Standard DNA sequencing and analysis of a pathogen genome is time-intensive and likely impractical during an emergency. Researchers have now developed a comparative genomics strategy to drastically reduce the time needed to accurately identify unique genetic properties of a potential outbreak strain. This report, which demonstrates the approach using next-generation sequencing technology, is published online today in Genome Research.
Sanger DNA sequencing, the established technology used to sequence the genomes of many species, including the genomes of humans and hundreds of bacteria, could potentially be used to sequence and analyze a new human pathogen. However, the time required for sequencing and subsequent analysis, or “finishing,” is such that this approach is not feasible when a rapid response to an outbreak or bioterrorist attack is required. New sequencing technologies are now available, allowing an entire bacterial genome to be sequenced in several hours, but time-intensive finishing steps are still required to determine the complete genome sequence.
In this study, researchers led by Drs. Bernard La Scola and Didier Raoult of the University of the Mediterranean set out to determine whether a rapidly sequenced incomplete genome could be used to quickly characterize an outbreak strain by comparative analysis. “In the context of an outbreak, a quick approach may help to identify immediately the genetic determinants responsible for modified virulence or transmission, explains La Scola. “The aim of this work was to evaluate the recently available automated pyrosequencing technology without finishing for this purpose.”
F. tularensis, the causative pathogen of tularemia, is one of the most infectious bacteria known, and there is particular concern that this organism could be manipulated for use as a biological weapon. La Scola and colleagues sequenced a strain isolated from a tularemia patient using the Roche/454 Life Sciences GS20 sequencing system, and compared these sequences with several other strains of F. tularensis, including a strain with reduced pathogencity and an antiobiotic-resistant strain.
The researchers demonstrated that next-generation sequencing of a bacterial genome without finishing could be used to effectively identify several unique features of the F. tularensis clinical strain in a matter of weeks. “By using this strategy, if there are a sufficient number of bioinformaticians working on the project, DNA extraction to complete analysis of the genome can take approximately 6 weeks,” describes La Scola. “We demonstrated that this strategy was efficient to detect gene polymorphisms such as a gene modification responsible for antibiotic resistance, and loss of genetic material.” Furthermore, La Scola and colleagues were able to distinguish the clinical strain from 80 other strains of F. tularensis.
While high-throughput sequencing technology and the comparative genomic analysis strategy outlined in this work have significantly decreased the time required for characterization of an outbreak strain, La Scola notes that future advances in software for sequence data analysis and genome comparison could speed up the process even further.
Scientists from the University of the Mediterranean (Marseilles, France) contributed to this study.
This work was supported by Sanofi-Aventis France, Bayer Pharma, and the European Commission.
Bernard La Scola, M.D., Ph.D. (email@example.com; +33-4-91385517) and Didier Raoult, M.D., Ph.D. (firstname.lastname@example.org, +33-4-91385517) have agreed to be contacted for more information.
Interested reporters may obtain copies of the manuscript from Peggy Calicchia, Editorial Secretary, Genome Research (email@example.com; +1-516-422-4012).
About the article:
The manuscript will be published online ahead of print on April 11, 2008. Its full citation is as follows: La Scola, B., Elkarkouri, K., Li, W., Wahab, T., Fournous, G., Rolain, J., Biswas, S., Drancourt, M., Robert, C., Audic, S., Löfdahl, S., and Raoult, D. Rapid comparative genomic analysis for clinical microbiology: The Francisella tularensis paradigm. Genome Res. doi:10.1101/gr.7126608.
About Genome Research:
Genome Research (www.genome.org) is an international, continuously published, peer-reviewed journal published by Cold Spring Harbor Laboratory Press. Launched in 1995, it is one of the five most highly cited primary research journals in genetics and genomics.
About Cold Spring Harbor Laboratory Press:
Cold Spring Harbor Laboratory Press is an internationally renowned publisher of books, journals, and electronic media, located on Long Island, New York. It is a division of Cold Spring Harbor Laboratory, an innovator in life science research and the education of scientists, students, and the public. For more information, visit www.cshlpress.com.
Genome Research issues press releases to highlight significant research studies that are published in the journal.
Solving the efficiency of Gram-negative bacteria
22.03.2019 | Harvard University
Bacteria bide their time when antibiotics attack
22.03.2019 | Rice University
DESY and MPSD scientists create high-order harmonics from solids with controlled polarization states, taking advantage of both crystal symmetry and attosecond electronic dynamics. The newly demonstrated technique might find intriguing applications in petahertz electronics and for spectroscopic studies of novel quantum materials.
The nonlinear process of high-order harmonic generation (HHG) in gases is one of the cornerstones of attosecond science (an attosecond is a billionth of a...
Nano- and microtechnology are promising candidates not only for medical applications such as drug delivery but also for the creation of little robots or flexible integrated sensors. Scientists from the Max Planck Institute for Polymer Research (MPI-P) have created magnetic microparticles, with a newly developed method, that could pave the way for building micro-motors or guiding drugs in the human body to a target, like a tumor. The preparation of such structures as well as their remote-control can be regulated using magnetic fields and therefore can find application in an array of domains.
The magnetic properties of a material control how this material responds to the presence of a magnetic field. Iron oxide is the main component of rust but also...
Due to the special arrangement of its molecules, a new coating made of corn starch is able to repair small scratches by itself through heat: The cross-linking via ring-shaped molecules makes the material mobile, so that it compensates for the scratches and these disappear again.
Superficial micro-scratches on the car body or on other high-gloss surfaces are harmless, but annoying. Especially in the luxury segment such surfaces are...
The Potsdam Echelle Polarimetric and Spectroscopic Instrument (PEPSI) at the Large Binocular Telescope (LBT) in Arizona released its first image of the surface magnetic field of another star. In a paper in the European journal Astronomy & Astrophysics, the PEPSI team presents a Zeeman- Doppler-Image of the surface of the magnetically active star II Pegasi.
A special technique allows astronomers to resolve the surfaces of faraway stars. Those are otherwise only seen as point sources, even in the largest telescopes...
Researchers at Chalmers University of Technology and the University of Gothenburg, Sweden, have proposed a way to create a completely new source of radiation. Ultra-intense light pulses consist of the motion of a single wave and can be described as a tsunami of light. The strong wave can be used to study interactions between matter and light in a unique way. Their research is now published in the scientific journal Physical Review Letters.
"This source of radiation lets us look at reality through a new angle - it is like twisting a mirror and discovering something completely different," says...
11.03.2019 | Event News
01.03.2019 | Event News
28.02.2019 | Event News
22.03.2019 | Life Sciences
22.03.2019 | Life Sciences
22.03.2019 | Information Technology