Monthly Archives: June 2017

February 6, 2013 A paper describing the unified Os-Nipponbare-Reference-IRGSP-1.0 pseudomolecules and MSU Rice Genome Annotation Project Release 7 has been published.

February 7, 2012 The GFF3 and brief info files were updated on the FTP site. The update corrects issues with the UTR feature type and several cases where the mRNA coordinates were incorrect. The sequence files and other features in the GFF3 files were not changed.

October 31, 2011 Release 7 of the MSU Rice Genome Annotation Project is available. This release is based on a new pseudomolecule assembly (Os-Nipponbare-Reference-IRGSP-1.0) made in collaboration with the Agrogenomics Research Center at the National Institute of Agrobiological Sciences, Tsukuba, Japan. This set of pseudomolecules unifies the previous MSU with the IRGSP/RAP effort. Genome browser has been updated with 81 tracks of data. Orthologous group analysis has been updated to include Zea mays release 5b filtered gene models.

We have planned server maintenance on the first Wednesday of every month. The Rice Genome Annotation Project web pages may be unavailable or only partially functional during server maintenance.

Feb 6, 2013 - A paper describing the unified Os-Nipponbare-Reference-IRGSP-1.0 pseudomolecules and MSU Rice Genome Annotation Project Release 7 has been published in the journal Rice.

The MSU Rice Genome Annotation Project Database and Resource is a National Science Foundation project and provides sequence and annotation data for the rice genome.

This website provides genome sequence from the Nipponbare subspecies of rice and annotation of the 12 rice chromosomes. These data are available through search pages and our Genome Browser that provides an integrated display of annotation data.

In cooperation with researchers at the Agrogenomics Research Center at the National Institute of Agrobiological Sciences, Tsukuba, Japan, we have prepared a final assembly of the rice pseudomolecules. These pseudomolecule sequences are now common to both the MSU Rice Genome Annotation Project and the Rice Annotation Project Database (RAP-DB)/International Rice Genome Sequencing Project. This effort was undertaken in order to allow researchers to easily compare annotations from both the MSU and RAP-DB projects. Gene loci, gene models and associated annotations created by MSU-RAP and RAP-DB were independently derived, but the pseudomolecules used by the two rice annotation projects to generated those annotations are now identical and can be easily compared. A manuscript describing the generation of the final rice pseudomolecule assembly is in preparation.

While many researchers utilize the MSU loci, gene models and transcripts in their own databases and genome browsers, these sites may have outdated annotation and may have modified or further annotated our official gene set. All MSU rice gene names are of the form LOC_Os##g##### as explained on our nomenclature page. MSU rice genes are created using de novo gene predictions from Fgenesh followed by improvements and/or modifications by the PASA program which uses other de novo gene prediction software and rice full length cDNA and EST alignments. Our gene set is constructed entirely "in house" and is not equivalent to annotation from RefSeq, RAP, SwissProt or UniProt. Because we can not guarantee that data that is labeled as MSU/TIGR genes at other websites are really our data, we suggest that users always refer back to the MSU Rice Genome Annotation Project for our genuine and current MSU rice gene data. Please note that while we can not prevent users from downloading our entire Genome Browser, we do not sponsor or approve of public re-display of our rice genome browser.

Researchers who wish to cite the Rice Genome Annotation Project website are encouraged to refer to our recent publication:

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Rice Genome Annotation Project

In case you havent already heard of CRISPR-Cas9, it is the revolutionary gene-editing technology, discovered just a few years ago, that allows scientists to edit the DNA of any species with an unprecedented precision and efficiency. Today, thousands of researchers around the world are doing experiments with CRISPR, in the hope to cure us from genetic diseases and even deliver us designer babies. The first clinical trial to employ CRISPR-Cas9 is now underway in China, hoping to fight targeted cancers with modified immune cells.

The gene-editing method is based on the protective mechanism of bacteria against viruses. An RNA molecule carries segments of DNA from a previously encountered virus together with an enzyme (Cas9). Once the molecule encounters that same sequence of DNA, the enzyme gets activated and cuts it out. Researchers discovered that they can use this system to cut any DNA sequence at a precisely chosen location.

While the tool is touted for its precision, it is far from error free. Mutations do occur around the areas where the DNA has been cut and needs to be repaired. And sometimes CRISPR may hit unintended parts of the genome. Computer algorithms identify the most likely areas for these off-target mutations, which are later examined by researchers for deletions and insertions. However, whole-genome sequencing (WGS) - examining the entire DNA of living animals that had undergone gene editing - hadn't been done.

In a recently published study in the journal Nature Methods, titled Unexpected mutations after CRISPRCas9 editing in vivo scientists used whole-genome sequencing to study the mutations that had occurred in the DNA of mice that had undergone CRISPR gene editing.

Genetic Engineering and Biotechnology News reports that the investigators were able to determine that CRISPR had successfully corrected a gene that causes blindness, but found that the genomes of two independent gene therapy recipients had sustained more than 1500 single-nucleotide mutations and more than 100 larger deletions and insertions. None of these DNA mutations were predicted by computer algorithms that are widely used by researchers to look for off-target effects.

Co-author of the study Vinit Mahajan, M.D., Ph.D. said:

"We're still upbeat about CRISPR, we're physicians, and we know that every new therapy has some potential side effectsbut we need to be aware of what they are."

The authors are encouraging scientists to use the WGS method to determine all off-target effects of their CRISPR experiments.

In the last few days, however, some scientists have raised concerns about the validity of the study, questioning its methodology. Dr Gaetan Burgio, Group leader and head of the transgenesis facility at the Australian National University said in a Journal club review of the paper:

The claims over this paper are unsurprising as Cas9 enzyme could remain in the cells for days and create random indels in the genome. However, the main issues for me resides in the overestimation of the number of off target effects due to the lack of rigor in the experimental design to detect these unexpected mutations. In short my main point is these unintended mutation are likely to have preexisted prior to the injection of CRISPR system.

One thing is sure there is a lot more work to be done to ensure the safety of the CRISPR/Cas9 technology.

Photo Credit:Pixabay

See more here:
CRISPR May Cause Hundreds of Unintended Mutations Into the ... - Big Think

The last podcast in this series looks at current opportunities presented by advancements in Precision Medicine. How are healthcare organizations and patients learning to leverage the knowledge locked in our genes? And how can this knowledge become a real opportunity today?

Join Jennifer Girka, healthcare strategist within Dell EMCs Healthcare & Life Sciences division, as she provides an introduction to precision medicine. Girka is responsible for providing strategic insight to help Dell EMC advance its support of healthcare organizations, medical professionals and patients as they transform healthcare into the digital era. With more than 20 years helping to advance the healthcare industry with new opportunities and emerging technology, she works closely with healthcare customers and practitioners to bring them the right mix of technology innovation and solutions that will help them navigate through the ever-changing and increasingly complex world of healthcare.

Sources: To Adopt Precision Medicine, Redesign Clinical Care." NEJM Catalyst. February 5, 2017.http://catalyst.nejm.org/adopt-precision-medicine-personalized-health/ "Partners Data Lake Offers Healthcare Analytics as a Service." Health IT Analytics. March 17, 2016.http://healthitanalytics.com/news/partners-data-lake-offers-healthcare-analytics-as-a-service "Personalized Health Planning in Primary Care Settings." Fed Pract. 2016 January;33(1):27-34.http://www.mdedge.com/fedprac/article/105690/personalized-health-planning-primary-care-settings/page/0/1 Alice Park. "A Powerful New Tool for Editing the Human Genome." Time Magazine. April 4, 2016.http://time.com/4207612/a-scientist-gets-the-green-light-to-edit-the-human-genome/ City of Hope and Translational Genomics Research Institute combine to advance precision medicine and speed translational research.https://www.tgen.org/home/news/2016-media-releases/tgen-forges-alliance-with-city-of-hope.aspx#.WP9Y0dLyvIU

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The genome is out of the bottle: Embrace the possibilities - Healthcare IT News

When the 2015/2016 Zika virus epidemic swept through the Americas and several islands in the Pacific and Southeast Asia, researchers were urged to focus their efforts on developing treatments and vaccines to combat the virus effects.

A team of researchers from the Center for Genome Architecture at Baylor College of Medicine coincidentally had crucial but fragmented pieces of relevant data from previous research that could greatly impact this effort. Using a 3-D genome assembly approach referred to as HI-C, the team was able to quickly assemble the 1.2 billion letter genome of Aedes aegypti, the Zika-carrying mosquito, producing the first end-to-end assembly of each of its three chromosomes.

When the Aedes mosquito came into the spotlight in relation to the Zika epidemic, we found ourselves sitting on a bunch of relevant data and proof-of-principle work, said Olga Dudchenko, a postdoctoral fellow at The Center for Genome Architecture. The situation prompted us to polish our methods and share the data we had.

The development provides a much-needed boost to research and treatment options for the Zika virus by identifying vulnerabilities in the mosquito that the virus uses to spread.

With the success of assembling the Aedes genome, the Baylor team has also shown that the 3-D assembly technique can be an important tool for similar outbreaks in the future, and could also aid in personalized care for human patients suffering from a variety of diseases.

Timeline Erez Lieberman Aiden, Director of the Center for Genome Architecture, originally proposed the general idea of 3-D assembly in 2009. Lieberman Aiden and colleagues first tested their technique in 2013 by sequencing a human genome, and comparing the data to that made available by the Human Genome Project.

The team found their assembly correlated with the reference data from the Human Genome Project with 99 percent accuracy, validating the method. However, the 3-D assembly method produced similar results in a fraction of the time, and at significantly less cost.

They then switched their focus toward the Aedes aegypti mosquito, which is responsible for the spread of not only Zika virus, but dengue, chikungunya and yellow fever. When the Zika outbreak began to become a global health threat, the team knew they could piece together information they acquired from previous research to create a clear, cohesive picture of the mosquitos genome.

3-D assembly allowed the team to create the 1.2 billion-letter genome of the mosquito for about $10,000a price comparable to that of an MRI scan. The third phase of their research included assembling the genome of the Culex quinquefasciatus mosquito, a carrier of West Nile virus.

Culex is another important genome to have since it is responsible for transmitting so many diseases, said Lieberman Aiden. Still, trying to guess what genome is going to be critical ahead of time is not a good plan. Instead, we need to be able to respond quickly to unexpected events. Whether it is a patient with a medical emergency or the outbreak of an epidemic, these methods will allow us to assemble de novo genomes in days, instead of years.

For the Culex sequence, the researchers carried out their work with IBMs VOLTRONa high performance computing (HPC) system. VOLTRON is based on the companys Power Systems platform, which provides scalable HPC capabilities necessary to accommodate a broad spectrum of data-enabled research activities. The Power Systems platform has also been selected for use by the Department of Energys Oak Ridge and Lawrence Livermore National Laboratories, and the UK governments Science and Technology Facilities Councils Hartree Centre.

3-D assembly and IBM technology are a terrific combination: one requires extraordinary computational firepower, which the other provides, said Lieberman Aiden. Incorporated into the design of VOLTRON is a POWER and Tesla technology combination that allowed Baylor researchers to handle extreme amounts of data with incredible speed. VOLTRON comprises a cluster of four systems, each featuring a set of eight NVIDIA Tesla GPUs tuned by NVIDIA engineers to help Baylors researchers achieve optimum performance on their data-intensive genomic research computations.

The team also made a new discovery about these mosquito families during sequencing. They found that chromosome content did not mix much across the species, which could prove helpful in any future outbreak with a mosquito as a carrier, regardless of whether its genome is sequenced or not.

If youre looking at various mammals, chromosome content will mix a lot from one species to another. But what turned out to happen in mosquitoes was a very different story. What we saw is that although things mix a lot locally, (within chromosome arms) very little content jumped from one arm to another, or from one chromosome to another chromosome, explained Dudchenko.

This fundamental fact of mosquito evolution offers immediate benefit for researchers. If another epidemic hit through a completely different mosquito carrier that researchers and health officials know nothing about, they can at least infer where to look for particular genes or targets within the new carrier because of this unique property. In the event of a new outbreak, this technology could answer questions much faster and lead to the rapid development of a treatment or vaccine, saving lives and money.

Advancing capabilities As Dudchenko explained to Laboratory Equipment, the field of genome assembly is a very actively developing field, providing researchers with genetic information that was previously unobtainable.

But for certain applications, assembly methods can be suboptimal.

Prior to the 3-D genome assembly method, it was challenging and extremely expensive to sequence a genome by starting at the beginning of a chromosome and reading all the way through to the end. Instead, researchers would use methods that read small snippets of chromosomes many times over, find overlaps in those snippets and piece them together to create longer, continuous sequences.

The problem arises, however, when repetitive fragments appear, or theres a large amount of variation across a species.

Its like reading a book in which the pages arent bound or numbered in any meaningful way, Dudchenko said. In some sense, the information is all there and if youre lucky enough that the information you want to read off is in the paragraph on the same page, you can make sense of it. But if you have longer stretches of text, or are unlucky and hit the end of the page, you dont know where to go from there, and theres not a lot you can do with this information.

Another problem with short-reads or jumping methods is when DNA is being extracted, the chromosomes rarely remain unbroken.

But HI-C provides the needed information at the scale of whole chromosomes.

The technique traces the genome as it folds inside the nucleus, and shows how frequently different stretches of the genome come into contact with each other. This enabled the team to stitch together hundreds of millions of short DNA reads into the sequences of entire chromosomes.

People can view HI-C as a type of jumping library that spans all scales, said Dudchenko.

Clinical relevance The short-read format also greatly reduces the cost of assembly, making it an option for doctors to conduct a personalized genome project on individual patients as needed.

This is the technology that will get you there, said Dudchenko.

Prior to HI-C, a clinician may sequence a persons DNA, but instead of fully assembling it, they align it with a reference and look for typos to see where the patient differs from the genome reference. The disadvantage with this approach is that the clinician is looking at someones genome through the lens of an existing reference, creating a biased view. It relies heavily on prior work, and if theres something unexpectedly different, the clinician may not notice, according to Dudchenko.

The next step for the Baylor team is to build more of a stable infrastructure for other research groups to utilize the HI-C technology in their respective fields, and to make it more straight-forward for people who may not necessarily come from a 3-D space with relevant expertise.

Were very excited to see how this technology will play out with different genes and assemblies, and how far we will be able to go with this technology, added Dudchenko. Right now, were pretty optimistic.

More here:
Assembling Genomes from Scratch, at a Fraction of the Cost - Laboratory Equipment

A study of 124 advanced breast, lung and prostate cancer patients demonstrated that a new, high-intensity genomic sequencing approach can detect circulating tumor DNA at a high rate.

In the study, which was presented at the 2017 American Society of Clinical Oncology (ASCO) Annual Meeting, 89 percent of the patients had at least one genetic change detected in the tumor that was also detected in the blood.

Also, 627 genetic changes found in tumor samples were also found in blood samples using this new approach.

Our findings show that high-intensity circulating tumor DNA sequencing is possible and may provide invaluable information for clinical decision-making, potentially without any need for tumor tissue samples, lead study author Dr. Pedram Razavi, Ph.D., a medical oncologist and instructor in medicine at Memorial Sloan Kettering Cancer Center, said in a statement. This study is also an important step in the process of developing blood tests for early detection of cancer.

Razavi said the approach is not intended to be commercially available to patients and the researchers will now use the technology to potentially develop a blood test for early cancer detection.

The researchers used a combination of breadth and depth by scanning a very broad area of the genome508 genes and more than two million base pairs or letters of the genomewith high accuracy, yielding about 100 times more data than other sequencing approaches.

In liquid biopsies, including commercial tests, only a relatively small portion of the genome are profiled. Those tests are also only used on patients already diagnosed with cancer in order to help monitor the disease or detect actionable alterations that can be matched to available drugs or clinical trials.

The researchers analyzed tumor tissues using MSK-IMPACTa 410-gene diagnostic test that provides detailed genetic information about a patients cancer. They also separated the plasma in blood cells and extracted cell-free DNA from the plasmas and separately sequenced the genome of white blood cells using the high-intensity, 508-gene sequencing assay.

Finding tumor DNA in the blood is like looking for a needle in a haystack. For every 100 DNA fragments, only one may come from the tumor and the rest may come from normal cells, mainly bone marrow cells, Razavi said. Our combined analysis of cell-free DNA and white blood cell DNA allows for identification of tumor DNA with much higher sensitivity, and deep sequencing also helps us find those rare tumor DNA fragments.

The test detected at least one genetic change in the tumor and the blood in 97 percent of the breast cancer patients, 85 percent of the lung cancer patients and 84 percent of the prostate cancer patients.

Prior research in the field has primarily focused on using knowledge from tumor tissue sequencing to identify specific changes to look for in circulating tumor DNA, Razavi said. This approach allows us to detect, with high confidence, changes in circulating tumor DNA across a large part of the genome without information from tumor tissue.

See the article here:
ASCO 2017: Genomic Sequencing Approach Step Toward Early Cancer Detection - R & D Magazine