FlexStem: improving predictions of RNA secondary structures with pseudoknots by reducing the search space

doi:10.1093/bioinformatics/btn327

	FlexStem: improving predictions of RNA secondary structures with pseudoknots by reducing the search space
	Chen, Xiang 1,2,3; He, Si-Min 1,2; Bu, Dongbo 1,2; Zhang, Fa 1,2; Wang, Zhiyong 4; Chen, Runsheng 5; Gao, Wen 6
	2008-09-15
发表期刊	BIOINFORMATICS
ISSN	1367-4803
卷号	24 期号:18 页码:1994-2001
摘要	Motivation: RNA secondary structures with pseudoknots are often predicted by minimizing free energy, which is proved to be NP-hard. Due to kinetic reasons the real RNA secondary structure often has local instead of global minimum free energy. This implies that we may improve the performance of RNA secondary structure prediction by taking kinetics into account and minimize free energy in a local area. Result: we propose a novel algorithm named FlexStem to predict RNA secondary structures with pseudoknots. Still based on MFE criterion, FlexStem adopts comprehensive energy models that allow complex pseudoknots. Unlike classical thermodynamic methods, our approach aims to simulate the RNA folding process by successive addition of maximal stems, reducing the search space while maintaining or even improving the prediction accuracy. This reduced space is constructed by our maximal stem strategy and stem-adding rule induced from elaborate statistical experiments on real RNA secondary structures. The strategy and the rule also reflect the folding characteristic of RNA from a new angle and help compensate for the deficiency of merely relying on MFE in RNA structure prediction. We validate FlexStem by applying it to tRNAs, 5SrRNAs and a large number of pseudoknotted structures and compare it with the well-known algorithms such as RNAfold, PKNOTS, PknotsRG, HotKnots and ILM according to their overall sensitivities and specificities, as well as positive and negative controls on pseudoknots. The results show that FlexStem significantly increases the prediction accuracy through its local search strategy.
DOI	10.1093/bioinformatics/btn327
收录类别	SCI
语种	英语
资助项目	National Key Basic R&D Program (973) of China[2002CB713807] ; Frontier Project of Knowledge Innovation Program of Chinese Academy of Sciences ; National Natural Science Foundation of China[90612019] ; National Natural Science Foundation of China[60503060]
WOS研究方向	Biochemistry & Molecular Biology ; Biotechnology & Applied Microbiology ; Computer Science ; Mathematical & Computational Biology ; Mathematics
WOS类目	Biochemical Research Methods ; Biotechnology & Applied Microbiology ; Computer Science, Interdisciplinary Applications ; Mathematical & Computational Biology ; Statistics & Probability
WOS记录号	WOS:000258959600004
出版者	OXFORD UNIV PRESS
引用统计	被引频次：30[WOS] [WOS记录] [WOS相关记录]
文献类型	期刊论文
条目标识符	http://119.78.100.204/handle/2XEOYT63/11412
专题	中国科学院计算技术研究所期刊论文_英文
通讯作者	Chen, Xiang
作者单位	1.Chinese Acad Sci, Key Lab Intelligent Informat Proc, Beijing 100190, Peoples R China 2.Chinese Acad Sci, Inst Comp Technol, Beijing 100190, Peoples R China 3.Chinese Acad Sci, Grad Univ, Beijing 100049, Peoples R China 4.Fudan Univ, Dept Comp Sci & Engn, Shanghai Key Lab Intelligent Informat Proc, Shanghai 200433, Peoples R China 5.Chinese Acad Sci, Inst Biophys, Beijing 100101, Peoples R China 6.Peking Univ, Sch Elect Engn & Comp Sci, Beijing 100871, Peoples R China
推荐引用方式 GB/T 7714	Chen, Xiang,He, Si-Min,Bu, Dongbo,et al. FlexStem: improving predictions of RNA secondary structures with pseudoknots by reducing the search space[J]. BIOINFORMATICS,2008,24(18):1994-2001.
APA	Chen, Xiang.,He, Si-Min.,Bu, Dongbo.,Zhang, Fa.,Wang, Zhiyong.,...&Gao, Wen.(2008).FlexStem: improving predictions of RNA secondary structures with pseudoknots by reducing the search space.BIOINFORMATICS,24(18),1994-2001.
MLA	Chen, Xiang,et al."FlexStem: improving predictions of RNA secondary structures with pseudoknots by reducing the search space".BIOINFORMATICS 24.18(2008):1994-2001.