Design of a genome-wide siRNA library using an artificial neural network

@article{Huesken2005DesignOA,
  title={Design of a genome-wide siRNA library using an artificial neural network},
  author={Dieter Huesken and Joerg Lange and Craig Mickanin and Jan Weiler and Fred A. M. Asselbergs and Justin Warner and Brian Meloon and Sharon Engel and Avi Rosenberg and Dalia Cohen and Mark A. Labow and Mischa Reinhardt and Francois Natt and Jonathan Hall},
  journal={Nature Biotechnology},
  year={2005},
  volume={23},
  pages={995-1001}
}
The largest gene knock-down experiments performed to date have used multiple short interfering/short hairpin (si/sh)RNAs per gene. To overcome this burden for design of a genome-wide siRNA library, we used the Stuttgart Neural Net Simulator to train algorithms on a data set of 2,182 randomly selected siRNAs targeted to 34 mRNA species, assayed through a high-throughput fluorescent reporter gene system. The algorithm, (BIOPREDsi), reliably predicted activity of 249 siRNAs of an independent test… Expand
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References

SHOWING 1-10 OF 35 REFERENCES
A resource for large-scale RNA-interference-based screens in mammals
TLDR
The construction and application of a shRNA expression library targeting 9,610 human and 5,563 mouse genes is reported, which suggests that the large-scale RNAi library can be used in specific, genetic applications in mammals, and will become a valuable resource for gene analysis and discovery. Expand
A library of siRNA duplexes targeting the phosphoinositide 3-kinase pathway: determinants of gene silencing for use in cell-based screens.
TLDR
Analysis of the parameters correlating with effective knockdown showed that among duplexes that achieved a >70% knockdown of the mRNA there were strong nucleotide preferences at specific positions, most notably positions 11 (G or C) and 19 (T) of the siRNA duplex. Expand
Rational siRNA design for RNA interference
TLDR
Application of an algorithm incorporating all eight characteristics associated with siRNA functionality significantly improves potent siRNA selection and highlights the utility of rational design for selecting potent siRNAs and facilitating functional gene knockdown studies. Expand
A large-scale RNAi screen in human cells identifies new components of the p53 pathway
TLDR
The construction of a set of retroviral vectors encoding 23,742 distinct shRNAs, which target 7,914 different human genes for suppression, is reported, which confers resistance to both p53-dependent and p19ARF-dependent proliferation arrest, and abolishes a DNA-damage-induced G1 cell-cycle arrest. Expand
An endoribonuclease-prepared siRNA screen in human cells identifies genes essential for cell division
TLDR
This study uncovers new aspects of cell division and establishes esiRNA as a versatile approach for genomic RNAi screens in mammalian cells. Expand
Sequence, chemical, and structural variation of small interfering RNAs and short hairpin RNAs and the effect on mammalian gene silencing.
TLDR
RNase-protecting phosphorothioate and 2'-fluoropyrimidine RNA backbone modifications of siRNAs did not significantly affect silencing efficiency, although cytotoxic effects were observed when every second phosphate of an siRNA duplex was replaced by phosphorOTHioate. Expand
Independent combinatorial effect of antisense oligonucleotides and RNAi-mediated specific inhibition of the recombinant rat P2X3 receptor.
TLDR
This is the first investigation at the molecular level of the potential benefits of mixed antisense and RNAi-mediated treatment for inhibiting expression of a medically relevant pain-related gene. Expand
Computational antisense oligo prediction with a neural network model
TLDR
This model can predict effective AOs (>50% inhibition of gene expression) with a success rate of 92%. Expand
A comparison of siRNA efficacy predictors.
TLDR
It is shown that the regularized genetic programming algorithm GPboost appears to have a higher and more stable performance than other algorithms on the collected datasets, and that other features that have been suggested to be important may be indirectly captured by the sequence. Expand
Artificial neural network prediction of antisense oligodeoxynucleotide activity.
TLDR
A predictive artificial neural network system for mapping tetranucleotide motif content to antisense oligo activity, trained for high-specificity prediction, that identifies the most likely oligo targets and provides estimates of the probabilities that oligos targeted against these sites will be effective. Expand
...
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3
4
...