7586216
Linear Regression Models for Solvent Accessibility Prediction in Proteins
The relative solvent accessibility (RSA) of an amino acid residue in a protein structure is a real number that represents the solvent exposed surface area of this residue in relative terms. The problem of predicting the RSA from the primary amino acid sequence can therefore be cast as a regression problem. Nevertheless, RSA prediction has so far typically been cast as a classification problem. Consequently, various machine learning techniques have been used within the classification framework to predict whether a given amino acid exceeds some (arbitrary) RSA threshold and would thus be predicted to be "exposed," as opposed to "buried." We have recently developed novel methods for RSA prediction using nonlinear regression techniques which provide accurate estimates of the real-valued RSA and outperform classification-based approaches with respect to commonly used two-class projections. However, while their performance seems to provide a significant improvement over previously published approaches, these Neural Network (NN) based methods are computationally expensive to train and involve several thousand parameters. In this work, we develop alternative regression models for RSA prediction which are computationally much less expensive, involve orders-of-magnitude fewer parameters, and are still competitive in terms of prediction quality. In particular, we investigate several regression models for RSA prediction using linear L1-support vector regression (SVR) approaches as well as standard linear least squares (LS) regression. Using rigorously derived validation sets of protein structures and extensive cross-validation analysis, we compare the performance of the SVR with that of LS regression and NN-based methods. In particular, we show that the flexibility of the SVR (as encoded by metaparameters such as the error insensitivity and the error penalization terms) can be very beneficial to optimize the prediction accuracy for buried residues. We conclude that the simple and computationally much more efficient linear SVR performs comparably to nonlinear models and thus can be used in order to facilitate further attempts to design more accurate RSA prediction methods, with applications to fold recognition and de novo protein structure prediction methods.
10541457
Maximum feasibility guideline in the design and analysis of protein folding potentials
Protein folding potentials are expected to have the lowest energy for the native shape. The Linear Programming (LP) approach achieves exactly that goal for a training set, or indicates that this goal is impossible to obtain. If a solution cannot be found (i.e., the problem is infeasible) two possible routes are possible: (a) choosing a new functional form for the potential, (b) finding the best potential with a feasible subset of the data, and (or) detecting inconsistent subset of the data in the training set. Here, we explore option (b). A simple heuristic for finding an approximate solution to an infeasible set of linear inequalities is outlined. An approximately feasible solution is obtained iteratively, starting from a certain initial guess, by computing a series of analytic centers of the polyhedra defined by all the inequalities satisfied at the subsequent iterations. Standard interior point algorithms for Linear Programming can be used to compute efficiently the analytic center of a polyhedron. We demonstrate how this procedure can be used for the design of folding potentials that are linear in their parameters. The procedure shows an improvement in the quality of the potentials and sometimes points to flaws in the original data.
2959784
Computational protein biomarker prediction: a case study for prostate cancer
BackgroundRecent technological advances in mass spectrometry pose challenges in computational mathematics and statistics to process the mass spectral data into predictive models with clinical and biological significance. We discuss several classification-based approaches to finding protein biomarker candidates using protein profiles obtained via mass spectrometry, and we assess their statistical significance. Our overall goal is to implicate peaks that have a high likelihood of being biologically linked to a given disease state, and thus to narrow the search for biomarker candidates.ResultsThorough cross-validation studies and randomization tests are performed on a prostate cancer dataset with over 300 patients, obtained at the Eastern Virginia Medical School using SELDI-TOF mass spectrometry. We obtain average classification accuracies of 87% on a four-group classification problem using a two-stage linear SVM-based procedure and just 13 peaks, with other methods performing comparably.ConclusionsModern feature selection and classification methods are powerful techniques for both the identification of biomarker candidates and the related problem of building predictive models from protein mass spectrometric profiles. Cross-validation and randomization are essential tools that must be performed carefully in order not to bias the results unfairly. However, only a biological validation and identification of the underlying proteins will ultimately confirm the actual value and power of any computational predictions.
32953498
A geostatistical model for linear prediction analysis of speech
Abstract This paper presents a geostatistical model as a new approach to the linear prediction analysis of speech. The autocorrelation method of autoregressive modeling, which is widely applied in the linear predictive coding of speech, is used as a benchmark for comparison with the present algorithm. Before discussing the proposed model, we will briefly describe the concepts of linear prediction analysis of speech and how this is solved by the well-known method of autocorrelation. Following is the introduction of geostatistics including the ideas of regionalized variables, semi-variograms and kriging equations. We then propose a geostatistical model to the linear prediction modeling of speech signals. Examples on speech data are given to illustrate the effectiveness of the present algorithm in comparison with the autocorrelation method. Advantages offered by the proposed geostatistical algorithm over the autocorrelation method in the linear prediction analysis of speech are summarized as follows: (1) it is more effective due to the optimization of the kriging equations taking into account the biased condition; (2) it is more flexible by allowing different biased values for the fitting of the signal spectrum, and therefore may provide a means for adaptive LPC; (3) it can give a good estimate of the number of poles used in the LPC by means of the theoretical semi-variogram.
35465720
Reliability score based multimodal fusion for biometric person authentication
In this paper, we propose a robust multilevel fusion strategy involving cascaded fusion of hybrid multimodal fusion of audio-lip-face motion, correlation and depth features for biometric person authentication. The proposed approach combines the information from different audio-video based modules, namely: audio-lip motion module, audio-lip correlation module, 2D+3D motiondepth fusion module, and performs a hybrid cascaded fusion in an automatic, unsupervised and adaptive manner, by adapting to the local performance of each module. This is done by taking the output-score based reliability estimates (confidence measures) of each of the module into account. The module weightings are determined automatically such that the reliability measure of the combined scores is maximised. To test the robustness of the proposed approach, the audio and visual speech (mouth) modalities are degraded to emulate various levels of train/test mismatch; employing additive white Gaussian noise for the audio and JPEG compression for the video signals. The results show improved fusion performance for a range of tested levels of audio and video degradation, compared to the individual module performances. Experiments on a 3D stereovision database AVOZES show that, at severe levels of audio and video mismatch, the audio, mouth, 3D face, and tri-module (audio-lip motion, correlation and depth) fusion EERs were 42.9%, 32%, 15%, and 7.3% respectively for biometric person authentication task.
14362967
What's Strange About Recent Events (WSARE): An Algorithm for the Early Detection of Disease Outbreaks
Traditional biosurveillance algorithms detect disease outbreaks by looking for peaks in a univariate time series of health-care data. Current health-care surveillance data, however, are no longer simply univariate data streams. Instead, a wealth of spatial, temporal, demographic and symptomatic information is available. We present an early disease outbreak detection algorithm called What's Strange About Recent Events (WSARE), which uses a multivariate approach to improve its timeliness of detection. WSARE employs a rule-based technique that compares recent health-care data against data from a baseline distribution and finds subgroups of the recent data whose proportions have changed the most from the baseline data. In addition, health-care data also pose difficulties for surveillance algorithms because of inherent temporal trends such as seasonal effects and day of week variations. WSARE approaches this problem using a Bayesian network to produce a baseline distribution that accounts for these temporal trends. The algorithm itself incorporates a wide range of ideas, including association rules, Bayesian networks, hypothesis testing and permutation tests to produce a detection algorithm that is careful to evaluate the significance of the alarms that it raises.
34651476
User verification through pointing characteristics: an exploration examination
Abstract Previous research has highlighted that all data security systems rest on the assumption of accurate user verification. Although much research has focused on speech and keystroke characteristics, no study has examined the potential of indirect cursor control devices, such as mouse or pen, as a means of personal user verification. This paper presents the result of an exploratory examination of the measurement of individual users' behaviour elicited while using two indirect input devices (puck and pen). Ten subjects undertook two series of 500 trials using the puck and pen in a counterbalanced design. Each trial involved guiding the cursor to one of ten possible targets, projected upon one of five angles of projection and one of two distances. Data recorded comprised a series of ( x, y) coordinates and associated time stamps of each component of the movement. Five parameters for each full movement were extracted-total time to reach the target, maximum velocity of the movement, maximum acceleration for the movement, time to maximum velocity of movement, time to maximum acceleration of the movement. Results of a series of Multivariate Analyses of Variance indicated that for both the puck and the pen data, there were statistically significant differences between subjects for each of the five parameters. This set of discriminating parameters was then embedded in a verification paradigm. Results indicated that the average error rates varied between 39% (S.D.=2%) and 14% (S.D.=2%) for the puck and 38% (S.D.=2%) and 12% (S.D.=2%) for the pen. Error rates were dependent upon the number of samples used when making the verification decision. This research suggests that pointing device measurements using the current parameters are not a viable method of user verification by themselves. However, with average error rates as low as 12%, it may be reasonable to integrate them into a multi-modal security system. Practical implications and future research directions are discussed.
37589160
A Fuzzy Approach to Speaker Verification
This paper proposes a fuzzy approach to speaker verification. For an input utterance and a claimed identity, most of the current methods compute a claimed speaker's score, which is the ratio of the claimed speaker's and the impostors' likelihood functions, and compare this score with a given threshold to accept or reject this speaker. Considering the speaker verification problem based on fuzzy set theory, the claimed speaker's score is viewed as the fuzzy membership function of the input utterance in the claimed speaker's fuzzy set of utterances. Fuzzy entropy and fuzzy c-means membership functions are proposed as fuzzy membership scores, which are the ratios of functions of the claimed speaker's and impostors' likelihood functions. A likelihood transformation is also considered to relate current likelihood and fuzzy membership scores. We also proposed fuzzy scores using membership functions similar to those produced by noise-clustering-based method. This noise clustering concept provides very effective modifications to several methods, which can overcome some of the problems of ratio-type scores and greatly reduce the false acceptance rate. Experiments were performed to evaluate proposed normalization methods for speaker verification using the YOHO corpus. Experiments demonstrate that fuzzy methods and their noise clustering versions outperform conventional methods.