scholarly journals RNAfamProb Plus NeoFold: Estimations of Posterior Probabilities on RNA Structural Alignment and RNA Secondary Structures with Incorporating Homologous-RNA Sequences

2019 ◽  
Author(s):  
Masaki Tagashira ◽  
Kiyoshi Asai
Keyword(s):  
Secondary Structure ◽  
Sequence Alignment ◽  
Structural Alignment ◽  
Secondary Structures ◽  
Simultaneous Optimization ◽  
Supplementary Information ◽  
Sequence Alignments ◽  
Rna Sequences ◽  
Link Type ◽  
Rna Structural Alignment

AbstractMotivationThe simultaneous optimization of the sequence alignment and secondary structures among RNAs, structural alignment, has been required for the more appropriate comparison of functional ncRNAs than sequence alignment. Pseudo-probabilities given RNA sequences on structural alignment have been desired for more-accurate secondary structures, sequence alignments, consensus secondary structures, and structural alignments. However, any algorithms have not been proposed for these pseudo-probabilities.ResultsWe invented the RNAfamProb algorithm, an algorithm for estimating these pseudo-probabilities. We performed the application of these pseudo-probabilities to two biological problems, the visualization with these pseudo-probabilities and maximum-expected-accuracy secondary-structure (estimation). The RNAfamProb program, an implementation of this algorithm, plus the NeoFold program, a maximum-expected-accuracy secondary-structure program with these pseudo-probabilities, demonstrated prediction accuracy better than three state-of-the-art programs of maximum-expected-accuracy secondary-structure while demanding running time far longer than these three programs as expected due to the intrinsic serious problem-complexity of structural alignment compared with independent secondary structure and sequence alignment. Both the RNAfamProb and NeoFold programs estimate matters more accurately with incorporating homologous-RNA sequences.AvailabilityThe source code of each of these two programs is available on each of “https://github.com/heartsh/rnafamprob” and “https://github.com/heartsh/neofold”.Contact“[email protected]” and “[email protected]”.Supplementary informationSupplementary data are available at Bioinformatics online.

scholarly journals PhyloFold: Precise and Swift Prediction of RNA Secondary Structures to Incorporate Phylogeny among Homologs

2020 ◽  
Author(s):  
Masaki Tagashira
Keyword(s):  
Secondary Structure ◽  
Rna Secondary Structure ◽  
Prediction Accuracy ◽  
Structural Alignment ◽  
Source Code ◽  
Secondary Structures ◽  
Supplementary Information ◽  
Supplementary Data ◽  
Link Type ◽  
Structural Alignments

AbstractMotivationThe simultaneous consideration of sequence alignment and RNA secondary structure, or structural alignment, is known to help predict more accurate secondary structures of homologs. However, the consideration is heavy and can be done only roughly to decompose structural alignments.ResultsThe PhyloFold method, which predicts secondary structures of homologs considering likely pairwise structural alignments, was developed in this study. The method shows the best prediction accuracy while demanding comparable running time compared to conventional methods.AvailabilityThe source code of the programs implemented in this study is available on “https://github.com/heartsh/phylofold” and “https://github.com/heartsh/phyloalifold“.Contact“[email protected]”.Supplementary informationSupplementary data are available.

TOPAS: network-based structural alignment of RNA sequences

2019 ◽  
Vol 35 (17) ◽  
pp. 2941-2948 ◽  
Author(s):  
Chun-Chi Chen ◽  
Hyundoo Jeong ◽  
Xiaoning Qian ◽  
Byung-Jun Yoon
Keyword(s):  
Computational Complexity ◽  
Secondary Structure ◽  
Large Scale ◽  
Structural Alignment ◽  
Programming Approach ◽  
Rna Sequences ◽  
Optimal Sequence ◽  
Dynamic Programming Approach ◽  
Probabilistic Network ◽  
Rna Structural Alignment

Abstract Motivation For many RNA families, the secondary structure is known to be better conserved among the member RNAs compared to the primary sequence. For this reason, it is important to consider the underlying folding structures when aligning RNA sequences, especially for those with relatively low sequence identity. Given a set of RNAs with unknown structures, simultaneous RNA alignment and folding algorithms aim to accurately align the RNAs by jointly predicting their consensus secondary structure and the optimal sequence alignment. Despite the improved accuracy of the resulting alignment, the computational complexity of simultaneous alignment and folding for a pair of RNAs is O(N6), which is too costly to be used for large-scale analysis. Results In order to address this shortcoming, in this work, we propose a novel network-based scheme for pairwise structural alignment of RNAs. The proposed algorithm, TOPAS, builds on the concept of topological networks that provide structural maps of the RNAs to be aligned. For each RNA sequence, TOPAS first constructs a topological network based on the predicted folding structure, which consists of sequential edges and structural edges weighted by the base-pairing probabilities. The obtained networks can then be efficiently aligned by using probabilistic network alignment techniques, thereby yielding the structural alignment of the RNAs. The computational complexity of our proposed method is significantly lower than that of the Sankoff-style dynamic programming approach, while yielding favorable alignment results. Furthermore, another important advantage of the proposed algorithm is its capability of handling RNAs with pseudoknots while predicting the RNA structural alignment. We demonstrate that TOPAS generally outperforms previous RNA structural alignment methods on RNA benchmarks in terms of both speed and accuracy. Availability and implementation Source code of TOPAS and the benchmark data used in this paper are available at https://github.com/bjyoontamu/TOPAS.

scholarly journals RNAcmap: A Fully Automatic Method for Predicting Contact Maps of RNAs by Evolutionary Coupling Analysis

2020 ◽  
Author(s):  
Tongchuan Zhang ◽  
Jaswinder Singh ◽  
Thomas Litfin ◽  
Jian Zhan ◽  
Kuldip Paliwal ◽  
...  
Keyword(s):  
Secondary Structure ◽  
Structure Prediction ◽  
Automatic Method ◽  
Sequence Alignments ◽  
Coupling Analysis ◽  
Rna Sequences ◽  
Homologous Sequences ◽  
Link Type ◽  
Fully Automatic ◽  
Evolutionary Coupling

AbstractMotivationThe accuracy of RNA secondary and tertiary structure prediction can be significantly improved by using structural restraints derived from evolutionary or direct coupling analysis. Currently, these coupling analyses relied on manually curated multiple sequence alignments collected in the Rfam database, which contains 3016 families. By comparison, millions of non-coding RNA sequences are known. Here, we established RNAcmap, a fully automatic method that enables evolutionary coupling analysis for any RNA sequences. The homology search was based on the covariance model built by Infernal according to two secondary structure predictors: a folding-based algorithm RNAfold and the latest deep-learning method SPOT-RNA.ResultsWe show that the performance of RNAcmap is less dependent on the specific evolutionary coupling tool but is more dependent on the accuracy of secondary structure predictor with the best performance given by RNAcmap (SPOT-RNA). The performance of RNAcmap (SPOT-RNA) is comparable to that based on Rfam-supplied alignment and consistent for those sequences that are not in Rfam collections. Further improvement can be made with a simple meta predictor RNAcmap (SPOT-RNA/RNAfold) depending on which secondary structure predictor can find more homologous sequences. Reliable base-pairing information generated from RNAcmap, for RNAs with high effective homologous sequences, in particular, will be useful for aiding RNA structure prediction.Availability and implementationRNAcmap is available as a web server at https://sparks-lab.org/server/rnacmap/) and as a standalone application along with the datasets at https://github.com/sparks-lab-org/RNAcmap.

scholarly journals Predicting Consensus Structures for RNA Alignments via Pseudo-Energy Minimization

2009 ◽  
Vol 3 ◽  
pp. BBI.S2578 ◽  
Author(s):  
Junilda Spirollari ◽  
Jason T.L. Wang ◽  
Kaizhong Zhang ◽  
Vivian Bellofatto ◽  
Yongkyu Park ◽  
...  
Keyword(s):  
Free Energy ◽  
Secondary Structure ◽  
Sequence Alignment ◽  
Multiple Sequence Alignment ◽  
Energy Minimization ◽  
Secondary Structure Prediction ◽  
Sequence Alignments ◽  
Rna Sequences ◽  
Multiple Sequence ◽  
Consensus Secondary Structure

Thermodynamic processes with free energy parameters are often used in algorithms that solve the free energy minimization problem to predict secondary structures of single RNA sequences. While results from these algorithms are promising, an observation is that single sequence-based methods have moderate accuracy and more information is needed to improve on RNA secondary structure prediction, such as covariance scores obtained from multiple sequence alignments. We present in this paper a new approach to predicting the consensus secondary structure of a set of aligned RNA sequences via pseudo-energy minimization. Our tool, called RSpredict, takes into account sequence covariation and employs effective heuristics for accuracy improvement. RSpredict accepts, as input data, a multiple sequence alignment in FASTA or ClustalW format and outputs the consensus secondary structure of the input sequences in both the Vienna style Dot Bracket format and the Connectivity Table format. Our method was compared with some widely used tools including KNetFold, Pfold and RNAalifold. A comprehensive test on different datasets including Rfam sequence alignments and a multiple sequence alignment obtained from our study on the Drosophila X chromosome reveals that RSpredict is competitive with the existing tools on the tested datasets. RSpredict is freely available online as a web server and also as a jar file for download at http://datalab.njit.edu/biology/RSpredict .

scholarly journals Benchmarking Statistical Multiple Sequence Alignment

2018 ◽  
Author(s):  
Michael Nute ◽  
Ehsan Saleh ◽  
Tandy Warnow
Keyword(s):  
Sequence Alignment ◽  
Multiple Sequence Alignment ◽  
Structural Alignment ◽  
Estimation Method ◽  
Simulated Data ◽  
Protein Sequences ◽  
Data Sets ◽  
Sequence Alignments ◽  
Multiple Sequence ◽  
Simulated Data Sets

AbstractThe estimation of multiple sequence alignments of protein sequences is a basic step in many bioinformatics pipelines, including protein structure prediction, protein family identification, and phylogeny estimation. Statistical co-estimation of alignments and trees under stochastic models of sequence evolution has long been considered the most rigorous technique for estimating alignments and trees, but little is known about the accuracy of such methods on biological benchmarks. We report the results of an extensive study evaluating the most popular protein alignment methods as well as the statistical co-estimation method BAli-Phy on 1192 protein data sets from established benchmarks as well as on 120 simulated data sets. Our study (which used more than 230 CPU years for the BAli-Phy analyses alone) shows that BAli-Phy is dramatically more accurate than the other alignment methods on the simulated data sets, but is among the least accurate on the biological benchmarks. There are several potential causes for this discordance, including model misspecification, errors in the reference alignments, and conflicts between structural alignment and evolutionary alignments; future research is needed to understand the most likely explanation for our observations. multiple sequence alignment, BAli-Phy, protein sequences, structural alignment, homology

scholarly journals Sequence alignment using machine learning for accurate template-based protein structure prediction

2019 ◽  
Vol 36 (1) ◽  
pp. 104-111
Author(s):  
Shuichiro Makigaki ◽  
Takashi Ishida
Keyword(s):  
Machine Learning ◽  
Structure Prediction ◽  
Tertiary Structure ◽  
Structural Alignment ◽  
Protein Structures ◽  
Substitution Matrix ◽  
Detection Methods ◽  
Supplementary Information ◽  
Homology Detection ◽  
Sequence Alignments

Abstract Motivation Template-based modeling, the process of predicting the tertiary structure of a protein by using homologous protein structures, is useful if good templates can be found. Although modern homology detection methods can find remote homologs with high sensitivity, the accuracy of template-based models generated from homology-detection-based alignments is often lower than that from ideal alignments. Results In this study, we propose a new method that generates pairwise sequence alignments for more accurate template-based modeling. The proposed method trains a machine learning model using the structural alignment of known homologs. It is difficult to directly predict sequence alignments using machine learning. Thus, when calculating sequence alignments, instead of a fixed substitution matrix, this method dynamically predicts a substitution score from the trained model. We evaluate our method by carefully splitting the training and test datasets and comparing the predicted structure’s accuracy with that of state-of-the-art methods. Our method generates more accurate tertiary structure models than those produced from alignments obtained by other methods. Availability and implementation https://github.com/shuichiro-makigaki/exmachina. Supplementary information Supplementary data are available at Bioinformatics online.

QuanTest2: benchmarking multiple sequence alignments using secondary structure prediction

2019 ◽  
Author(s):  
Fabian Sievers ◽  
Desmond G Higgins
Keyword(s):  
Secondary Structure ◽  
Structure Prediction ◽  
Secondary Structure Prediction ◽  
Reference Sequence ◽  
Supplementary Information ◽  
Sequence Alignments ◽  
Multiple Sequence ◽  
Multiple Sequence Alignments ◽  
Reference Sequences ◽  
Selection Of

Abstract Motivation Secondary structure prediction accuracy (SSPA) in the QuanTest benchmark can be used to measure accuracy of a multiple sequence alignment. SSPA correlates well with the sum-of-pairs score, if the results are averaged over many alignments but not on an alignment-by-alignment basis. This is due to a sub-optimal selection of reference and non-reference sequences in QuanTest. Results We develop an improved strategy for selecting reference and non-reference sequences for a new benchmark, QuanTest2. In QuanTest2, SSPA and SP correlate better on an alignment-by-alignment basis than in QuanTest. Guide-trees for QuanTest2 are more balanced with respect to reference sequences than in QuanTest. QuanTest2 scores correlate well with other well-established benchmarks. Availability and implementation QuanTest2 is available at http://bioinf.ucd.ie/quantest2.tar, comprises of reference and non-reference sequence sets and a scoring script. Supplementary information Supplementary data are available at Bioinformatics online

scholarly journals Exponentially few RNA structures are designable

2019 ◽  
Author(s):  
Hua-Ting Yao ◽  
Mireille Regnier ◽  
Cedric Chauve ◽  
Yann Ponty
Keyword(s):  
Secondary Structure ◽  
Secondary Structures ◽  
Rna Structures ◽  
Folding Model ◽  
Rna Sequences ◽  
Rna Sequence ◽  
Energy Models ◽  
Rna Design ◽  
Additional Constraints ◽  
Alternative Structure

ABSTRACTThe problem of RNA design attempts to construct RNA sequences that perform a predefined biological function, identified by several additional constraints. One of the foremost objective of RNA design is that the designed RNA sequence should adopt a predefined target secondary structure preferentially to any alternative structure, according to a given metrics and folding model. It was observed in several works that some secondary structures are undesignable, i.e. no RNA sequence can fold into the target structure while satisfying some criterion measuring how preferential this folding is compared to alternative conformations.In this paper, we show that the proportion of designable secondary structures decreases exponentially with the size of the target secondary structure, for various popular combinations of energy models and design objectives. This exponential decay is, at least in part, due to the existence of undesignable motifs, which can be generically constructed, and jointly analyzed to yield asymptotic upper-bounds on the number of designable structures.

scholarly journals MSAC: Compression of multiple sequence alignment files

2017 ◽  
Author(s):  
Sebastian Deorowicz ◽  
Joanna Walczyszyn ◽  
Agnieszka Debudaj-Grabysz
Keyword(s):  
Sequence Alignment ◽  
Compression Ratio ◽  
Multiple Sequence Alignment ◽  
Sequence Alignments ◽  
Multiple Sequence ◽  
Multiple Sequence Alignments ◽  
Link Type ◽  
Bioinformatics Databases ◽  
Supplementary Material ◽  
Burrows Wheeler Transform

AbstractMotivationBioinformatics databases grow rapidly and achieve values hardly to imagine a decade ago. Among numerous bioinformatics processes generating hundreds of GB is multiple sequence alignments of protein families. Its largest database, i.e., Pfam, consumes 40–230 GB, depending of the variant. Storage and transfer of such massive data has become a challenge.ResultsWe propose a novel compression algorithm, MSAC (Multiple Sequence Alignment Compressor), designed especially for aligned data. It is based on a generalisation of the positional Burrows–Wheeler transform for non-binary alphabets. MSAC handles FASTA, as well as Stockholm files. It offers up to six times better compression ratio than other commonly used compressors, i.e., gzip. Performed experiments resulted in an analysis of the influence of a protein family size on the compression ratio.AvailabilityMSAC is available for free at https://github.com/refresh-bio/msac and http://sun.aei.polsl.pl/REFRESH/[email protected] materialSupplementary data are available at the publisher Web site.

scholarly journals RNA inter-nucleotide 3D closeness prediction by deep residual neural networks

2020 ◽  
Author(s):  
Saisai Sun ◽  
Wenkai Wang ◽  
Zhenling Peng ◽  
Jianyi Yang
Keyword(s):  
Neural Networks ◽  
Secondary Structure ◽  
Rna Structure ◽  
Supplementary Information ◽  
Sequence Alignments ◽  
Multiple Sequence ◽  
Guide Rna ◽  
Multiple Sequence Alignments ◽  
Contact Distance ◽  
Distance Restraints

Abstract Motivation Recent years have witnessed that the inter-residue contact/distance in proteins could be accurately predicted by deep neural networks, which significantly improve the accuracy of predicted protein structure models. In contrast, fewer studies have been done for the prediction of RNA inter-nucleotide 3D closeness. Results We proposed a new algorithm named RNAcontact for the prediction of RNA inter-nucleotide 3D closeness. RNAcontact was built based on the deep residual neural networks. The covariance information from multiple sequence alignments and the predicted secondary structure were used as the input features of the networks. Experiments show that RNAcontact achieves the respective precisions of 0.8 and 0.6 for the top L/10 and L (where L is the length of an RNA) predictions on an independent test set, significantly higher than other evolutionary coupling methods. Analysis shows that about 1/3 of the correctly predicted 3D closenesses are not base pairings of secondary structure, which are critical to the determination of RNA structure. In addition, we demonstrated that the predicted 3D closeness could be used as distance restraints to guide RNA structure folding by the 3dRNA package. More accurate models could be built by using the predicted 3D closeness than the models without using 3D closeness. Availability and implementation The webserver and a standalone package are available at: http://yanglab.nankai.edu.cn/RNAcontact/. Contact [email protected] Supplementary information Supplementary data are available at Bioinformatics online.

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