i-Score Designer

Background

The i-Score Designer calculates nine different siRNA designing scores of Ui-Tei [1]‚ Amarzguioui [2]‚ Hsieh [3]‚ Takasaki [4]‚ s-Biopredsi [5]‚ i-Score [6]‚ Reynolds [7]‚ Katoh [8]‚ and DSIR [9]. The nine scores calculated by this service are identical to those published by individual authors except for s-Biopredsi: The correlation coefficient of s-Biopredsi and Biopredsi is 0.998. Among the nine different scores‚ three scores of i-Score [6]‚ s-Biopredsi [5]‚ and DSIR [9] are classified as the second generation algorithms that are more dependable than the others. s-Biopredsi and DSIR are based on 21-mer siRNA sequences‚ but only a 19-mer segment forming a RNA duplex is shown in the results. Note that there are no s-Biopredsi and DSIR scores at positions 1 and 2‚ where two additional nucleotides do not exist at the 5’end. The iScore Designer also calculates the following parameters:


  1. ΔG value of the most stable secondary structure of an siRNA strand according to the RNA mfold algorithm.
  2. Dinucleotide ΔG values at the 5’ and 3’ ends
  3. The ΔG value throughout the siRNA stretch
  4. The maximum length of GC stretch
  5. %GC content

Instructions

  1. Enter your cDNA sequence either in RNA or DNA. Only A‚ C‚ G‚ T‚ and U nucleotides are accepted.
  2. Alternatively‚ enter individual 19-mer sense siRNA sequences separated by line breaks and click on the checkbox below to calculate prediction scores individually.
    s-Biopredsi and DSIR are not calculated with this functionality.
  3. Press “Analyze” button.
  4. The results show ten best siRNAs according to i-Score‚ s-Biopredsi‚ and DSIR. The best siRNA is likely the one that shows high ranks in all of these scores.
  5. The distributions of these scores are indicated below.
  6. All possible 19-mer siRNA sequences and their respective scores are indicated at the bottom.

Check here for analyzing individual 19-mer sense siRNA sequences separated by line breaks.

A references to be cited for the i-Score designer

Ichihara M‚ Murakumo Y‚ Masuda A‚ Matsuura T‚ Asai N‚ Jijiwa M‚ Ishida M‚ Shinmi J‚ Yatsuya H‚ Qiao S‚ Takahashi M‚ Ohno K. Thermodynamic instability of siRNA duplex is a prerequisite for dependable prediction of siRNA activities. Nucleic Acids Res 35:e123‚ 2007 [PMID: 17884914].

References in the background section

  1. Ui-Tei K‚ Naito Y‚ Takahashi F‚ Haraguchi T‚ Ohki-Hamazaki H‚ Juni A‚ Ueda R‚ Saigo K. Guidelines for the selection of highly effective siRNA sequences for mammalian and chick RNA interference. Nucleic Acids Res 32: 936-948‚ 2004.
  2. Amarzguioui M‚ Prydz H. An algorithm for selection of functional siRNA sequences. Biochem Biophys Res Commun 316: 1050-1058‚ 2004.
  3. Hsieh AC‚ Bo R‚ Manola J‚ Vazquez F‚ Bare O‚ Khvorova A‚ Scaringe S‚ Sellers WR. A library of siRNA duplexes targeting the phosphoinositide 3-kinase pathway: determinants of gene silencing for use in cell-based screens. Nucleic Acids Res 32: 893-901‚ 2004.
  4. Takasaki S‚ Kotani S‚ Konagaya A. An effective method for selecting siRNA target sequences in mammalian cells. Cell Cycle 3: 790-5‚ 2004.
  5. Huesken D‚ Lange J‚ Mickanin C‚ Weiler J‚ Asselbergs F‚ Warner J‚ Meloon B‚ Engel S‚ Rosenberg A‚ Cohen D‚ Labow M‚ Reinhardt M‚ Natt F‚ Hall J. Design of a genome-wide siRNA library using an artificial neural network. Nat Biotechnol 23: 995-1001‚ 2005.
  6. Ichihara M‚ Murakumo Y‚ Masuda A‚ Matsuura T‚ Asai N‚ Jijiwa M‚ Ishida M‚ Shinmi J‚ Yatsuya H‚ Qiao S‚ Takahashi M‚ Ohno K. Thermodynamic instability of siRNA duplex is a prerequisite for dependable prediction of siRNA activities. Nucleic Acids Res 35: e123‚ 2007.
  7. Reynolds A‚ Leake D‚ Boese Q‚ Scaringe S‚ Marshall WS‚ Khvorova A. Rational siRNA design for RNA interference. Nat Biotechnol 22: 326-330‚ 2004.
  8. Katoh T‚ Suzuki T. Specific residues at every third position of siRNA shape its efficient RNAi activity. Nucleic Acids Res 35: e27‚ 2007.
  9. Vert JP‚ Foveau N‚ Lajaunie C‚ Vandenbrouck Y. An accurate and interpretable model for siRNA efficacy prediction. BMC Bioinformatics 7: 520‚ 2006.

Acknowledgements

The siRNA Designer web service is made available by KAKENHI (Grant-in-Aid for Scientific Research) on Priority Areas "Systems Genomics" from the Ministry of Education‚ Culture‚ Sports‚ Science and Technology of Japan.

Revision history

Feb 26 2009       Ver.1.0          Initiation of the iScore web-service program
Feb 28 2012       Ver.1.1          A bug that did not recognize line breaks at every 19 mer is fixed.