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The Limits of De Novo DNA Motif Discovery

The Limits of De Novo DNA Motif Discovery | SynBioFromLeukipposInstitute | Scoop.it

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Simcha D, Price ND, Geman D.

"A major challenge in molecular biology is reverse-engineering the cis-regulatory logic that plays a major role in the control of gene expression. This program includes searching through DNA sequences to identify "motifs" that serve as the binding sites for transcription factors or, more generally, are predictive of gene expression across cellular conditions. Several approaches have been proposed for de novo motif discovery-searching sequences without prior knowledge of binding sites or nucleotide patterns. However, unbiased validation is not straightforward. We consider two approaches to unbiased validation of discovered motifs: testing the statistical significance of a motif using a DNA "background" sequence model to represent the null hypothesis and measuring performance in predicting membership in gene clusters. We demonstrate that the background models typically used are "too null," resulting in overly optimistic assessments of significance, and argue that performance in predicting TF binding or expression patterns from DNA motifs should be assessed by held-out data, as in predictive learning. Applying this criterion to common motif discovery methods resulted in universally poor performance, although there is a marked improvement when motifs are statistically significant against real background sequences. Moreover, on synthetic data where "ground truth" is known, discriminative performance of all algorithms is far below the theoretical upper bound, with pronounced "over-fitting" in training. A key conclusion from this work is that the failure of de novo discovery approaches to accurately identify motifs is basically due to statistical intractability resulting from the fixed size of co-regulated gene clusters, and thus such failures do not necessarily provide evidence that unfound motifs are not active biologically. Consequently, the use of prior knowledge to enhance motif discovery is not just advantageous but necessary. An implementation of the LR and ALR algorithms is available at http://code.google.com/p/likelihood-ratio-motifs/."

http://1.usa.gov/UmVxkw

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Craig Venter: Health, Genomics, Research and Power

Biologist and entrepreneur Craig Venter discusses the intersection between health, genomics, research and power.

 

For the full 46 minute interview go to 

http://fora.tv/2012/10/16/Craig_Venter_Health_Genomics_Research_and_Power

 

More previews of Many other interviews from the October 15-16 Living by Numbers Health Conference by WIRED and the Robert Wood Johnson Foundation

http://fora.tv/conference/wired_health_conference_living_by_numbers

 

"a new conversation on the future of healthcare with 200 expert leaders from the worlds of medicine, science, technology, and business.

....a clear, compelling argument that today there is a new opportunity to bring data into real-time decision-making for doctors, researchers, hospitals, and individuals. This combination has the potential to transform people's lives.

.....spanning the gap between healthcare and technology, connecting pioneering researchers with ambitious entrepreneurs. First and foremost, .... a forum for ideas. Expect new connections, new opportunities, and new insights in how better data is driving us all toward better health."

 

The full interviews are here:

http://fora.tv/conference/wired_health_conference_living_by_numbers/buy_programs


Via AUNG THIHA, David Gifford
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Undergraduate Synthetic-Biology Contest Mixes Fun With Serious Warnings - Government - The Chronicle of Higher Education

Undergraduate Synthetic-Biology Contest Mixes Fun With Serious Warnings - Government - The Chronicle of Higher Education | SynBioFromLeukipposInstitute | Scoop.it
The range of projects at the International Genetically Engineered Machine meeting demonstrate the excitement and the anxiety inherent in the young discipline.
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The Role of Synthetic Biology for In Situ Resource Utilization (ISRU) | Abstract

The Role of Synthetic Biology for In Situ Resource Utilization (ISRU) | Abstract | SynBioFromLeukipposInstitute | Scoop.it

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Michael Montague, George H. McArthur Charles S. Cockell, Jason Held, William Marshall, Louis A. Sherman, Norman Wang, Wayne L. Nicholson, Daniel R. Tarjan, and John Cumbers

"A persistent presence in space can either be supported from Earth or generate the required resources for human survival from material already present in space, so called “in situ material.” Likely, many of these resources such as water or oxygen can best be liberated from in situ material by conventional physical and chemical processes. However, there is one critical resource required for human life that can only be produced in quantity by biological processes: high-protein food. Here, recent data concerning the materials available on the Moon and common asteroid types is reviewed with regard to the necessary materials to support the production of food from material in situ to those environments. These materials and their suitability as feedstock for the biological production of food are reviewed in a broad and general way such that terminology that is often a barrier to understanding such material by interdisciplinary readers is avoided. The waste products available as in situ materials for feasibility studies on the International Space Station are also briefly discussed. The conclusion is that food production in space environments from in situ material proven to exist there is quite feasible. ..."

http://bit.ly/TwGvun

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Bristol University | News from the University | Synthetic biology funding

Bristol University | News from the University | Synthetic biology funding | SynBioFromLeukipposInstitute | Scoop.it
Scientists from the University of Bristol have been awarded a £1.1 million share of the Biotechnology and Biological Sciences Research Council (BBSRC)'s strategic Longer and Larger Awards in Synthetic Biology, announced today.
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Undergraduate Competition Illuminates Promises and Perils of Synthetic Biology - Government - The Chronicle of Higher Education

Undergraduate Competition Illuminates Promises and Perils of Synthetic Biology - Government - The Chronicle of Higher Education | SynBioFromLeukipposInstitute | Scoop.it
The range of projects at the International Genetically Engineered Machine meeting demonstrate the excitement and the anxiety inherent in the young discipline.
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George Church and the potential of synthetic biology - O'Reilly Radar

George Church and the potential of synthetic biology - O'Reilly Radar | SynBioFromLeukipposInstitute | Scoop.it
A few weeks ago, I explained why I thought biohacking was one of the most important new trends in technology. If I didn't convince you, Derek Jacoby's review (below)...
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*SYNTHETIC BIOLOGY* *Let's start talking*

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Nicole Rusk

"Synthetic networks in mammalian cells can regulate cellular behavior."

http://bit.ly/PKwAmo

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One-stop shop for disease genes

One-stop shop for disease genes | SynBioFromLeukipposInstitute | Scoop.it

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Monya Baker

"When Heidi Rehm surveys a patient’s genes and finds a variant she’s never seen before, she improvises. First Rehm, who directs a clinical genetics testing laboratory at Partners HealthCare in Cambridge, Massachusetts, checks through as many as ten databases to learn whether that variant has ever been associated with disease. Then she may ask colleagues at other clinical sequencing laboratories whether they have seen it. But the launch this week of a database known as ClinVar will make her job much easier — and allow her to ask more sophisticated questions.

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Developed by the US National Institutes of Health (NIH) National Center for Biotechnology Information (NCBI) in Bethesda, Maryland, ClinVar integrates dozens of existing databases. It also provides, for the first time, a central place in which clinical testing laboratories can deposit their data, because most currently keep their data within the laboratory. By aggregating such information, ClinVar’s creators hope to accelerate clinicians’ understanding of the effects of variants as well as reveal whether different laboratories are interpreting the same variant in different ways.

“There is a growing recognition that a clinical lab may see a mutation once or never, so it’s better if all those data could be pooled,” explains James Ostell, chief of the information engineering branch at the NCBI and a member of the ClinVar team. Such information could not only help laboratories to improve quality, it could also prompt research on new variants...."

http://bit.ly/XnWZtA

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Structure - Structural Data in Synthetic Biology Approaches for Studying General Design Principles of Cellular Signaling Networks

 

by
Christina Kiel, Luis Serrano

"In recent years, high-throughput discovery of macromolecular protein structures and complexes has played a major role in advancing a more systems-oriented view of protein interaction and signaling networks. The design of biological systems often employs structural information or structure-based protein design to successfully implement synthetic signaling circuits or for rewiring signaling flows. Here, we summarize the latest advances in using structural information for studying protein interaction and signaling networks, and in synthetic biology approaches. We then provide a perspective of how combining structural biology with engineered cell signaling modules—using additional information from quantitative biochemistry and proteomics, gene evolution, and mathematical modeling—can provide insight into signaling modules and the general design principles of cell signaling. Ultimately, this will improve our understanding of cell- and tissue-type-specific signal transduction. Integrating the quantitative effects of disease mutations into these systems may provide a basis for elucidating the molecular mechanisms of diseases."

http://bit.ly/QrM3t3

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Synthetic Biofilter Wins Through to the Top 'Sweet 16' in Boston | News | Product Design & Development

Synthetic Biofilter Wins Through to the Top 'Sweet 16' in Boston | News | Product Design & Development | SynBioFromLeukipposInstitute | Scoop.it
Months of painstaking work in the laboratory at Bielefeld University‘s Center for Biotechnology (CeBiTec) have paid off: the 15 students participating in this year’s ‘international Genetically Engineered Machine competition’ (iGEM) at the...
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*Chemistry with spatial control using particles and streams*

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Kalinin YV, Murali A, Gracias DH.

"Spatial control of chemical reactions, with micro- and nanometer scale resolution, has important consequences for one pot synthesis, engineering complex reactions, developmental biology, cellular biochemistry and emergent behavior. We review synthetic methods to engineer this spatial control using chemical diffusion from spherical particles, shells and polyhedra. We discuss systems that enable both isotropic and anisotropic chemical release from isolated and arrayed particles to create inhomogeneous and spatially patterned chemical fields. In addition to such finite chemical sources, we also discuss spatial control enabled with laminar flow in 2D and 3D microfluidic networks. Throughout the paper, we highlight applications of spatially controlled chemistry in chemical kinetics, reaction-diffusion systems, chemotaxis and morphogenesis."

http://1.usa.gov/THfnZt

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Community links for the GenoCon2 Synthetic Biology Genomic Design Contest | Facebook

Community links for the GenoCon2 Synthetic Biology Genomic Design Contest | Facebook | SynBioFromLeukipposInstitute | Scoop.it

1. The http://GenoCon.org website containing

- GenoCon2 Challenges with backgrounds,measurement concept, basic science, and manuals

- GenoCon2 Timelines Contest Procedure Overview  GenoCon News About Us

  

2. The http://LinkData.org database  Using LinkData.org you can make an account, find useful data for GenoCon2 and upload your own data.

Using the LinkDataApp programing space http://app.linkdata.org/

you can: 

a) Find useful programs to analyze and process GenoCon2 data,

b) Make your own forked program copy to customize and design your own programs from scratch to enter to GenoCon2

c) Enter The GenoCon2 Contest

d) Write your reports explaining how your programs and designs work 

e) Share and Collaborate using your programs with other GenoCon2 community members

 

3.The GenoCon.org facebook page

 http://www.facebook.com/GenoCon.org/

and GenoCon2 facebook group 

http://www.facebook.com/groups/genocon

 

The GenoCon.org facebook page provides news and interesting links and a place to post community information The GenoCon facebook group provides a forum for questions and answers with the organizers and participants in the GenoCon Community

The LinkData App page http://on.fb.me/VehmUw

in the GenoCon.org facebook page provides links to and descriptions of design tools and entries to the GenoCon contest Challenges shared openly with the the GenoCon 2 Community. 

 

4. GenoCon2 on Scoop.it provides additional news and interesting links.

 http://www.scoop.it/t/genocon-2

 

5. @GenoCcon2 on Twitter for the latest headlines and links.

https://twitter.com/GenoCon2


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Team:Slovenia - 2012.igem.org

Team:Slovenia - 2012.igem.org | SynBioFromLeukipposInstitute | Scoop.it

*Bistable toggle switch in mammalian cells*

- great iGem project from Slovenia

"Biological drugs are being used ever more often as advanced drugs for the treatment of numerous diseases, due to their more specific mode of action. In current therapies the biological drugs are usually distributed more or less throughout the whole body, although each function should often be restricted to a specific organ or tissue. This can cause serious side effects, requires larger dosages and consequently raises the price of therapy. Our solution to this problem was to implant cells producing biological drugs inside the very tissue where the drug is required. The drug producing cells are safely sealed inside microcapsules that prevent cells from spreading throughout the body and protect them from destruction by cells of the host immune system. We constructed a device that allows implanted cells to produce different types of drugs while switching between those production states can be controlled from the outside by a physician, depending on the stage of the disease. We designed our device specifically for the therapy of hepatitis C or heart attack. Against hepatitis C the engineered cells produce a protein with antiviral activity, whose biological activity we have tested and confirmed. After the state of the cells is switched, a protein that improves liver regeneration would be produced. For the therapy after a heart attack we designed cells to suppress local inflammation and promote formation of new blood vessels only around the affected tissue. A physician may initiate self-destruction of the therapeutic cells and capsules by an outside stimulus when the therapy is complete or at any other given time. We believe our system to be safe, effective and applicable in the real world for the therapy of different types of diseases."
http://bit.ly/QbjlN5

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£20m boost for university research projects

£20m boost for university research projects | SynBioFromLeukipposInstitute | Scoop.it

A project at the University of Warwick is one of six to have secured a share of £20m to research synthetic biology http://bit.ly/RTdhWj

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Big Data Is Transforming Healthcare

Big Data Is Transforming Healthcare | SynBioFromLeukipposInstitute | Scoop.it
With the help of personal data trackers, people are measuring just about everything you can think of, Quantified Self founders Kevin Kelly and Gary Wolf said at the inaugural Wired Health Conference in New York.
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SYBHEL Project Final Report and Policy Recommendations

SYBHEL Project Final Report and Policy Recommendations | SynBioFromLeukipposInstitute | Scoop.it

"The SYBHEL Project is now complete. Over the last three years the project partners have investigated the ethical and legal issues of synthetic biology as it pertains to human health and wellbeing. The public section of the SYBHEL Project Final Report and Policy Recommendations can be downloaded here. We would like to thank all of the academics, experts and policy makers who have attended SYBHEL Project events and provided valuable advice and feedback on our work."

http://bit.ly/W1C9LE

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Estimation and Discrimination of Stochastic Biochemical Circuits from Time-Lapse Microscopy Data

Estimation and Discrimination of Stochastic Biochemical Circuits from Time-Lapse Microscopy Data | SynBioFromLeukipposInstitute | Scoop.it

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David Thorsley and Eric Klavins

#The ability of systems and synthetic biologists to observe the dynamics of cellular behavior is hampered by the limitations of the sensors, such as fluorescent proteins, available for use in time-lapse microscopy. In this paper, we propose a generalized solution to the problem of estimating the state of a stochastic chemical reaction network from limited sensor information generated by microscopy. We mathematically derive an observer structure for cells growing under time-lapse microscopy and incorporates the effects of cell division in order to estimate the dynamically-changing state of each cell in the colony. Furthermore, the observer can be used to discrimate between models by treating model indices as states whose values do not change with time. We derive necessary and sufficient conditions that specify when stochastic chemical reaction network models, interpreted as continuous-time Markov chains, can be distinguished from each other under both continual and periodic observation. We validate the performance of the observer on the Thattai-van Oudenaarden model of transcription and translation. The observer structure is most effective when the system model is well-parameterized, suggesting potential applications in synthetic biology where standardized biological parts are available. However, further research is necessary to develop computationally tractable approximations to the exact generalized solution presented here...."

http://bit.ly/S8nqg4

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Largest U.S. Genetic Biobank Reveals Early Findings - ScienceInsider

Largest U.S. Genetic Biobank Reveals Early Findings - ScienceInsider | SynBioFromLeukipposInstitute | Scoop.it

by Jocelyn Kaiser

"Researchers who have assembled a trove of genetic and medical data on 100,000 northern Californians unveiled their initial findings here this week at the annual meeting of the American Society of Human Genetics (ASHG). The effort, which may be the largest such "biobank" in the United States, has already yielded an intriguing connection between mortality and telomeres, the protective DNA sequences that cap chromosome ends, and found new links between genetic variants and disease traits. And that's just the beginning, say the biobank's curators at Kaiser Permanente (KP), the giant health care organization.

The project is one of many that aim to collect medical and DNA data on vast numbers of people and look for links between diseases, lifestyle factors, traits, and genes. More than a decade ago, the company deCODE genetics in Iceland led the way with a biobank now holding data on 140,000 Icelanders; and the UK Biobank, which has enrolled 500,000 people but hasn't yet tested their DNA, may be the largest such study in the world...."

http://bit.ly/ROGiT4

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*Design and testing of a synthetic biology framework for genetic engineering of Corynebacterium glutamicum*

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Ravasi P, Peiru S, Gramajo H, Menzella HG.

"ABSTRACT:
BACKGROUND: Synthetic biology approaches can make a significant contribution to the advance of metabolic engineering by reducing the development time of recombinant organisms. However, most of synthetic biology tools have been developed for Escherichia coli. Here we provide a platform for rapid engineering of C. glutamicum, a microorganism of great industrial interest. This bacteria, used for decades for the fermentative production of amino acids, has recently been developed as a host for the production of several economically important compounds including metabolites and recombinant proteins because of its higher capacity of secretion compared to traditional bacterial hosts like E. coli. Thus, the development of modern molecular platforms may significantly contribute to establish C. glutamicum as a robust and versatile microbial factory.
RESULTS:
A plasmid based platform named pTGR was created where all the genetic components are flanked by unique restriction sites to both facilitate the evaluation of regulatory sequences and the assembly of constructs for the expression of multiple genes. The approach was validated by using reporter genes to test promoters, ribosome binding sites, and for the assembly of dual gene operons and gene clusters containing two transcriptional units. Combinatorial assembly of promoter (tac, cspB and sod) and RBS (lacZ, cspB and sod) elements with different strengths conferred clear differential gene expression of two reporter genes, eGFP and mCherry, thus allowing transcriptional "fine-tuning"of multiple genes. In addition, the platform allowed the rapid assembly of operons and genes clusters for co-expression of heterologous genes, a feature that may assist metabolic pathway engineering.
CONCLUSIONS:
We anticipate that the pTGR platform will contribute to explore the potential of novel parts to regulate gene expression, and to facilitate the assembly of genetic circuits for metabolic engineering of C. glutamicum. The standardization provided by this approach may provide a means to improve the productivity of biosynthetic pathways in microbial factories for the production of novel compounds."

http://1.usa.gov/QtJEy4

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Genetic programs constructed from layered logic gates in single cells

Tae Seok Moon, Chunbo Lou, Alvin Tamsir, Brynne C. Stanton & Christopher A. Voigt

"Genetic programs function to integrate environmental sensors, implement signal processing algorithms and control expression dynamics1. These programs consist of integrated genetic circuits that individually implement operations ranging from digital logic to dynamic circuits2, 3, 4, 5, 6, and they have been used in various cellular engineering applications, including the implementation of process control in metabolic networks and the coordination of spatial differentiation in artificial tissues. A key limitation is that the circuits are based on biochemical interactions occurring in the confined volume of the cell, so the size of programs has been limited to a few circuits1, 7. Here we apply part mining and directed evolution to build a set of transcriptional AND gates in Escherichia coli. Each AND gate integrates two promoter inputs and controls one promoter output. This allows the gates to be layered by having the output promoter of an upstream circuit serve as the input promoter for a downstream circuit. Each gate consists of a transcription factor that requires a second chaperone protein to activate the output promoter. Multiple activator–chaperone pairs are identified from type III secretion pathways in different strains of bacteria. Directed evolution is applied to increase the dynamic range and orthogonality of the circuits. These gates are connected in different permutations to form programs, the largest of which is a 4-input AND gate that consists of 3 circuits that integrate 4 inducible systems, thus requiring 11 regulatory proteins. Measuring the performance of individual gates is sufficient to capture the behaviour of the complete program. Errors in the output due to delays (faults), a common problem for layered circuits, are not observed. This work demonstrates the successful layering of orthogonal logic gates, a design strategy that could enable the construction of large, integrated circuits in single cells."

http://bit.ly/SPMsUw

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Hot Topics: DIYbio- learning to code or learning to type?

Hot Topics: DIYbio- learning to code or learning to type? | SynBioFromLeukipposInstitute | Scoop.it
 
DIYbio: learning to code or learning to type?
at Manchester’s Madlab 
Biological organisms do not follow the neat logic of a software program.
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Synthetic Biology for Dummies, Investors or Both.... - Forbes

Synthetic Biology for Dummies, Investors or Both.... - Forbes | SynBioFromLeukipposInstitute | Scoop.it
In response to the recent publication of “Hacking the President’s DNA,” I’ve been fielding a lot of general questions about synthetic biology. I thought I’d put together a little primer for my readers.
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