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An efficient simulator of 454 data using configurable statistical models
Linköping University, Department of Physics, Chemistry and Biology, Bioinformatics. Linköping University, The Institute of Technology.
Karolinska Institutet. (Department of Cell and Molecular Biology, Science for Life Laboratory)
Linköping University, Department of Physics, Chemistry and Biology, Bioinformatics. Linköping University, The Institute of Technology.
2011 (English)In: BMC Research Notes, ISSN 1756-0500, Vol. 4, no 449Article in journal (Refereed) Published
Abstract [en]


Roche 454 is one of the major 2nd generation sequencing platforms. The particular characteristics of 454 sequence data   pose new challenges for bioinformatic analyses, e.g. assembly and alignment search   algorithms. Simulation of these data is therefore useful, in order to further assess   how bioinformatic applications and algorithms handle 454 data.


We developed a new application named 454sim for simulation of 454 data at high speed   and accuracy. The program is multi-thread capable and is available as C++ source code   or pre-compiled binaries. Sequence reads are simulated by 454sim using a set of statistical   models for each chemistry. 454sim simulates recorded peak intensities, peak quality   deterioration and it calculates quality values. All three generations of the Roche   454 chemistry ('GS20', 'GS FLX' and 'Titanium') are supported and defined in external   text files for easy access and tweaking.


We present a new platform independent application named 454sim. 454sim is generally   200 times faster compared to previous programs and it allows for simple adjustments   of the statistical models. These improvements make it possible to carry out more complex   and rigorous algorithm evaluations in a reasonable time scale.

Place, publisher, year, edition, pages
2011. Vol. 4, no 449
National Category
Medical and Health Sciences
URN: urn:nbn:se:liu:diva-79435DOI: 10.1186/1756-0500-4-449OAI: diva2:541808
Available from: 2012-07-24 Created: 2012-07-24 Last updated: 2014-09-25
In thesis
1. Bioinformatic methods for characterization of viral pathogens in metagenomic samples
Open this publication in new window or tab >>Bioinformatic methods for characterization of viral pathogens in metagenomic samples
2013 (English)Doctoral thesis, comprehensive summary (Other academic)
Abstract [en]

Virus infections impose a huge disease burden on humanity and new viruses are continuously found. As most studies of viral disease are limited to theinvestigation of known viruses, it is important to characterize all circulating viruses. Thus, a broad and unselective exploration of the virus flora would be the most productive development of modern virology. Fueled by the reduction in sequencing costs and the unbiased nature of shotgun sequencing, viral metagenomics has rapidly become the strategy of choice for this exploration.

This thesis mainly focuses on improving key methods used in viral metagenomics as well as the complete viral characterization of two sets of samples using these methods. The major methods developed are an efficient automated analysis pipeline for metagenomics data and two novel, more accurate, alignment algorithms for 454 sequencing data. The automated pipeline facilitates rapid, complete and effortless analysis of metagenomics samples, which in turn enables detection of potential pathogens, for instance in patient samples. The two new alignment algorithms developed cover comparisons both against nucleotide and  protein databases, while retaining the underlying 454 data representation. Furthermore, a simulator for 454 data was developed in order to evaluate these methods. This simulator is currently the fastest and most complete simulator of 454 data, which enables further development of algorithms and methods. Finally, we have successfully used these methods to fully characterize a multitude of samples, including samples collected from children suffering from severe lower respiratory tract infections as well as patients diagnosed with chronic fatigue syndrome, both of which presented in this thesis. In these studies, a complete viral characterization has revealed the presence of both expected and unexpected viral pathogens as well as many potential novel viruses.

Place, publisher, year, edition, pages
Linköping: Linköping University Electronic Press, 2013. 65 p.
Linköping Studies in Science and Technology. Dissertations, ISSN 0345-7524 ; 1489
National Category
Natural Sciences
urn:nbn:se:liu:diva-86194 (URN)978-91-7519-745-6 (ISBN)
Public defence
2013-01-25, Planck, Fysikhuset, Campus Valla, Linköpings universitet, Linköping, 10:15 (English)
Available from: 2012-12-10 Created: 2012-12-10 Last updated: 2012-12-10Bibliographically approved

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