Prediction of mature microRNA and piwi-interacting RNA without a genome reference or precursors.

The discovery of novel microRNA (miRNA) and piwi-interacting RNA (piRNA) is an important task for the understanding of many biological processes. Most of the available miRNA and piRNA identification methods are dependent on the availability of the organism's genome sequence and the quality of its annotation. Therefore, an efficient prediction method based solely on the short RNA reads and requiring no genomic information is highly desirable. In this study, we propose an approach that relies primarily on the nucleotide composition of the read and does not require reference genomes of related species for prediction. Using an empirical Bayesian kernel method and the error correcting output codes framework, compact models suitable for large-scale analyses are built on databases of known mature miRNAs and piRNAs. We found that the usage of an L1-based Gaussian kernel can double the true positive rate compared to the standard L2-based Gaussian kernel. Our approach can increase the true positive rate by at most 60% compared to the existing piRNA predictor based on the analysis of a hold-out test set. Using experimental data, we also show that our approach can detect about an order of magnitude or more known miRNAs than the mature miRNA predictor, miRPlex.

Multiclass relevance units machine: benchmark evaluation and application to small ncRNA discovery.

BACKGROUND: Classification is the problem of assigning each input object to one of a finite number of classes. This problem has been extensively studied in machine learning and statistics, and there are numerous applications to bioinformatics as well as many other fields. Building a multiclass classifier has been a challenge, where the direct approach of altering the binary classification algorithm to accommodate more than two classes can be computationally too expensive. Hence the indirect approach of using binary decomposition has been commonly used, in which retrieving the class posterior probabilities from the set of binary posterior probabilities given by the individual binary classifiers has been a major issue. METHODS: In this work, we present an extension of a recently introduced probabilistic kernel-based learning algorithm called the Classification Relevance Units Machine (CRUM) to the multiclass setting to increase its applicability. The extension is achieved under the error correcting output codes framework. The probabilistic outputs of the binary CRUMs are preserved using a proposed linear-time decoding algorithm, an alternative to the generalized Bradley-Terry (GBT) algorithm whose application to large-scale prediction settings is prohibited by its computational complexity. The resulting classifier is called the Multiclass Relevance Units Machine (McRUM). RESULTS: The evaluation of McRUM on a variety of real small-scale benchmark datasets shows that our proposed Naïve decoding algorithm is computationally more efficient than the GBT algorithm while maintaining a similar level of predictive accuracy. Then a set of experiments on a larger scale dataset for small ncRNA classification have been conducted with Naïve McRUM and compared with the Gaussian and linear SVM. Although McRUM's predictive performance is slightly lower than the Gaussian SVM, the results show that the similar level of true positive rate can be achieved by sacrificing false positive rate slightly. Furthermore, McRUM is computationally more efficient than the SVM, which is an important factor for large-scale analysis. CONCLUSIONS: We have proposed McRUM, a multiclass extension of binary CRUM. McRUM with Naïve decoding algorithm is computationally efficient in run-time and its predictive performance is comparable to the well-known SVM, showing its potential in solving large-scale multiclass problems in bioinformatics and other fields of study.

Probabilistic Prediction of Protein Phosphorylation Sites Using Classification Relevance Units Machines.

Phosphorylation is an important post-translational modification of proteins that is essential to the regulation of many cellular processes. Although most of the phosphorylation sites discovered in protein sequences have been identified experimentally, the in vivo and in vitro discovery of the sites is an expensive, time-consuming and laborious task. Therefore, the development of computational methods for prediction of protein phosphorylation sites has drawn considerable attention. In this work, we present a kernel-based probabilistic Classification Relevance Units Machine (CRUM) for in silico phosphorylation site prediction. In comparison with the popular Support Vector Machine (SVM) CRUM shows comparable predictive performance and yet provides a more parsimonious model. This is desirable since it leads to a reduction in prediction run-time, which is important in predictions on large-scale data. Furthermore, the CRUM training algorithm has lower run-time and memory complexity and has a simpler parameter selection scheme than the Relevance Vector Machine (RVM) learning algorithm. To further investigate the viability of using CRUM in phosphorylation site prediction, we construct multiple CRUM predictors using different combinations of three phosphorylation site features - BLOSUM encoding, disorder, and amino acid composition. The predictors are evaluated through cross-validation and the results show that CRUM with BLOSUM feature is among the best performing CRUM predictors in both cross-validation and benchmark experiments. A comparative study with existing prediction tools in an independent benchmark experiment suggests possible direction for further improving the predictive performance of CRUM predictors.

Robotic-surgical instrument wrist pose estimation.

The Compact Lightweight Surgery Robot from the University of Hawaii includes two teleoperated instruments and one endoscope manipulator which act in accord to perform assisted interventional medicine. The relative positions and orientations of the robotic instruments and endoscope must be known to the teleoperation system so that the directions of the instrument motions can be controlled to correspond closely to the directions of the motions of the master manipulators, as seen by the the endoscope and displayed to the surgeon. If the manipulator bases are mounted in known locations and all manipulator joint variables are known, then the necessary coordinate transformations between the master and slave manipulators can be easily computed. The versatility and ease of use of the system can be increased, however, by allowing the endoscope or instrument manipulator bases to be moved to arbitrary positions and orientations without reinitializing each manipulator or remeasuring their relative positions. The aim of this work is to find the pose of the instrument end effectors using the video image from the endoscope camera. The P3P pose estimation algorithm is used with a Levenberg-Marquardt optimization to ensure convergence. The correct transformations between the master and slave coordinate frames can then be calculated and updated when the bases of the endoscope or instrument manipulators are moved to new, unknown, positions at any time before or during surgical procedures.

Inferring figure-ground using a recurrent integrate-and-fire neural circuit.

Several theories of early visual perception hypothesize neural circuits that are responsible for assigning ownership of an object's occluding contour to a region which represents the "figure." Previously, we have presented a Bayesian network model which integrates multiple cues and uses belief propagation to infer local figure-ground relationships along an object's occluding contour. In this paper, we use a linear integrate-and-fire model to demonstrate how such inference mechanisms could be carried out in a biologically realistic neural circuit. The circuit maps the membrane potentials of individual neurons to log probabilities and uses recurrent connections to represent transition probabilities. The network's "perception" of figure-ground is demonstrated for several examples, including perceptually ambiguous figures, and compared qualitatively and quantitatively with human psychophysics.

EM in high-dimensional spaces.

This paper considers fitting a mixture of Gaussians model to high-dimensional data in scenarios where there are fewer data samples than feature dimensions. Issues that arise when using principal component analysis (PCA) to represent Gaussian distributions inside Expectation-Maximization (EM) are addressed, and a practical algorithm results. Unlike other algorithms that have been proposed, this algorithm does not try to compress the data to fit low-dimensional models. Instead, it models Gaussian distributions in the (N - 1)-dimensional space spanned by the N data samples. We are able to show that this algorithm converges on data sets where low-dimensional techniques do not.

Integration of form and motion within a generative model of visual cortex.

One of the challenges faced by the visual system is integrating cues within and across processing streams for inferring scene properties and structure. This is particularly apparent in the inference of object motion, where psychophysical experiments have shown that integration of motion signals, distributed across space, must also be integrated with form cues. This has led several to conclude that there exist mechanisms which enable form cues to 'veto' or completely suppress ambiguous motion signals. We describe a probabilistic approach which uses a generative network model for integrating form and motion cues using the machinery of belief propagation and Bayesian inference. We show, using computer simulations, that motion integration can be mediated via a local, probabilistic representation of contour ownership, which we have previously termed 'direction of figure'. The uncertainty of this inferred form cue is used to modulate the covariance matrix of network nodes representing local motion estimates in the motion stream. We show with results for two sets of stimuli that the model does not completely suppress ambiguous cues, but instead integrates them in a way that is a function of their underlying uncertainty. The result is that the model can account for the continuum of bias seen for motion coherence and perceived object motion in psychophysical experiments.

Inferring direction of figure using a recurrent integrate-and-fire neural circuit.

Several theories of early visual perception hypothesize neural circuits that are responsible for assigning ownership of an object's occluding contour to a region which represents the "figure". Previously, we presented a Bayesian network model which integrates multiple cues and uses belief propagation to infer direction of figure (DOF) along an object's occluding contour. In this paper, we use a linear integrate-and-fire model to demonstrate how such inference mechanisms could be carried out in a biologically realistic neural circuit. The circuit, modeled after the network proposed by Rao, maps the membrane potentials of individual neurons to log probabilities and uses recurrent connections to represent transition probabilities. The network's "perception " of DOF is demonstrated for several examples, including perceptually ambiguous figures, with results qualitatively consistent with human perception.