Simulated Shape Data Research Articles

Extracting information from RNA SHAPE data: Kalman filtering approach.

RNA SHAPE experiments have become important and successful sources of information for RNA structure prediction. In such experiments, chemical reagents are used to probe RNA backbone flexibility at the nucleotide level, which in turn provides information on base pairing and therefore secondary structure. Little is known, however, about the statistics of such SHAPE data. In this work, we explore different representations of noise in SHAPE data and propose a statistically sound framework for extracting reliable reactivity information from multiple SHAPE replicates. Our analyses of RNA SHAPE experiments underscore that a normal noise model is not adequate to represent their data. We propose instead a log-normal representation of noise and discuss its relevance. Under this assumption, we observe that processing simulated SHAPE data by directly averaging different replicates leads to bias. Such bias can be reduced by analyzing the data following a log transformation, either by log-averaging or Kalman filtering. Application of Kalman filtering has the additional advantage that a prior on the nucleotide reactivities can be introduced. We show that the performance of Kalman filtering is then directly dependent on the quality of that prior. We conclude the paper with guidelines on signal processing of RNA SHAPE data.

How many landmarks are enough to characterize shape and size variation?

Accurate characterization of morphological variation is crucial for generating reliable results and conclusions concerning changes and differences in form. Despite the prevalence of landmark-based geometric morphometric (GM) data in the scientific literature, a formal treatment of whether sampled landmarks adequately capture shape variation has remained elusive. Here, I introduce LaSEC (Landmark Sampling Evaluation Curve), a computational tool to assess the fidelity of morphological characterization by landmarks. This task is achieved by calculating how subsampled data converge to the pattern of shape variation in the full dataset as landmark sampling is increased incrementally. While the number of landmarks needed for adequate shape variation is dependent on individual datasets, LaSEC helps the user (1) identify under- and oversampling of landmarks; (2) assess robustness of morphological characterization; and (3) determine the number of landmarks that can be removed without compromising shape information. In practice, this knowledge could reduce time and cost associated with data collection, maintain statistical power in certain analyses, and enable the incorporation of incomplete, but important, specimens to the dataset. Results based on simulated shape data also reveal general properties of landmark data, including statistical consistency where sampling additional landmarks has the tendency to asymptotically improve the accuracy of morphological characterization. As landmark-based GM data become more widely adopted, LaSEC provides a systematic approach to evaluate and refine the collection of shape data––a goal paramount for accumulation and analysis of accurate morphological information.

Evaluating the quality of SHAPE data simulated by k-mers for RNA structure prediction.

Finding an effective measure to predict a more accurate RNA secondary structure is a challenging problem. In the last decade, an experimental method, known as selective [Formula: see text]-hydroxyl acylation analyzed by primer extension (SHAPE), was proposed to measure the tendency of forming a base pair for almost all nucleotides in an RNA sequence. These SHAPE reactivities are then utilized to improve the accuracy of RNA structure prediction. Due to a significant impact of SHAPE reactivity and in order to reduce the experimental costs, we propose a new model called HL-k-mer. This model simulates the SHAPE reactivity for each nucleotide in an RNA sequence. This is done by fetching the SHAPE reactivities for all sub-sequences of length k (k-mers) appearing in helix and loop regions. For evaluating the quality of simulated SHAPE data, ESD-Fold method is used based on the SHAPE data simulated by the HL-k-mer model ([Formula: see text]). Also, for further evaluation of simulated SHAPE data, three different methods are employed. We also extend this model to simulate the SHAPE data for the RNA pseudoknotted structure. The results indicate that the average accuracies of prediction using the SHAPE data simulated by our models (for [Formula: see text]) are higher compared to the experimental SHAPE data.

RNA design using simulated SHAPE data.

It has long been established that in addition to being involved in protein translation, RNA plays essential roles in numerous other cellular processes, including gene regulation and DNA replication. Such roles are known to be dictated by higher-order structures of RNA molecules. It is therefore of prime importance to find an RNA sequence that can fold to acquire a particular function that is desirable for use in pharmaceuticals and basic research. The challenge of finding an RNA sequence for a given structure is known as the RNA design problem. Although there are several algorithms to solve this problem, they mainly consider hard constraints, such as minimum free energy, to evaluate the predicted sequences. Recently, SHAPE data has emerged as a new soft constraint for RNA secondary structure prediction. To take advantage of this new experimental constraint, we report here a new method for accurate design of RNA sequences based on their secondary structures using SHAPE data as pseudo-free energy. We then compare our algorithm with four others: INFO-RNA, ERD, MODENA and RNAifold 2.0. Our algorithm precisely predicts 26 out of 29 new sequences for the structures extracted from the Rfam dataset, while the other four algorithms predict no more than 22 out of 29. The proposed algorithm is comparable to the above algorithms on RNA-SSD datasets, where they can predict up to 33 appropriate sequences for RNA secondary structures out of 34.

Evolutionary Algorithm for RNA Secondary Structure Prediction Based on Simulated SHAPE Data.

BackgroundNon-coding RNAs perform a wide range of functions inside the living cells that are related to their structures. Several algorithms have been proposed to predict RNA secondary structure based on minimum free energy. Low prediction accuracy of these algorithms indicates that free energy alone is not sufficient to predict the functional secondary structure. Recently, the obtained information from the SHAPE experiment greatly improves the accuracy of RNA secondary structure prediction by adding this information to the thermodynamic free energy as pseudo-free energy.MethodIn this paper, a new method is proposed to predict RNA secondary structure based on both free energy and SHAPE pseudo-free energy. For each RNA sequence, a population of secondary structures is constructed and their SHAPE data are simulated. Then, an evolutionary algorithm is used to improve each structure based on both free and pseudo-free energies. Finally, a structure with minimum summation of free and pseudo-free energies is considered as the predicted RNA secondary structure.Results and ConclusionsComputationally simulating the SHAPE data for a given RNA sequence requires its secondary structure. Here, we overcome this limitation by employing a population of secondary structures. This helps us to simulate the SHAPE data for any RNA sequence and consequently improves the accuracy of RNA secondary structure prediction as it is confirmed by our experiments. The source code and web server of our proposed method are freely available at http://mostafa.ut.ac.ir/ESD-Fold/.

On clustering shape data

ABSTRACTAmong the statistical methods to model stochastic behaviours of objects, clustering is a preliminary technique to recognize similar patterns within a group of observations in a data set. Various distances to measure differences among objects could be invoked to cluster data through numerous clustering methods. When variables in hand contain geometrical information of objects, such metrics should be adequately adapted. In fact, statistical methods for these typical data are endowed with a geometrical paradigm in a multivariate sense. In this paper, a procedure for clustering shape data is suggested employing appropriate metrics. Then, the best shape distance candidate as well as a suitable agglomerative method for clustering the simulated shape data are provided by considering cluster validation measures. The results are implemented in a real life application.

Statistical performance of tests for factor effects on the shape of objects with application in manufacturing

This article considers experiments in manufacturing where the response of interest is the geometric shape of a manufactured part and the goal is to determine whether the process settings varied during the experiment affect the resulting shape of the part. An approach in practice to determine factor effects is to estimate the form error of the part—if a standard definition of the form error of interest exists—and conduct an analysis of variance (ANOVA) on the form errors. Instead, we study the performance of several statistical shape analysis techniques to analyze this class of experiments. Simulated shape data were used to perform power comparisons for two- and three-dimensional shapes. The ANOVA on the form errors was found to have a poor performance in detecting mean shape differences in circular and cylindrical shapes. Procrustes-based tests such as an ANOVA test due to Goodall and a recently proposed ANOVA permutation test provide the highest power to detect differences in the mean shape. These tests can also be applied to parts produced in “free form” manufacturing, where no standard definition of form error exists, provided that correspondent points exist on each part.

A surface-based approach for classification of 3D neuroanatomic structures

We present a new framework for 3D surface object classification that combines a powerful shape description method with suitable pattern classification techniques. Spherical harmonic parameterization and normalization techniques are used to describe a surface shape and derive a dual high dimensional landmark representation. A point distribution model is applied to reduce the dimensionality. Fisher's linear discriminants and support vector machines are used for classification. Several feature selection schemes are proposed for learning better classifiers. After showing the effectiveness of this framework using simulated shape data, we apply it to real hippocampal data in schizophrenia and perform extensive experimental studies by examining different combinations of techniques. We achieve best leave-one-out cross-validation accuracies of 93% (whole set, N = 56) and 90% (right-handed males, N = 39), respectively, which are competitive with the best results in previous studies using different techniques on similar types of data. Furthermore, to help medical diagnosis in practice, we employ a threshold-free receiver operating characteristic (ROC) approach as an alternative evaluation of classification results as well as propose a new method for visualizing discriminative patterns.