The algorithms and scoring models used in this saRNA Designer tool are based on the following peer-reviewed scientific literature:
1. Algorithm & Scoring Logic
These articles are the basis of the "Scoring System" (Reynolds Score) and positional preferences (10th base A, etc.) in the code.
Reynolds, A., et al. (2004). Rational siRNA design for RNA interference. Nature Biotechnology, 22(3), 326–330.
Implementation: Basis for the position-specific scoring matrix (PSSM) and GC content filtering.
Ui-Tei, K., et al. (2004). Guidelines for the selection of highly effective siRNA sequences for mammalian and chick RNA interference. Nucleic Acids Research, 32(3), 936-948.
Implementation: Used for defining the thermodynamic asymmetry rules (A/U richness at the 5' end of the antisense strand).
2. Thermodynamics & Energy Calculation
The nnParams variable and Gibbs Energy ($\Delta G$) calculation in the code were made with the data from these sources.
Mathews, D. H., Disney, M. D., Childs, J. L., Schroeder, S. J., Zuker, M., & Turner, D. H. (2004). Incorporating chemical modification constraints into a dynamic programming algorithm for prediction of RNA secondary structure. Proceedings of the National Academy of Sciences, 101(19), 7287-7292.
Implementation: Source of the "Nearest-Neighbor" thermodynamic parameters for RNA-RNA duplex stability.
Freier, S. M., et al. (1986). Improved free-energy parameters for predictions of RNA duplex stability. Proceedings of the National Academy of Sciences, 83(24), 9373-9377.
Implementation: Foundational thermodynamic values for loop and stack calculations.
3. Biological Mechanism (Biological Basis: saRNA)
Li, L. C., et al. (2006). Small dsRNAs induce transcriptional activation in human cells. Proceedings of the National Academy of Sciences, 103(46), 17337-17342.
Context: Discovery of the RNA activation (RNAa) mechanism targeting gene promoters.
Portnoy, V., et al. (2011). Small RNA and transcriptional upregulation. Wiley Interdisciplinary Reviews: RNA, 2(5), 748-760.
Context: Guidelines for targeting promoter sequences.