10411388
Large-scale linear programming techniques for the design of protein folding potentials
Abstract.We present large-scale optimization techniques to model the energy function that underlies the folding process of proteins. Linear Programming is used to identify parameters in the energy function model, the objective being that the model predict the structure of known proteins correctly. Such trained functions can then be used either for ab-initio prediction or for recognition of unknown structures. In order to obtain good energy models we need to be able to solve dense Linear Programming Problems with tens (possibly hundreds) of millions of constraints in a few hundred parameters, which we achieve by tailoring and parallelizing the interior-point code PCx.
18133525
pPCx: Parallel Software for Linear Programming
We describe pPCx, a parallel variant of the PCx interior-point code for linear programming. We outline the major computational operation|parallel multifrontal Cholesky factorization|and present computational results on the IBM-SP multipro-cessor.
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.
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.
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.
7724289
Outpatient clinic scheduling - a simulation approach
The process by which outpatients are scheduled for a doctor's visit is a crucial determinant of the overall efficiency of the patient flow. The problem at hand consists of determining prioritization (triage) rules so that adequate patient care is guaranteed, resources (provider schedules) are utilized efficiently and a service guarantee can be ensured. We present a simulation framework for the evaluation and optimization of scheduling rules. We outline the basic ingredients of our model, illustrate the kinds of analyses it has enabled us to perform and summarize our experience with a preliminary implementation for the Division of Pediatric Ophthalmology at Cincinnati Children's Hospital Medical Center. Challenges for adaptations to other settings are also outlined.
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.
13891540
MagicMeeting: A Collaborative Tangible Augmented Reality System
We describe an augmented reality (AR) system that allows multiple participants to interact with 2D and 3D data using tangible user interfaces. The system features face-to-face communication, collaborative viewing and manipulation of 3D models, and seamless access to 2D desktop applications within the shared 3D space. All virtual content, including 3D models and 2D desktop windows, is attached to tracked physical objects in order to leverage the efficiencies of natural two-handed manipulation. The presence of 2D desktop space within 3D facilitates data exchange between the two realms, enables control of 3D information by 2D applications, and generally increases productivity by providing access to familiar tools. We present a general concept for a collaborative tangible AR system, including a comprehensive set of interaction techniques, a distributed hardware setup, and a component-based software architecture that can be flexibly configured using XML. We show the validity of our concept with an implementation of an application scenario from the automotive industry.
16477809
EventScope: Bringing Remote Experience of Mars to the Public through Telepresence
Telepresence, experiencing a place without physically being there, offers an important means for the public experience of remote locations such as distant continents or other planets. EventScope presents one such telepresence visualization interface for bringing scientific missions to the public. Currently, remote experience lessons based on NASA’s Mars Exploration Rover missions are being made available through the EventScope framework to museums, classrooms, and the public at large.
751960
Performance Evaluation Methodologies for Abstract Data Type Implementation Techniques
Abstract The runtime management system for a programming language must allow the efficient manipulation of complex objects, such as instances of abstract data types (ADTs). We describe an implementation model for ADTs based on coroutine objects (i.e. as an alternative to ad hoc modifications of the runtime stack). We evaluate the performances of variants of our implementation model using two different approaches: a benchmarking technique which monitors actual costs for test programs and a “pseudo-execution” technique which estimates costs based on idealized instruction timings. The results of our comparison indicate that the two forms of evaluation give very similar cost estimates, supporting the use of the (cheaper) pseudo-execution technique. The overall performance results identify applications in which our coroutine implementation model has definite strengths and weaknesses. Finally, our implementation approach is compared with modified stack implementations used in other ADT systems.
14005418
A Comprehensive Context Modeling Framework for Pervasive Computing Systems
Context management in pervasive computing environments must reflect the specific characteristics of these environments, e.g. distribution, mobility, resource-constrained devices, or heterogeneity of context sources. Although a number of context models have been presented in the literature, none of them supports all of these requirements to a sufficient extent at the same time. In this paper, we present a comprehensive and integrated approach for context modeling in pervasive computing environments. It combines the advantages of existing approaches and addresses the need for supporting effective software development. The proposed context model follows an ontology-based approach and has three layers of abstraction, i.e. conceptual layer, exchange layer, and functional layer. This layered approach facilitates a model-driven development of context-aware applications. Throughout the paper we compare our solution with the related work in order to clearly demonstrate why we needed to develop a new context management framework and where we have adopted existing ideas.