wolbachia is a bacteria that commonly infects arthropods, but is not present in T. mercedesae. While the authors were not overly surprised at discovering the occurrence of horizontal gene transfer since it has been detected in about 33% of sequenced arthropod genomes, they did note that this “is the first example discovered in mites and ticks as far as we know”, and that, since no Wolbachia were currently infecting the mite, this indicated that Wolbachia was once a symbiont for T. mercedesae or its ancestor but it would have been replaced with R. grylli-like bacteria during evolution.”

The extent of honey bee colony destruction remains a complex problem, but one that has an extensive impact crop productivity since honey bees are needed for pollination of a variety of plants. Indeed, in several places in China, farm workers have begun to carry out manual pollination to maintain high crop yield in orchards. Thus, research and resources to help combat this global threat are needed now. The findings, genome, transcriptome, and proteome resources from T. mercedesae study add another weapon in the fight to save bee colonies.

Explore further: New insights on how bees battle deadly varroa mite by grooming

More information: GigaScience, DOI: 10.5524/100266

Journal reference: GigaScience

Provided by: GigaScience

In a new study published in the Journal of Apicultural Research, scientists have compared the ability of two strains of honey bees to defend themselves against the parasitic mite varroa by grooming the mites from their bodies.

Researchers in Hawaii and the UK report that the parasitic ‘Varroa’ mite has caused the Deformed Wing Virus (DWV) to proliferate in honey bee colonies.

An infestation of speck-sized Varroa destructor mites can wipe out an entire colony of honey bees in 2-3 years if left untreated. Pesticides help beekeepers rid their hives of these parasitic arthropods, which feed on the …

Honey bees are now fighting back aggressively against Varroa mites, thanks to Agricultural Research Service (ARS) efforts to develop bees with a genetic trait that allows them to more easily find the mites and toss them out …

Parasitic mites Varroa destructor together with the pesticide imidacloprid hamper bees in their search for pollen. The pesticide and the bee parasite reduce the honeybees’ flight capacity, causing bee colonies to weaken and …

A sister species of the Varroa destructor mite is developing the ability to parasitize European honeybees, threatening pollinators already hard pressed by pesticides, nutritional deficiencies and disease, a Purdue University …

The last Neanderthal died 40,000 years ago, but much of their genome lives on, in bits and pieces, through modern humans. The impact of Neanderthals’ genetic contribution has been uncertain: Do these snippets affect our genome’s …

In the middle of Alberta’s boreal forest, a bird eats a wild chokecherry. During his scavenging, the bird is caught and eaten by a fox. The cherry seed, now inside the belly of the bird within the belly of fox, is transported …

Sexual reproduction and viral infections actually have a lot in common. According to new research, both processes rely on a single protein that enables the seamless fusion of two cells, such as a sperm cell and egg cell, …

We all do it; we all need ithumans and animals alike. Sleep is an essential behavior shared by nearly all animals and disruption of this process is associated with an array of physiological and behavioral deficits. Although …

Professor Robert Sinclair at the Okinawa Institute of Science and Technology Graduate University (OIST) and Professor Dennis Bamford and Dr. Janne Ravantti from the University of Helsinki have found new evidence to support …

A common roundworm widely studied for its developmental biology and neuroscience, also might be one of the most surprising examples of the eat-local movement. Princeton University researchers have found that the organisms …

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Honey bee parasite genome sequenced to aid in fight against bee colony destruction – Phys.Org

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Genomics to hit mainstream with AI and $100 genome – Digital Health

Posted: at 12:48 pm

The dramatic drop in the cost of genome sequencing, combined with rapidly evolving artificial intelligence, is moving precision medicine into mainstream healthcare.

Sanjay Chikarmane, senior vice president at Illumina, told an briefing at HIMSS17 in Orlando on Monday that the US$100 genome is now in sight.

Illumina is an US company focused on genetics sequencing and analysing big data for biological insights.

The company is also the major partner for the UK Governments 100k Genome project, providing most of the infrastructure through a 78 million partnership with the Genomics England.

During the briefing, Illumina announced a new partnership with Philips. Illumina will use Philips new genomics AI platform to analyse genomics data, identify key mutations and provide the data into clinical workflows.

IBMs Watson Health is also working on the AI genomics initiative with Illumina.

Our mission is to improve human health through sequencing at a massive scale. The first human genome sequenced ten years ago, took years and cost $3 billion, said Chikarmane. We can sequence in less than a day and with our latest instrument it already costs less than $1K. We are now on our way to the $100 genome.

After the briefing, Chikarmane told Digital Health News that he could see the price of DNA sequencing falling below $100 in the future.

We all know the potential is tremendous, barriers of time and cost have been overcome.

But to make it mainstream we have to be able to analyse the data to identify mutations that can be treated, and identify the most effective drugs that can be used to treat patients. And this has to happen in the electronic medical record.

The ability to analyse the tsunami of genomics data generated is now the greatest barrier to progress, he said.

To interpret the vast amounts of genomics data today requires sophisticated, highly trained bioinformatics specialists.

Its the clinical back end and interpretation that is the limiting factor and thats where AI has such potential.

It can currently take 15 hours of a geneticists time to interpret one patient DNA sequence, Chikarmane said.

This is why it has been the realm of academics so far, using very highly trained geneticists, clearly this is not scalable how do you bring it to community hospitals? How do you make mainstream? You have to use AI.

Chikarmane said that genomics has to become embedded in clinical workflows if uptake was to move out of research labs.

To be mainstream genomics has to be at the point of care and with radiology and pathology reports.

Back in England, Genomics sequencing in the NHS has been supported through 100k Genome project. In 2014 the Government announced 300 million funding to support 11 Genome centres, which would be expected to sequence 10,000 genome by 2017.

That target was later pushed back to 2018.

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Genomics to hit mainstream with AI and $100 genome – Digital Health

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Genome studies point to common disease mechanisms in cardiovascular and other diseases – Science Daily

Posted: at 12:48 pm

Genome studies point to common disease mechanisms in cardiovascular and other diseases
Science Daily
The human genome has about 3.26 billion building blocks. Searching for variations relevant to the disease therein is like the famous search for a needle in a haystack. In genome-wide association studies (GWAS), researchers focus on typical variations

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Genome studies point to common disease mechanisms in cardiovascular and other diseases – Science Daily

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