100 research outputs found

    Building multiclass classifiers for remote homology detection and fold recognition

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    BACKGROUND: Protein remote homology detection and fold recognition are central problems in computational biology. Supervised learning algorithms based on support vector machines are currently one of the most effective methods for solving these problems. These methods are primarily used to solve binary classification problems and they have not been extensively used to solve the more general multiclass remote homology prediction and fold recognition problems. RESULTS: We present a comprehensive evaluation of a number of methods for building SVM-based multiclass classification schemes in the context of the SCOP protein classification. These methods include schemes that directly build an SVM-based multiclass model, schemes that employ a second-level learning approach to combine the predictions generated by a set of binary SVM-based classifiers, and schemes that build and combine binary classifiers for various levels of the SCOP hierarchy beyond those defining the target classes. CONCLUSION: Analyzing the performance achieved by the different approaches on four different datasets we show that most of the proposed multiclass SVM-based classification approaches are quite effective in solving the remote homology prediction and fold recognition problems and that the schemes that use predictions from binary models constructed for ancestral categories within the SCOP hierarchy tend to not only lead to lower error rates but also reduce the number of errors in which a superfamily is assigned to an entirely different fold and a fold is predicted as being from a different SCOP class. Our results also show that the limited size of the training data makes it hard to learn complex second-level models, and that models of moderate complexity lead to consistently better results

    A study of hierarchical and flat classification of proteins

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    Automatic classification of proteins using machine learning is an important problem that has received significant attention in the literature. One feature of this problem is that expert-defined hierarchies of protein classes exist and can potentially be exploited to improve classification performance. In this article we investigate empirically whether this is the case for two such hierarchies. We compare multi-class classification techniques that exploit the information in those class hierarchies and those that do not, using logistic regression, decision trees, bagged decision trees, and support vector machines as the underlying base learners. In particular, we compare hierarchical and flat variants of ensembles of nested dichotomies. The latter have been shown to deliver strong classification performance in multi-class settings. We present experimental results for synthetic, fold recognition, enzyme classification, and remote homology detection data. Our results show that exploiting the class hierarchy improves performance on the synthetic data, but not in the case of the protein classification problems. Based on this we recommend that strong flat multi-class methods be used as a baseline to establish the benefit of exploiting class hierarchies in this area

    Classification of protein interaction sentences via gaussian processes

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    The increase in the availability of protein interaction studies in textual format coupled with the demand for easier access to the key results has lead to a need for text mining solutions. In the text processing pipeline, classification is a key step for extraction of small sections of relevant text. Consequently, for the task of locating protein-protein interaction sentences, we examine the use of a classifier which has rarely been applied to text, the Gaussian processes (GPs). GPs are a non-parametric probabilistic analogue to the more popular support vector machines (SVMs). We find that GPs outperform the SVM and na\"ive Bayes classifiers on binary sentence data, whilst showing equivalent performance on abstract and multiclass sentence corpora. In addition, the lack of the margin parameter, which requires costly tuning, along with the principled multiclass extensions enabled by the probabilistic framework make GPs an appealing alternative worth of further adoption

    Combining classifiers for improved classification of proteins from sequence or structure

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    <p>Abstract</p> <p>Background</p> <p>Predicting a protein's structural or functional class from its amino acid sequence or structure is a fundamental problem in computational biology. Recently, there has been considerable interest in using discriminative learning algorithms, in particular support vector machines (SVMs), for classification of proteins. However, because sufficiently many positive examples are required to train such classifiers, all SVM-based methods are hampered by limited coverage.</p> <p>Results</p> <p>In this study, we develop a hybrid machine learning approach for classifying proteins, and we apply the method to the problem of assigning proteins to structural categories based on their sequences or their 3D structures. The method combines a full-coverage but lower accuracy nearest neighbor method with higher accuracy but reduced coverage multiclass SVMs to produce a full coverage classifier with overall improved accuracy. The hybrid approach is based on the simple idea of "punting" from one method to another using a learned threshold.</p> <p>Conclusion</p> <p>In cross-validated experiments on the SCOP hierarchy, the hybrid methods consistently outperform the individual component methods at all levels of coverage.</p> <p>Code and data sets are available at <url>http://noble.gs.washington.edu/proj/sabretooth</url></p

    Algorithms for feature selection and pattern recognition on Grassmann manifolds

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    Includes bibliographical references.2015 Summer.This dissertation presents three distinct application-driven research projects united by ideas and topics from geometric data analysis, optimization, computational topology, and machine learning. We first consider hyperspectral band selection problem solved by using sparse support vector machines (SSVMs). A supervised embedded approach is proposed using the property of SSVMs to exhibit a model structure that includes a clearly identifiable gap between zero and non-zero feature vector weights that permits important bands to be definitively selected in conjunction with the classification problem. An SSVM is trained using bootstrap aggregating to obtain a sample of SSVM models to reduce variability in the band selection process. This preliminary sample approach for band selection is followed by a secondary band selection which involves retraining the SSVM to further reduce the set of bands retained. We propose and compare three adaptations of the SSVM band selection algorithm for the multiclass problem. We illustrate the performance of these methods on two benchmark hyperspectral data sets. Second, we propose an approach for capturing the signal variability in data using the framework of the Grassmann manifold (Grassmannian). Labeled points from each class are sampled and used to form abstract points on the Grassmannian. The resulting points have representations as orthonormal matrices and as such do not reside in Euclidean space in the usual sense. There are a variety of metrics which allow us to determine distance matrices that can be used to realize the Grassmannian as an embedding in Euclidean space. Multidimensional scaling (MDS) determines a low dimensional Euclidean embedding of the manifold, preserving or approximating the Grassmannian geometry based on the distance measure. We illustrate that we can achieve an isometric embedding of the Grassmann manifold using the chordal metric while this is not the case with other distances. However, non-isometric embeddings generated by using the smallest principal angle pseudometric on the Grassmannian lead to the best classification results: we observe that as the dimension of the Grassmannian grows, the accuracy of the classification grows to 100% in binary classification experiments. To build a classification model, we use SSVMs to perform simultaneous dimension selection. The resulting classifier selects a subset of dimensions of the embedding without loss in classification performance. Lastly, we present an application of persistent homology to the detection of chemical plumes in hyperspectral movies. The pixels of the raw hyperspectral data cubes are mapped to the geometric framework of the Grassmann manifold where they are analyzed, contrasting our approach with the more standard framework in Euclidean space. An advantage of this approach is that it allows the time slices in a hyperspectral movie to be collapsed to a sequence of points in such a way that some of the key structure within and between the slices is encoded by the points on the Grassmannian. This motivates the search for topological structure, associated with the evolution of the frames of a hyperspectral movie, within the corresponding points on the manifold. The proposed framework affords the processing of large data sets, such as the hyperspectral movies explored in this investigation, while retaining valuable discriminative information. For a particular choice of a distance metric on the Grassmannian, it is possible to generate topological signals that capture changes in the scene after a chemical release

    Probabilistic multiple kernel learning

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    The integration of multiple and possibly heterogeneous information sources for an overall decision-making process has been an open and unresolved research direction in computing science since its very beginning. This thesis attempts to address parts of that direction by proposing probabilistic data integration algorithms for multiclass decisions where an observation of interest is assigned to one of many categories based on a plurality of information channels

    Fast protein superfamily classification using principal component null space analysis.

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    The protein family classification problem, which consists of determining the family memberships of given unknown protein sequences, is very important for a biologist for many practical reasons, such as drug discovery, prediction of molecular functions and medical diagnosis. Neural networks and Bayesian methods have performed well on the protein classification problem, achieving accuracy ranging from 90% to 98% while running relatively slowly in the learning stage. In this thesis, we present a principal component null space analysis (PCNSA) linear classifier to the problem and report excellent results compared to those of neural networks and support vector machines. The two main parameters of PCNSA are linked to the high dimensionality of the dataset used, and were optimized in an exhaustive manner to maximize accuracy. Paper copy at Leddy Library: Theses & Major Papers - Basement, West Bldg. / Call Number: Thesis2005 .F74. Source: Masters Abstracts International, Volume: 44-03, page: 1400. Thesis (M.Sc.)--University of Windsor (Canada), 2005

    DescFold: A web server for protein fold recognition

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    <p>Abstract</p> <p>Background</p> <p>Machine learning-based methods have been proven to be powerful in developing new fold recognition tools. In our previous work [Zhang, Kochhar and Grigorov (2005) <it>Protein Science</it>, <b>14</b>: 431-444], a machine learning-based method called DescFold was established by using Support Vector Machines (SVMs) to combine the following four descriptors: a profile-sequence-alignment-based descriptor using Psi-blast <it>e</it>-values and bit scores, a sequence-profile-alignment-based descriptor using Rps-blast <it>e</it>-values and bit scores, a descriptor based on secondary structure element alignment (SSEA), and a descriptor based on the occurrence of PROSITE functional motifs. In this work, we focus on the improvement of DescFold by incorporating more powerful descriptors and setting up a user-friendly web server.</p> <p>Results</p> <p>In seeking more powerful descriptors, the profile-profile alignment score generated from the COMPASS algorithm was first considered as a new descriptor (i.e., PPA). When considering a profile-profile alignment between two proteins in the context of fold recognition, one protein is regarded as a template (i.e., its 3D structure is known). Instead of a sequence profile derived from a Psi-blast search, a structure-seeded profile for the template protein was generated by searching its structural neighbors with the assistance of the TM-align structural alignment algorithm. Moreover, the COMPASS algorithm was used again to derive a profile-structural-profile-alignment-based descriptor (i.e., PSPA). We trained and tested the new DescFold in a total of 1,835 highly diverse proteins extracted from the SCOP 1.73 version. When the PPA and PSPA descriptors were introduced, the new DescFold boosts the performance of fold recognition substantially. Using the SCOP_1.73_40% dataset as the fold library, the DescFold web server based on the trained SVM models was further constructed. To provide a large-scale test for the new DescFold, a stringent test set of 1,866 proteins were selected from the SCOP 1.75 version. At a less than 5% false positive rate control, the new DescFold is able to correctly recognize structural homologs at the fold level for nearly 46% test proteins. Additionally, we also benchmarked the DescFold method against several well-established fold recognition algorithms through the LiveBench targets and Lindahl dataset.</p> <p>Conclusions</p> <p>The new DescFold method was intensively benchmarked to have very competitive performance compared with some well-established fold recognition methods, suggesting that it can serve as a useful tool to assist in template-based protein structure prediction. The DescFold server is freely accessible at <url>http://202.112.170.199/DescFold/index.html</url>.</p

    Combining Structure and Sequence Information Allows Automated Prediction of Substrate Specificities within Enzyme Families

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    An important aspect of the functional annotation of enzymes is not only the type of reaction catalysed by an enzyme, but also the substrate specificity, which can vary widely within the same family. In many cases, prediction of family membership and even substrate specificity is possible from enzyme sequence alone, using a nearest neighbour classification rule. However, the combination of structural information and sequence information can improve the interpretability and accuracy of predictive models. The method presented here, Active Site Classification (ASC), automatically extracts the residues lining the active site from one representative three-dimensional structure and the corresponding residues from sequences of other members of the family. From a set of representatives with known substrate specificity, a Support Vector Machine (SVM) can then learn a model of substrate specificity. Applied to a sequence of unknown specificity, the SVM can then predict the most likely substrate. The models can also be analysed to reveal the underlying structural reasons determining substrate specificities and thus yield valuable insights into mechanisms of enzyme specificity. We illustrate the high prediction accuracy achieved on two benchmark data sets and the structural insights gained from ASC by a detailed analysis of the family of decarboxylating dehydrogenases. The ASC web service is available at http://asc.informatik.uni-tuebingen.de/
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