Daily Archives: May 9, 2017

About CGD

This is the home of the Candida Genome Database, a resource for genomic sequence data and gene and protein information for Candida albicans and related species. CGD is based on the Saccharomyces Genome Database and is funded by the National Institute of Dental & Craniofacial Research at the US National Institutes of Health.

JBrowse can be launched from any CGD feature's Locus Summary Page by clicking on the JBrowse logo about halfway down the page: The JBrowse window will be centered upon that feature.

Alternately, mouse-over "JBrowse" on the top menu bar of any CGD page, then select and click your organism of interest in the drop-down menu. The browser window will be centered on an arbitrary location of the genome.

Please see our JBrowse Help Page for more details. (Posted September 29, 2016)

Taking advantage of next-generation sequencing and achieving nearly 700-fold coverage, this phased, diploid assembly permits more sensitive, allele-specific analysis of the genome structure and funcion. A22 supersedes the previous Assembly 21 as the default genome sequence for C. albicans SC5314. All the previous assemblies remain available at CGD's download pages. (Posted June 27, 2014)

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Candida Genome Database

Yeast grow on an agar plate in the form of the microbes chromosomes, with colors representing whether a chromosome exists in a synthetic form (yellow) or just wild-type (orange).

Drew Gurian

By Ryan CrossMay. 8, 2017 , 2:15 PM

Tuesday morning, more than 200 biologists, businesspeople, and ethicists will converge on the New York Genome Center in New York City to jump-start what they hope will be biologys next blockbuster: Genome Project-write (GP-write), a still-unfunded sequel to the Human Genome Project where instead of reading a human genome, scientists create one from scratch and incorporate it into cells for various research and medical purposes. For example, proponents suggest that they could design a synthetic genome to make human cells resistant to viral infections, radiation, and cancer. Those cells could be used immediately for industrial drug production. With additional genome tinkering to avoid rejection by the immune system, they could be used clinically as a universal stem cell therapy.

The project got off to a bumpy start last year and despite the central rallying cry of a synthetic human genome, many of those attending the conference will bring in different expectations and ambitions. Some resent the unwanted attention and criticism that the projects public objective has brought, saying it distracts from the goal of improving DNA synthesis technologies, because cheaper and faster methods to write DNA have many applications in applied and basic research. Others say that a made-to-order human genome is inevitable anyway, hoping to seize the publicity and controversy it creates as an opportunity to educate the public about synthetic biology.

If you put humans as the target, even though you are not going to make a human baby, it will be provocative, it will be misinterpreted, but people will engage, says Andrew Hessel, a self-described futurist and biotechnology catalyst at Autodesk in San Francisco, California, a successful software company that specializes in 3D design programs for architecture and other fields that has been exploring synthetic biology applications in recent years. Hessel is one of the four founders of GP-write, along with lawyer Nancy Kelley and geneticists Jef Boeke of New York University Langone Medical Center in New York City and George Church of Harvard University.

GP-write debuted prematurely in May 2016, when an invitation-only meeting at Harvard became public and sparked a media firestorm about the lack of transparency for an initiative that to some people sounded like a plan to create genetically enhanced humansthe leaders say it isnt, although Church wasnt shy when musing aboutdesigner humans in a 2012 book he authored. The intent of the closed-door meeting was to allow scientists to speak freely, Hessel and the other leaders say, and to prepare a peer-reviewed paper describing the project that was later published in Science in June. The month gap between the meeting and the Science paper created further confusion because the papers embargo forbade scientists from discussing the project.

GP-writes founders hope that this weeks open meeting will reinforce the seriousness of the initiative. Ethicists and lawyers are now sprinkled throughout the groups many nooks, and several young biotech startups and software developers have expressed interest in GP-write. Scientists are also encouraged to propose their own pilot projects to serve as stepping stones, although many participants are careful to note that these projects are valuable regardless of whether the group decides to reach for the ultimate goal of synthesizing a human genome.

There is definitely an internal tension among GP-writes supporters, Hessel says. Scientists are a conservative community.

Hessel first proposed a vision to synthesize a human genome in a Huffington Post article back in 2012. Several years later, during an international conference about synthesizing the yeast genome in 2015, Hessel reiterated the goal in a panel discussion, saying it should be biologys next big science effort. Frankly, I was surprised that the scientific community hadnt organized to suggest something like this, Hessel says. It just seemed kind of obvious and I think it stunned the crowd.

A week later, Hessel called Church and asked whetherhe would be open to leading the initiative. Church agreed, providedBoeke, the leader of the international synthetic yeast project Sc2.0, came aboard as a co-leader. Boeke took a bit more convincing. My immediate reaction was, Oh my gosh, you have got to be kidding me, Boeke says. I am definitely the conservative of the group.

But then he was persuaded that some of the pilot goals of the project were worthwhile. I got most excited about it when George brought his idea of virus-resistant mammalian cells on the table, and the idea of an ultrasafe cell line, which could be a relatively short-term win, Boeke says. Engineering an ultrasafe cell line would be a boon to biotechnology companies that use large vats of cells to crank out biologic drugs or industrial molecules. They now must constantly monitor for signs of a viral infection that could wipe out tanks of cells across an entire manufacturing facility.

The synthetic biology effort was originally called Human Genome Project 2, but the founders changed the name to Human Genome Project-write by the time of the closed-door meeting last May. Since then, they dropped human in an attempt to diffuse public controversies. The human part of it really got a lot of people overly excited, and that kind of overshadowed the intent to make it be about writing genomic sequences in general, Boeke says. Both George Church and I from the very beginning always envisioned this as not being limited to humans. That expanded vision is particularly apparent in this weeks meeting, which will include talks from scientists working with genomes from species as varied as bacteria, yeast, octopuses, and plants.

But despite the carefully crafted allusion to the Human Genome Project, which garnered about $3 billionin financial support from government and industry, GP-write, for now, doesnt have any money to offer researchers. We hope the [National Institutes of Health] will be involved in GP-write but thus far they havent been as enthusiastic as we are, Boeke says.

GP-writes current funding is a far cry from the $100 million they hoped to raise in 2016. Last year, Autodesk contributed $250,000 to GP-write to kick-start planning and organization. The next round of funding may come from Labcyte, a firm specializing in machines that manipulate miniscule amounts of liquid through ultrasound.According to a meeting organizer, Labcyte will be GP-writes first corporate partner. The company confirms it has made a 3-year financial commitment, but has not disclosed the terms yet.

So far, scientists hoping to be part of GP-write are pursuing synthetic biology pilot projects with funding theyve gotten independently. Harris Wang of Columbia University told ScienceInsider that he will receive $500,000 from the Defense Advanced Research Projects Agency (DARPA) to engineer about 40 nonhuman metabolic genes into human cells, enabling them to produce the nine essential amino acids that we now must get from our diet. A small tech company called Chromologic received $200,000 from DARPA to study methods for shuttling large strands of synthetic DNA into cells, although this project was not explicitly related to GP-write. And early stage startup Neochromosome, which includes Boeke, intends to raise money to design synthetic chromosomes for medicine that could be used in an off-the-shelf universal cell line in cell therapies and transplants with minimal risk of rejection from the immune system.

Technical feasibility aside, an undertaking right now to synthesize a complete human genome would be extraordinarily expensiveeasily upwardof $100 million with current pricing. The human genome is 3 billion nucleotides long. Thats a million times bigger than the longest piece [of DNA] we make today, says Emily Leproust, CEO of Twist Bioscience in San Francisco. Her company has developed a faster, higher-throughput method to assemble DNA for about $0.09per base compared witha previous average of $0.25, she says. And although companies like Twist could stand to benefit from large orders of DNA from GP-write, she notes that to do the kind of science that the GP-write is talking about, there needs to be a massive technology improvement.

One young startup, Molecular Assemblies in San Diego, California, has rejected the decades-old organic chemistry method of linking DNA bases. Instead, they are refining a new method that utilizes a little-studied DNA-making enzyme found in some cells. The company anticipates going commercial within 2 to 3 years with a process using a template independent polymerasean unusual enzyme that, unlike most polymerases, synthesizes DNA without having a strand whose sequence can be copied. Our nascent company motto is that we think DNA will be the industrial polymer of the 21st century, chief scientific officer Bill Efcavitch says. Beyond the numerous synthetic biology applications, Efcavitch envisions that cheaper and more rapid DNA synthesis will push innovation in nanotechnology applications, such as using DNA for biosensors and data storage.

There is lots of good science going on, but it is initiated and funded outside GP-write, because there is no funding yet, says Seattle, Washingtonbased biotech investor Robert Carlson, an author of the GP-write paper published in Science. You can conceive of this meeting as some people gathering around a beer or a whiteboard and saying, 'Lets lay out some experiments to test some ideas about how genomes are put together and why they are organized the way they are.'

Whetherthe project develops financial legs to carry out its goals remains to be seen, but at the very least, it is recruiting a passionate, if not fully unified, group. At the end of the day, it is really about putting the foundation in place to write much larger genomes than we are presently able to, and to recognize that these technologies are coming very quickly whether we are ready for them or not, Hessel says. I think this is just going to be a kickass meeting. The room is going to be full of interesting folks. And I am sure there will be dissenters too.

Correction, 6:25 P.M. This story has been changed to clarify that no specific announcement regarding Labcyte's funding is planned for the New York meeting.

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Money still missing as the plan to synthesize a human genome takes ... - Science Magazine

Science Daily

New and improved genome sequence of Daphnia pulex Science Daily Researchers have completed a new and improved genome sequence of Daphnia pulex (D. pulex), providing a clearer roadmap of the organism's genome so they can identify the genes and pathways that make this organism so successful in freshwater ... and more »

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New and improved genome sequence of Daphnia pulex - Science Daily

According to the National Human Genome Research Institute, about 300 different species have had their entire genomes sequenced. Us, obviously, but also rats, puffer fish, fruit flies, sea squirts, roundworms, chickens, dogs, yeast, honey bees, gorillas, chimpanzees, sea urchins, a bunch of bacteria, and many assorted other birds, plants, animals, and fungi.

New to the list is the orb-weaver spider Nephila clavipes. Analysis of this spiders genome hints at how spider silk evolved, helping us to understand the whole system better and bringing us that much closer to our ultimate goal of one day making super-strong spider silk to achieve our own ends. (Mwhahahaha...)

Orb weavers, the kind that weave circular webs, comprise the third largest family of spiders: about 3,000 species. Each female orb weaver can produce different kinds of silk in her different kinds of silk glands. The silk used for draglines, bridges, and web radii has great tensile strength.The silk used for prey wrapping and egg-case insulation is strong yet flexible. The silk used for prey capture is sticky and viscous.

Spider silks can be stronger than steel and tougher than Kevlar, in the words of the University of Pennsylvania researchers who just reported the new genome, yet are much lighter weight than these manmade materials. They can conduct electricity, are resilient to temperature fluctuations, have antibiotic properties, and are undetectable by our immune system. Hence our desire to figure out how to make them, for future medical and industrial uses.

Spider silks are made of proteins called spidroins, for spider fibroins. The orb weavers genome provides the first compilation of all the spidroins in a given species, and it offers some surprises. First off, the genome includes eight as-yet-unreported spidroins fora total of 28.

Historically, as spidroins were discovered, they were named after the particular silk gland in which they were first found. But looking at gene expressionrevealed that each silk gland produced spidroins formore than one type of silk, and sometimes spidroins showed up in glands distinct from their namesakes.

One of the novel spidroins was expressed exclusively in venom glands, suggesting that it may have a function beyond silk-related applications. Much like spider silk, spider venom is a complicated mixture of proteins. The production of both are ancient and defining characteristics of orb-weaving spiders.

Spidroins have a shared beginning and end, but vary in the middle. The middle of the protein is comprised of pieces from a set of400 different motifs. Each spidroin contains a different combination of these motifs mixed and matched in different orders and with different frequencies, and this variation confers their specific and different physical properties. This observation lends credence to the idea that the spidroin genes evolved by means of tandem duplication events, wherein these motifs got copied.

And the beginnings and ends of the molecules, while similar enough to stay recognizable, are more variablethan most other genes. These two propertiesa hypervariable middle section sandwiched between two moderately variableregionsmake for a highly plastic protein molecule that can evolvefairly rapidly.The researchers suggestthat the spidroin gene family is still evolving, meaning wed probably learn more by looking through the genomes of some more spiders.

Nature Genetics, 2017. DOI: 10.1038/ng.3852 (About DOIs).

This post originated on Ars Technica

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Spider genome reveals new genes and proteins involved in silk production - Ars Technica UK

A new study in Science from Karolinska Institutet maps out how different DNA-binding proteins in human cells react to certain biochemical modifications of the DNA molecule. The scientists report that some master regulatory proteins can activate regions of the genome that are normally inactive due to epigenetic changes. Their findings contribute to a better understanding of gene regulation, embryonic development and the processes leading to diseases such as cancer.

The DNA molecule carries information in the form of a sequence of four nucleotide bases, adenine (A), cytosine (C), guanine (G) and thymine (T), which can be thought of as the letters of the genomic language. Short sequences of the letters form DNA words that determine when and where proteins are made in the body.

Almost all of the cells in the human body contain the letters in precisely the same order. Different genes are however active (expressed) in different cell types, allowing the cells to function in their specialised roles, for example as a brain cell or a muscle cell. The key to this gene regulation lies in specialised DNA-binding proteins transcription factors that bind to the sequences and activate or repress gene activity.

Two variants of the same letter

The DNA letter C exists in two forms, cytosine and methylcytosine, which can be thought of as the same letter with and without an accent (C and ). Methylation of DNA bases is a type of epigenetic modification, a biochemical change in the genome that does not alter the DNA sequence. The two variants of C have no effect on the kind of proteins that can be made, but they can have a major influence on when and where the proteins are produced. Previous research has shown that genomic regions where C is methylated are commonly inactive, and that many transcription factors are unable to bind to sequences that contain the methylated .

By analysing hundreds of different human transcription factors, researchers at Karolinska Institutet in Sweden have now found that certain transcription factors actually prefer the methylated . These include transcription factors that are important in embryonic development, and for the development of prostate and colorectal cancers.

The results suggest that such master regulatory factors could activate regions of the genome that are normally inactive, leading to the formation of organs during development, or the initiation of pathological changes in cells that lead to diseases such as cancer, says Professor Jussi Taipale at Karolinska Institutets Department of Medical Biochemistry and Biophysics who led the research.

Helps us interpret the genetic language

The results pave the way for cracking the genetic code that controls the expression of genes, and will have broad implications for the understanding of development and disease. The availability of genomic information relevant to disease is expanding at an exponentially increasing rate.

This study identifies how the modification of the DNA structure affects the binding of transcription factors, and this increases our understanding of how genes are regulated in cells and further aids us in deciphering the grammar written into DNA, says Professor Taipale.

Reference

Yin, Y., Morgunova, E., Jolma, A., Kaasinen, E., Sahu, B., Khund-Sayeed, S., . . . Taipale, J. (2017). Impact of cytosine methylation on DNA binding specificities of human transcription factors. Science, 356(6337). doi:10.1126/science.aaj2239

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Understanding the Language of the Genome - Technology Networks

Xconomy San Diego

San Diegos Edico Genome, highlighted in Mondays media debut of Dell Technologies Capital, said today it has raised $22 million in Series B financing led by the Dell investment arm. All existing investors, including Qualcomm Ventures, Axon Ventures, and biotech industry executive Greg Lucier, participated in the round.

The new cash, which brings Edicos total funding to $32 million, will be used to fuel expansion and further development of Edicos Dragen technology. Theres a lot of additional engineering and software development that needs to be done, and Edico also plans to expand its sales and marketing team, CEO Pieter van Rooyen said yesterday. He expects the company will grow from 50 employees to close to 60 by the end of the year.

In 2014, Edico introduced its Dragen processor on a standard computer expansion bus (similar to a graphics processing card) as a combination of hardware and software that was optimized for genomics data processing. The Edico chip, a field-programmable gate array (FPGA), was intended to accelerate the process of reading sequenced nucleotidesA, C, T, or Gfrom the short DNA segments produced by high-throughput sequencing, and to align them with a reference genome. Its a computationally intensive process referred to as genome mapping that Edico has reduced from 20 hours to 20 minutes.

The company sells its technology to high-throughput genome sequencing centers, academic research institutions, and clinical labs, accelerating the processing time for clinical diagnoses and scientific insights. Edico says its customers have cumulatively processed more than 12 petabytes of genomic data. (If a byte of data was a single grain of rice, Edico says one petabyte would be enough rice to blanket Manhattan.)

Edico also has established technology partnerships with Dell EMC, Intel, IBM, Amazon Web Services, and others to develop cloud-based services for analyzing and storing genomic data. Under this software-as-a-service model, van Rooyen said, We get paid for the number of DNA petabases that get sequenced.

Bruce V. Bigelow is the editor of Xconomy San Diego. You can e-mail him at bbigelow@xconomy.com or call (619) 669-8788

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Edico Genome Raises $22M to Expand Data Processing and Web Services - Xconomy

To begin where the last post ended In none of this literature is Adam everyman, any more than Eve is every woman though there are some hints in the latter direction in Sirach.

What is in any case assumed in all these intertestamental reflections is that Genesis is telling a historical story about real people who affected not only themselves but their descendants in various ways. They are not merely literary figures who set bad examples for those who read their stories. It is thus not helpful to say no author cared about giving Adam a historical reading (p. 168). None of these authors defended the historicity of Adam because it was not a question or an issue, nor did any of them view the historical Adam in light of later Christian tradition. This is however very different from saying none of them thought Adam was a historical= real person in space and time. In fact, none of them would have spoken of Adam as they do in regard to genealogies and effects on descendants if they did not take it for granted that he and Eve were real persons. And finally, at Qumran the story is the same. CD 10.8; 4Q504; 4 Q167 1 QS 3-4 depict an Adam who is the first breaker of faith with God, the first breaker of the covenant, the first formed in, and the first to deform the image of God, and so on.

Yes, the later full form of the Christian analysis of Adam by Augustine and subsequent interpreters is not found in these texts, and doubtless some of those interpreters went not just beyond but against what the Bible says, and need correction. This however doesnt mean that anyone in the Biblical and intertestamental tradition thought Adam and Eve were mere literary figures, or ciphers for everyone, but not real ancestors of Gods people.

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Adam and the Genome Part Twenty Three - Patheos (blog)

Yeast is a familiar microbe that enabled early societies to brew beer and leaven bread and empowers modern ones to synthesize biofuels and conduct key biomedical research. Yeast remains a vital biological agent, yet researchers' ability to explore and influence its genomic activity has lagged.

In an article in Nature Communications, University of Illinois researchers describe how their successful integration of several cutting-edge technologies the creation of standardized genetic components, implementation of customizable genome editing tools and large-scale automation of molecular biology laboratory tasks will enhance the ability to work with yeast.

The results of their new method demonstrate its potential to produce valuable novel strains of yeast for industrial use as well as to reveal a more sophisticated understanding of the yeast genome.

"The goal of the work was really to develop a genome-scale engineering tool for yeast. ... Traditional metabolic engineering focused on just a few genes, and the few existing genome-scale engineering tools are only applicable to bacteria, not eukaryotic organisms like yeast," said Huimin Zhao, the Steven L. Miller chair of chemical and biomolecular engineering at the University of Illinois, who led the study. "A second innovation is the use of synthetic biology concepts, the modularization of the parts and integration with a robotic system, so we can do it in high throughput."

The team focused on yeast, in part, because of its important modern-day applications; yeasts are used to convert the sugars of biomass feedstocks into biofuels such as ethanol and industrial chemicals such as lactic acid or to break down organic pollutants. Because yeast and other fungi are eukaryotes organisms with a compartmentalized cellular structure and complex mechanisms for control of their gene activity studying the yeast genome function is also a key component of biomedical research, they said.

"In basic science, a lot of fundamental eukaryotic biology is studied in yeast," said Tong Si, a Carl R. Woese Institute for Genomic Biology research fellow." People have a limited understanding of these complicated systems. Although there are approximately 6,000 genes in yeast, people probably know less than 1,000 by their functions; all the others, people do not know."

The group took the first step toward the goal of a novel engineering strategy for yeast by creating what is known as a cDNA library: a collection of more than 90% of the genes from the genome of baker's yeast (Saccharomyces cerevisiae), arranged within a custom segment of DNA so that each gene will be, in one version, overactive within a yeast cell and, in a second version, reduced in activity.

Zhao and colleagues examined the ability of the CRISPR-Cas system a set of molecules borrowed from a form of the immune system in bacteria. (CRISPR stands for clustered regularly interspaced short palindromic repeats, describing a feature of this system in bacterial genomes.) This system allowed Zhao to make precise cuts in the yeast genome, into which the standardized genetic parts from their library could be inserted.

"The first time we did this, in 2013, there was no CRISPR. ... The best we could get was 1% of the cells modified in one run," Si said. "We struggled a little on that, and when CRISPR came out, that worked. We got it to 70% (cells modified), so that was very important."

The gene activity-modulating parts integrating into the genome with such high efficiency allowed the researchers to randomly generate many different strains of yeast, each with its own unique set of modifications. These strains were subjected to artificial selection processes to identify those with desirable traits, such as the ability to survive exposure to reagents used in the biofuel production process.

This selection process was greatly aided by the Illinois Biological Foundry for Advanced Biomanufacturing (iBioFAB), a robotic system that performs most of the laboratory work described above in an automated way, including selection of promising yeast strains. Use of iBioFAB greatly accelerated the work by enabling simultaneous creation and testing of many unique strains.

With support from the university's High Performance Biological Computing Group, Zhao, Si and their colleagues analyzed the modified genomes of their most promising yeast strains. They identified combinations of genes whose altered activities contributed to desirable traits; the functions of some of these genes were previously unknown, demonstrating the technique's ability to generate new biological knowledge.

"I think the key difference between this method and the other existing metabolic engineering strategies in yeast is really the scale," Zhao said. "The current metabolic engineering strategies are all focused on just a few genes dozens of genes, at most; ... it's very intuitive. With this, we can explore all the genes; we can identify a lot of targets that cannot be intuited."

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New capabilities developed for genome-wide yeast manipulation - Feedstuffs