Team:VT-ENSIMAG Biosecurity

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=Introduction: presentation of our project=
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As part of our iGEM 2010 project, we are implementing the draft Government guidance for sequence screening, characterizing its performance, and suggesting improvements. Our findings will not only quantify an interpretation of the Government guidance, but should also help to provide future developers of screening software with the data necessary to develop more robust sequence screening tools. Our work has direct implications for both iGEM and the field of synthetic biology.  
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The Web
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value="https://2010.igem.org/Team:VT-ENSIMAG_Biosecurity" checked /> In WIKI <br />
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Gene synthesis technology gives scientists an unparalleled capability to manipulate genomes. Over the past several decades, an entire commercial industry has developed to inexpensively produce genes on a large scale. It is this industry which provides the manufactured genes and standardized parts to make synthetic biology, and iGEM, possible.
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Synthetic genomics, like synthetic biology, has the potential to act as both a great benefit and a great detriment to public health and national security. A precedence for the dual use of synthetic genomics is the reconstruction of the virus responsible for the pandemic 1918 Spanish Flu in 2005 by researchers at the CDC ([[Team:VT-ENSIMAG/influenza_virus|See more]]). This highly infectious strain is estimated to have killed as many as 50,000,000 people worldwide. Although the 1918 Spanish flu genes were synthesized for legitimate research purposes,  they could have just as easily been used to reconstruct a biological weapon. It should be noted that the reconstructed strain was partially attenuated. This, however, does not preclude the possibility of more virulent forms being engineered in the future. Although such engineering is difficult at the moment, advances in this technology over the next decade could make it easier for bioterrorists to harm the Public. According to a 2004 report by the U.S. National Intelligence Council, its greatest security concern over the coming years is that terrorists will acquire biological agents for use as weapons of mass destruction (NIC, 2004).
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Many nucleotide sequences encoding for or derived from dangerous toxins or pathogens can be freely accessed on the U.S. National Center for Biotechnology Information GenBank (NCBI-GenBank). The ease with which dangerous sequences can be located and synthesized presents novel threats to both public health and national security. To prevent illicit activities by end users of de novo synthesized genes, it is crucial to stop their manufacture at the source: gene synthesis companies. Therefore, effective and efficient screening measures must be developed to identify sequences of concern within a synthesis order.
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<table width="133" border="0" cellspacing="0" cellpadding="3"><tr><td align="center"><a href="http://www.website-hit-counters.com/" target="_blank"><img src="http://www.website-hit-counters.com/cgi-bin/image.pl?URL=427634-6314" alt="" title="HITS" border="0" ></a></td></tr><tr><td align="center"><font style="font-family: Geneva, Arial, Helvetica, sans-serif; font-size: 9px; color: #330006; text-decoration: none;"> <a href="http://www.website-hit-counters.com/" target="_blank" style="font-family: Geneva, Arial, Helvetica, sans-serif; font-size: 10px; color: #330006; text-decoration: none;" title="Hits for WIKI">Hits for WIKI</a> </font></td></tr></table>
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The United States government recognizes its responsibility to protect the public and in November, 2009, published a draft guidance for sequence screening. As part of our iGEM 2010 project, we are implementing the draft Government guidance for sequence screening, characterizing its performance, and suggesting improvements.  
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=Abstract=
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[[Image:Dna-computer.jpg|180px|right]]
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In order to mitigate the biosecurity risks associated with the potential dual use of gene synthesis, the U.S. Government published a draft version of a “Screening Framework Guidance for Synthetic Double-Stranded DNA Providers" in late 2009. This document outlines a minimal DNA sequence screening protocol that gene synthesis companies are encouraged to use prior to fulfilling an order. The protocol relies on the “Best Match” method developed in response to the limitations of other screening protocols previously proposed by trade organizations. The objective of the “Best Match” method is to identify sequences which are uniquely related to Select Agents or Toxins. The GenoTHREAT software is being developed in accordance with the Government guidance and, to our knowledge, is the first implementation of the sequence screening procedure outlined in the guidance. Although software characterization has elucidated both strengths and limitations, GenoTHREAT appears to be a viable tool for sequence screening
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The iGEM competition has developed a tool-box of standardized parts for use by synthetic biologists. Without screening software, dangerous sequences could find their way into this tool-box. If such sequences were used to engineer organisms with novel capabilities, the repercussions could be significant. As part of our project, we have screened the iGEM standard registry of parts. GenoTHREAT did not identify any potentially dangerous sequences currently unknown to iGEM officials. However, this does not preclude the potential addition of dangerous sequences to a synthetic biology registry. The emphasis placed on safety and security by both iGEM and the synthetic biology community only reinforces the clear need for more cost effective and accurate screening methods. The deeper understanding of screening technology provided by our results could therefore play an integral role in both the future of the competition and the field.
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=Accomplishments=
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National Science Foundation grant awarded for development of GenoTHREAT software [[Image:VT-ENS_SAT_collage.jpg|180px|left]]
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http://www.nsf.gov/awardsearch/showAward.do?AwardNumber=1060776
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The VT-ENSIMAG Biosecurity team has been invited to present their findings to officials at the Federal Bureau of Investigations (FBI) after the iGEM Jamboree.
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Several online news articles describing the VT-ENSIMAG project have been published. See [[Team:VT-ENSIMAG/Media_Links|Media Links]] section for more information.
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=Additional work=
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In addition to successfully developing a sequence screening software, we have also screened the iGEM registry with this software ([[Team:VT-ENSIMAG/Registry|registry screening]]).
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We have also developed an application to design USER Fussion primer sequences from PCR experiments. Given the error-prone and tedious nature of designing primers by hand, this software will improve the accuracy of primer designs in the future as well as save teams much time.  ([[Team:VT-ENSIMAG/User_primer|User primer]]).
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This application is available to download and open-source ([[Team:VT-ENSIMAG/User_primer#Download_the_User_Primer_Calculator|download it]]).
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=Conclusions=
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A prototype sequence screening software, GenoTHREAT, was developed by our team in accordance with a draft sequence screening guidance published by the United States Government in 2009. To the best of our knowledge, this implementation of the draft guidance is the first of its kind. Preliminary testing of the software was completed and elucidated several operational characteristics. For instance, the keyword and anti-keyword lists used to identify "Best Matches" as Select Agents or Toxins play a critical role in the efficacy of the software. The quality of the sequence screening is further influenced by the BLAST parameters used and the system on which the software is run. Although the average number of sequences currently screened by companies across the industry is unknown, readily available hardware systems such as Sirion would allow a company to screen several hundred sequences of under 10,000bps per day. For more information concerning the computer systems used in testing, see section [[Team:VT_Ensimag_2010-Biosecurity/Implementations| Different implementations]].
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Any sequence screening software must be able to recognize sequences which have been modified but which can be reconstituted into a functional form. The GenoTHREAT software was able to effectively identify sequences containing "hidden" lengths of Select Agent or Toxins, sequences which have been randomly mutated, or codon optimized sequences. A manuscript is being prepared for publication which will explain the methods and results in greater detail.
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To test the software in a real world environment, the iGEM sequence registry was screened using GenoTHREAT. Upon a manual review of the hits, one dangerous sequence were identified: a gene for Botulinum Neurotoxin A. This sequence was already known by iGEM officials to be part of the registry.
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Preliminary testing of the prototype sequence screening software, GenoTHREAT, has identified it as a potentially viable software for implementation in a large scale screening environment such as the iGEM registry or gene synthesis industry .
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iGEM attempts to develop a tool-box of standardized parts for use by synthetic biologists. Without screening software, dangerous sequences could find their way into this tool-box. If such sequences were used to engineer organisms with novel capabilities, the repercussions could be significant. The deeper understanding of screening technology provided by our results could therefore play an integral role in both the future of the competition and the field.
 
=Who are we?=
=Who are we?=
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We are a software team, composed by 5 students (2 from ENSIMAG and 3 from Virginia Tech) working in the Virginia Bioinformatics Institut, under the supervision of Jean Peccoud and with Laura Adam as advisor.  
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[[Image:VT-ENSIMAG_Biosecurity_logo.png|200px|right]] We are a software team, composed by 5 students (2 from ENSIMAG and 3 from Virginia Tech) working at the Virginia Bioinformatics Institute. Our advisors were Dr. Jean Peccoud and Laura Adam.  
The team is more thoroughly presented in [[Team:VT-ENSIMAG/Our_Team|Our team]].
The team is more thoroughly presented in [[Team:VT-ENSIMAG/Our_Team|Our team]].
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=project overview=
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Our team was also presented in some scientific articles, which are available in [[Team:VT-ENSIMAG/Media_Links|Media]].
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<p style="font-size:20px;font-family:times">We would like to thanks our sponsors:</p>
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You <strong>MUST</strong> have a team description page, a project abstract, a complete project description, a lab notebook, and a safety page.  PLEASE keep all of your pages within your teams namespace.
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<h1>SAIC</h1>
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[[Image:SAIC.jpeg|100px|left]]
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Visit the <a href="http://www.saic.com//">SAIC</a> website.
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<br>
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<h1>MITRE</h1>
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[[Image:mitre.jpeg|100px|left]]
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Visit the <a href="http://www.mitre.org///">MITRE</a> website.
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Latest revision as of 03:29, 28 October 2010


VT-ENSIMAG over VT campus long.png

Home




DNAside.png

Home

Our team

Sequence screening

The software: GenoTHREAT

Tests and Results

Screening of the iGEM registry

PCR fusion primer

Lab notebook

Safety

Media Links

Comments

SAIC.jpeg

Mitre.jpeg





The Web In WIKI

Abstract

Dna-computer.jpg

In order to mitigate the biosecurity risks associated with the potential dual use of gene synthesis, the U.S. Government published a draft version of a “Screening Framework Guidance for Synthetic Double-Stranded DNA Providers" in late 2009. This document outlines a minimal DNA sequence screening protocol that gene synthesis companies are encouraged to use prior to fulfilling an order. The protocol relies on the “Best Match” method developed in response to the limitations of other screening protocols previously proposed by trade organizations. The objective of the “Best Match” method is to identify sequences which are uniquely related to Select Agents or Toxins. The GenoTHREAT software is being developed in accordance with the Government guidance and, to our knowledge, is the first implementation of the sequence screening procedure outlined in the guidance. Although software characterization has elucidated both strengths and limitations, GenoTHREAT appears to be a viable tool for sequence screening.

The iGEM competition has developed a tool-box of standardized parts for use by synthetic biologists. Without screening software, dangerous sequences could find their way into this tool-box. If such sequences were used to engineer organisms with novel capabilities, the repercussions could be significant. As part of our project, we have screened the iGEM standard registry of parts. GenoTHREAT did not identify any potentially dangerous sequences currently unknown to iGEM officials. However, this does not preclude the potential addition of dangerous sequences to a synthetic biology registry. The emphasis placed on safety and security by both iGEM and the synthetic biology community only reinforces the clear need for more cost effective and accurate screening methods. The deeper understanding of screening technology provided by our results could therefore play an integral role in both the future of the competition and the field.



Accomplishments

National Science Foundation grant awarded for development of GenoTHREAT software
VT-ENS SAT collage.jpg

http://www.nsf.gov/awardsearch/showAward.do?AwardNumber=1060776

The VT-ENSIMAG Biosecurity team has been invited to present their findings to officials at the Federal Bureau of Investigations (FBI) after the iGEM Jamboree.

Several online news articles describing the VT-ENSIMAG project have been published. See Media Links section for more information.

Additional work

In addition to successfully developing a sequence screening software, we have also screened the iGEM registry with this software (registry screening).

We have also developed an application to design USER Fussion primer sequences from PCR experiments. Given the error-prone and tedious nature of designing primers by hand, this software will improve the accuracy of primer designs in the future as well as save teams much time. (User primer). This application is available to download and open-source (download it).

Conclusions

A prototype sequence screening software, GenoTHREAT, was developed by our team in accordance with a draft sequence screening guidance published by the United States Government in 2009. To the best of our knowledge, this implementation of the draft guidance is the first of its kind. Preliminary testing of the software was completed and elucidated several operational characteristics. For instance, the keyword and anti-keyword lists used to identify "Best Matches" as Select Agents or Toxins play a critical role in the efficacy of the software. The quality of the sequence screening is further influenced by the BLAST parameters used and the system on which the software is run. Although the average number of sequences currently screened by companies across the industry is unknown, readily available hardware systems such as Sirion would allow a company to screen several hundred sequences of under 10,000bps per day. For more information concerning the computer systems used in testing, see section Different implementations. Any sequence screening software must be able to recognize sequences which have been modified but which can be reconstituted into a functional form. The GenoTHREAT software was able to effectively identify sequences containing "hidden" lengths of Select Agent or Toxins, sequences which have been randomly mutated, or codon optimized sequences. A manuscript is being prepared for publication which will explain the methods and results in greater detail. To test the software in a real world environment, the iGEM sequence registry was screened using GenoTHREAT. Upon a manual review of the hits, one dangerous sequence were identified: a gene for Botulinum Neurotoxin A. This sequence was already known by iGEM officials to be part of the registry.

Preliminary testing of the prototype sequence screening software, GenoTHREAT, has identified it as a potentially viable software for implementation in a large scale screening environment such as the iGEM registry or gene synthesis industry .


Who are we?

VT-ENSIMAG Biosecurity logo.png
We are a software team, composed by 5 students (2 from ENSIMAG and 3 from Virginia Tech) working at the Virginia Bioinformatics Institute. Our advisors were Dr. Jean Peccoud and Laura Adam.

The team is more thoroughly presented in Our team.

Our team was also presented in some scientific articles, which are available in Media.



We would like to thanks our sponsors:

SAIC

SAIC.jpeg

Visit the SAIC website.



MITRE

Mitre.jpeg

Visit the MITRE website.

ALIEN DNA.png
VT-ENSIMAG logo.png
ALIEN DNA.png