With the explosive growth of biological sequences generated in the post-genomic era, one of the most challenging problems in bioinformatics and computational biology is to computationally characterize sequences, structures and functions in an efficient, accurate and high-throughput manner. A number of online web servers and stand-alone tools have been developed to address this to date; however, all these tools have their limitations and drawbacks in terms of their effectiveness, user-friendliness and capacity. Here, we present iLearn, a comprehensive and versatile Python-based toolkit, integrating the functionality of feature extraction, clustering, normalization, selection, dimensionality reduction, predictor construction, best descriptor/model selection, ensemble learning and results visualization for DNA, RNA and protein sequences. iLearn was designed for users that only want to upload their data set and select the functions they need calculated from it, while all necessary procedures and optimal settings are completed automatically by the software. iLearn includes a variety of descriptors for DNA, RNA and proteins, and four feature output formats are supported so as to facilitate direct output usage or communication with other computational tools. In total, iLearn encompasses 16 different types of feature clustering, selection, normalization and dimensionality reduction algorithms, and five commonly used machine-learning algorithms, thereby greatly facilitating feature analysis and predictor construction. iLearn is made freely available via an online web server and a stand-alone toolkit.

Motivation: Pseudoknots found in secondary structures of a number of functional RNAs play various roles in biological processes. Recent methods for predicting RNA secondary structures cover certain classes of pseudoknotted structures, but only a few of them achieve satisfying predictions in terms of both speed and accuracy. Results: We propose IPknot, a novel computational method for predicting RNA secondary structures with pseudoknots based on maximizing expected accuracy of a predicted structure. IPknot decomposes a pseudoknotted structure into a set of pseudoknot-free substructures and approximates a base-pairing probability distribution that considers pseudoknots, leading to the capability of modeling a wide class of pseudoknots and running quite fast. In addition, we propose a heuristic algorithm for refining base-paring probabilities to improve the prediction accuracy of IPknot. The problem of maximizing expected accuracy is solved by using integer programming with threshold cut. We also extend IPknot so that it can predict the consensus secondary structure with pseudoknots when a multiple sequence alignment is given. IPknot is validated through extensive experiments on various datasets, showing that IPknot achieves better prediction accuracy and faster running time as compared with several competitive prediction methods. Availability: The program of IPknot is available at http://www.ncrna.org/software/ipknot/. IPknot is also available as a web server at http://rna.naist.jp/ipknot/. Contact:satoken@k.u-tokyo.ac.jp; ykato@is.naist.jp Supplementary information: Supplementary data are available at Bioinformatics online.

Motivation: Remote homology detection between protein sequences is a central problem in computational biology. Discriminative methods involving support vector machines (SVMs) are currently the most effective methods for the problem of superfamily recognition in the Structural Classification Of Proteins (SCOP) database. The performance of SVMs depends critically on the kernel function used to quantify the similarity between sequences.

Motivation: Inferring genetic network architecture from time series data of gene expression patterns is an important topic in bioinformatics. Although inference algorithms based on the Boolean network were proposed, the Boolean network was not sufficient as a model of a genetic network. Results: First, a Boolean network model with noise is proposed, together with an inference algorithm for it. Next, a qualitative network model is proposed, in which regulation rules are represented as qualitative rules and embedded in the network structure. Algorithms are also presented for inferring qualitative relations from time series data. Then, an algorithm for inferring S-systems (synergistic and saturable systems) from time series data is presented, where S-systems are based on a particular kind of nonlinear differential equation and have been applied to the analysis of various biological systems. Theoretical results are shown for Boolean networks with noises and simple qualitative networks. Computational results are shown for Boolean networks with noises and S-systems, where real data are not used because the proposed models are still conceptual and the quantity and quality of currently available data are not enough for the application of the proposed methods. Contact: takutsu@ims.u-tokyo.ac.jp To whom correspondence should be addressed.