Bioinformatics Vol. 16 no. 7 2000
Pages 583-605
© 2000 Oxford University Press
Original Paper |
Secondary structure alone is generally not statistically significant for the detection of noncoding RNAs
1 Department of Genetics, Washington University, St. Louis, MO 63110, USA
Received on August 4, 1999
; revised on December 15, 1999
; accepted on December 21, 1999
Motivation: Several results in the literature suggest that biologically interesting RNAs have secondary structures that are more stable than expected by chance. Based on these observations, we developed a scanning algorithm for detecting noncoding RNA genes in genome sequences, using a fully probabilistic version of the Zuker minimum-energy folding algorithm.
Results: Preliminary results were encouraging, but certain anomalies led us to do a carefully controlled investigation of this class of methods. Ultimately, our results argue that for the probabilistic model there is indeed a statistical effect, but it comes mostly from local base-composition bias and not from RNA secondary structure. For the thermodynamic implementation (which evaluates statistical significance by doing Monte Carlo shuffling in fixed-length sequence windows, thus eliminating the base-composition effect) the signals for noncoding RNAs are still usually indistinguishable from noise, especially when certain statistical artifacts resulting from local base-composition inhomogeneity are taken into account. We conclude that although a distinct, stable secondary structure is undoubtedly important in most noncoding RNAs, the stability of most noncoding RNA secondary structures is not sufficiently different from the predicted stability of a random sequence to be useful as a general genefinding approach.
Contact: eddy{at}genetics.wustl.edu
* To whom correspondence should be addressed.
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