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IRSS: a web-based tool for automatic layout and analysis of IRES secondary structure prediction and searching system in silico.

Wu TY, Hsieh CC, Hong JJ, Chen CY, Tsai YS - BMC Bioinformatics (2009)

Bottom Line: We designed an IRES search system, named IRSS, to obtain better results for IRES prediction.Two software programs formed the backbone of IRSS: the RNAL fold program, used to predict local RNA secondary structures by minimum free energy method; and the RNA Align program, used to compare predicted structures.After complete viral genome database search, the IRSS have low error rate and up to 72.3% sensitivity in appropriated parameters.

View Article: PubMed Central - HTML - PubMed

Affiliation: Department of Bioscience Technology, Chung Yuan Christian University, Chung-Li, Taiwan. tywu@cycu.edu.tw

ABSTRACT

Background: Internal ribosomal entry sites (IRESs) provide alternative, cap-independent translation initiation sites in eukaryotic cells. IRES elements are important factors in viral genomes and are also useful tools for bi-cistronic expression vectors. Most existing RNA structure prediction programs are unable to deal with IRES elements.

Results: We designed an IRES search system, named IRSS, to obtain better results for IRES prediction. RNA secondary structure prediction and comparison software programs were implemented to construct our two-stage strategy for the IRSS. Two software programs formed the backbone of IRSS: the RNAL fold program, used to predict local RNA secondary structures by minimum free energy method; and the RNA Align program, used to compare predicted structures. After complete viral genome database search, the IRSS have low error rate and up to 72.3% sensitivity in appropriated parameters.

Conclusion: IRSS is freely available at this website http://140.135.61.9/ires/. In addition, all source codes, precompiled binaries, examples and documentations are downloadable for local execution. This new search approach for IRES elements will provide a useful research tool on IRES related studies.

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The IRSS searching results from entire UTRdb in different length parameters. There are three length parameters applied in this study, L = 100 (A and D), 250 (B and E) and 400 (C and F). To decide the best R value, linear discriminant analysis was applied in each window shown as d, e and f. The best R values are 1.54, 159 and 1.55 for L = 100, 250 and 400 respectively after calculation. Curves of positive and negative IRES elements represent the R value distribution. The original alignment score of every alignment window for all UTRdb data shown as (A), (B) and (C).
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Figure 3: The IRSS searching results from entire UTRdb in different length parameters. There are three length parameters applied in this study, L = 100 (A and D), 250 (B and E) and 400 (C and F). To decide the best R value, linear discriminant analysis was applied in each window shown as d, e and f. The best R values are 1.54, 159 and 1.55 for L = 100, 250 and 400 respectively after calculation. Curves of positive and negative IRES elements represent the R value distribution. The original alignment score of every alignment window for all UTRdb data shown as (A), (B) and (C).

Mentions: The second stage has two purposes. First, the IRSS search capability is evaluated while virus genomes sequences were substituted for the entire UTRdb. The known IRES element which was used for RNA comparison was selected such as HCV IRES domain III structure for example. Second, because of the diversity of known IRES length, the different length parameter (L) of RNALfold should be tested. Three L parameters, 100, 250 and 400, were applied to inspect the discrimination for IRES elements from UTRdb. To determine the best cut-off values of R value in different L parameters, the HCV and Pestivirus 5' UTR are designed as the positive group and others are the negative group. Those records were calculated their R value and estimated their distribution by linear discriminant analysis (see Figure 3D, E, F and additional file 1). The normalized R value indicates that two separate groups were made when the cut-off value was determined.


IRSS: a web-based tool for automatic layout and analysis of IRES secondary structure prediction and searching system in silico.

Wu TY, Hsieh CC, Hong JJ, Chen CY, Tsai YS - BMC Bioinformatics (2009)

The IRSS searching results from entire UTRdb in different length parameters. There are three length parameters applied in this study, L = 100 (A and D), 250 (B and E) and 400 (C and F). To decide the best R value, linear discriminant analysis was applied in each window shown as d, e and f. The best R values are 1.54, 159 and 1.55 for L = 100, 250 and 400 respectively after calculation. Curves of positive and negative IRES elements represent the R value distribution. The original alignment score of every alignment window for all UTRdb data shown as (A), (B) and (C).
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC2698906&req=5

Figure 3: The IRSS searching results from entire UTRdb in different length parameters. There are three length parameters applied in this study, L = 100 (A and D), 250 (B and E) and 400 (C and F). To decide the best R value, linear discriminant analysis was applied in each window shown as d, e and f. The best R values are 1.54, 159 and 1.55 for L = 100, 250 and 400 respectively after calculation. Curves of positive and negative IRES elements represent the R value distribution. The original alignment score of every alignment window for all UTRdb data shown as (A), (B) and (C).
Mentions: The second stage has two purposes. First, the IRSS search capability is evaluated while virus genomes sequences were substituted for the entire UTRdb. The known IRES element which was used for RNA comparison was selected such as HCV IRES domain III structure for example. Second, because of the diversity of known IRES length, the different length parameter (L) of RNALfold should be tested. Three L parameters, 100, 250 and 400, were applied to inspect the discrimination for IRES elements from UTRdb. To determine the best cut-off values of R value in different L parameters, the HCV and Pestivirus 5' UTR are designed as the positive group and others are the negative group. Those records were calculated their R value and estimated their distribution by linear discriminant analysis (see Figure 3D, E, F and additional file 1). The normalized R value indicates that two separate groups were made when the cut-off value was determined.

Bottom Line: We designed an IRES search system, named IRSS, to obtain better results for IRES prediction.Two software programs formed the backbone of IRSS: the RNAL fold program, used to predict local RNA secondary structures by minimum free energy method; and the RNA Align program, used to compare predicted structures.After complete viral genome database search, the IRSS have low error rate and up to 72.3% sensitivity in appropriated parameters.

View Article: PubMed Central - HTML - PubMed

Affiliation: Department of Bioscience Technology, Chung Yuan Christian University, Chung-Li, Taiwan. tywu@cycu.edu.tw

ABSTRACT

Background: Internal ribosomal entry sites (IRESs) provide alternative, cap-independent translation initiation sites in eukaryotic cells. IRES elements are important factors in viral genomes and are also useful tools for bi-cistronic expression vectors. Most existing RNA structure prediction programs are unable to deal with IRES elements.

Results: We designed an IRES search system, named IRSS, to obtain better results for IRES prediction. RNA secondary structure prediction and comparison software programs were implemented to construct our two-stage strategy for the IRSS. Two software programs formed the backbone of IRSS: the RNAL fold program, used to predict local RNA secondary structures by minimum free energy method; and the RNA Align program, used to compare predicted structures. After complete viral genome database search, the IRSS have low error rate and up to 72.3% sensitivity in appropriated parameters.

Conclusion: IRSS is freely available at this website http://140.135.61.9/ires/. In addition, all source codes, precompiled binaries, examples and documentations are downloadable for local execution. This new search approach for IRES elements will provide a useful research tool on IRES related studies.

Show MeSH