A topological approach for protein classification

Protein function and dynamics are closely related to its sequence and structure. However prediction of protein function and dynamics from its sequence and structure is still a fundamental challenge in molecular biology. Protein classification, which is typically done through measuring the similarity be- tween proteins based on protein sequence or physical information, serves as a crucial step toward the understanding of protein function and dynamics. Persistent homology is a new branch of algebraic topology that has found its success in the topological data analysis in a variety of disciplines, including molecular biology. The present work explores the potential of using persistent homology as an indepen- dent tool for protein classification. To this end, we propose a molecular topological fingerprint based support vector machine (MTF-SVM) classifier. Specifically, we construct machine learning feature vectors solely from protein topological fingerprints, which are topological invariants generated during the filtration process. To validate the present MTF-SVM approach, we consider four types of problems. First, we study protein-drug binding by using the M2 channel protein of influenza A virus. We achieve 96% accuracy in discriminating drug bound and unbound M2 channels. Additionally, we examine the use of MTF-SVM for the classification of hemoglobin molecules in their relaxed and taut forms and obtain about 80% accuracy. The identification of all alpha, all beta, and alpha-beta protein domains is carried out in our next study using 900 proteins. We have found a 85% success in this identifica- tion. Finally, we apply the present technique to 55 classification tasks of protein superfamilies over 1357 samples. An average accuracy of 82% is attained. The present study establishes computational topology as an independent and effective alternative for protein classification

Spatial Aggregation: Theory and Applications

Visual thinking plays an important role in scientific reasoning. Based on the research in automating diverse reasoning tasks about dynamical systems, nonlinear controllers, kinematic mechanisms, and fluid motion, we have identified a style of visual thinking, imagistic reasoning. Imagistic reasoning organizes computations around image-like, analogue representations so that perceptual and symbolic operations can be brought to bear to infer structure and behavior. Programs incorporating imagistic reasoning have been shown to perform at an expert level in domains that defy current analytic or numerical methods. We have developed a computational paradigm, spatial aggregation, to unify the description of a class of imagistic problem solvers. A program written in this paradigm has the following properties. It takes a continuous field and optional objective functions as input, and produces high-level descriptions of structure, behavior, or control actions. It computes a multi-layer of intermediate representations, called spatial aggregates, by forming equivalence classes and adjacency relations. It employs a small set of generic operators such as aggregation, classification, and localization to perform bidirectional mapping between the information-rich field and successively more abstract spatial aggregates. It uses a data structure, the neighborhood graph, as a common interface to modularize computations. To illustrate our theory, we describe the computational structure of three implemented problem solvers -- KAM, MAPS, and HIPAIR --- in terms of the spatial aggregation generic operators by mixing and matching a library of commonly used routines.Comment: See http://www.jair.org/ for any accompanying file

The Energy Landscape, Folding Pathways and the Kinetics of a Knotted Protein

The folding pathway and rate coefficients of the folding of a knotted protein are calculated for a potential energy function with minimal energetic frustration. A kinetic transition network is constructed using the discrete path sampling approach, and the resulting potential energy surface is visualized by constructing disconnectivity graphs. Owing to topological constraints, the low-lying portion of the landscape consists of three distinct regions, corresponding to the native knotted state and to configurations where either the N- or C-terminus is not yet folded into the knot. The fastest folding pathways from denatured states exhibit early formation of the N-terminus portion of the knot and a rate-determining step where the C-terminus is incorporated. The low-lying minima with the N-terminus knotted and the C-terminus free therefore constitute an off-pathway intermediate for this model. The insertion of both the N- and C-termini into the knot occur late in the folding process, creating large energy barriers that are the rate limiting steps in the folding process. When compared to other protein folding proteins of a similar length, this system folds over six orders of magnitude more slowly.Comment: 19 page

Image database system for glaucoma diagnosis support

Tato práce popisuje přehled standardních a pokročilých metod používaných k diagnose glaukomu v ranném stádiu. Na základě teoretických poznatků je implementován internetově orientovaný informační systém pro oční lékaře, který má tři hlavní cíle. Prvním cílem je možnost sdílení osobních dat konkrétního pacienta bez nutnosti posílat tato data internetem. Druhým cílem je vytvořit účet pacienta založený na kompletním očním vyšetření. Posledním cílem je aplikovat algoritmus pro registraci intenzitního a barevného fundus obrazu a na jeho základě vytvořit internetově orientovanou tři-dimenzionální vizualizaci optického disku. Tato práce je součásti DAAD spolupráce mezi Ústavem Biomedicínského Inženýrství, Vysokého Učení Technického v Brně, Oční klinikou v Erlangenu a Ústavem Informačních Technologií, Friedrich-Alexander University, Erlangen-Nurnberg.This master thesis describes a conception of standard and advanced eye examination methods used for glaucoma diagnosis in its early stage. According to the theoretical knowledge, a web based information system for ophthalmologists with three main aims is implemented. The first aim is the possibility to share medical data of a concrete patient without sending his personal data through the Internet. The second aim is to create a patient account based on a complete eye examination procedure. The last aim is to improve the HRT diagnostic method with an image registration algorithm for the fundus and intensity images and create an optic nerve head web based 3D visualization. This master thesis is a part of project based on DAAD co-operation between Department of Biomedical Engineering, Brno University of Technology, Eye Clinic in Erlangen and Department of Computer Science, Friedrich-Alexander University, Erlangen-Nurnberg.