Algorithm engineering for optimal alignment of protein structure distance matrices

Protein structural alignment is an important problem in computational biology. In this paper, we present first successes on provably optimal pairwise alignment of protein inter-residue distance matrices, using the popular Dali scoring function. We introduce the structural alignment problem formally, which enables us to express a variety of scoring functions used in previous work as special cases in a unified framework. Further, we propose the first mathematical model for computing optimal structural alignments based on dense inter-residue distance matrices. We therefore reformulate the problem as a special graph problem and give a tight integer linear programming model. We then present algorithm engineering techniques to handle the huge integer linear programs of real-life distance matrix alignment problems. Applying these techniques, we can compute provably optimal Dali alignments for the very first time

CMView: Interactive contact map visualization and analysis

Summary: Contact maps are a valuable visualization tool in structural biology. They are a convenient way to display proteins in two dimensions and to quickly identify structural features such as domain architecture, secondary structure and contact clusters. We developed a tool called CMView which integrates rich contact map analysis with 3D visualization using PyMol. Our tool provides functions for contact map calculation from structure, basic editing, visualization in contact map and 3D space and structural comparison with different built-in alignment methods. A unique feature is the interactive refinement of structural alignments based on user selected substructures. Availability: CMView is freely available for Linux, Windows and MacOS. The software and a comprehensive manual can be downloaded from http://www.bioinformatics.org/cmview/. The source code is licensed under the GNU General Public License. Contact: [email protected], [email protected]

Comparing Protein 3D Structures Using A_purva

Structural similarity between proteins provides significant insights about their functions. Maximum Contact Map Overlap maximization (CMO) received sustained attention during the past decade and can be considered today as a credible protein structure measure. We present here A_purva, an exact CMO solver that is both efficient (notably faster than the previous exact algorithms), and reliable (providing accurate upper and lower bounds of the solution). These properties make it applicable for large-scale protein comparison and classification. Availability: http://apurva.genouest.org Contact: [email protected] Supplementary information: A_purva's user manual, as well as many examples of protein contact maps can be found on A_purva's web-page.La similarité structurale entre protéines donne des renseignements importants sur leurs fonctions. La maximisation du recouvrement de cartes de contacts (CMO) a reçu une attention soutenue ces dix dernières années, et est maintenant considérée comme une mesure de similarité crédible. Nous présentons içi A_purva, un solveur de CMO exacte qui est à la fois efficace (plus rapide que les autres algorithmes exactes) et fiable (fournit des bornes supérieures et inférieures précises de la solution). Ces propriétés le rendent applicable pour des comparaisons et des classifications de protéines à grandes échelles. Disponibilité : http://apurva.genouest.org Contact : [email protected] Informations supplémentaires : Le manuel utilisateur d'A_purva, ainsi que de nombreux exemples de cartes de contacts de protéines sont disponibles sur le site web d'A_purva

Exact algorithms for pairwise protein structure alignment

Klau, G.W. [Promotor

Multi-Modal Partial Surface Matching for Intra-Operative Registration

An important task for computer-assisted surgical interventions is the alignment of pre- and intra-operative spaces allowing the transfer of pre-operative information to the current patient situation, known as intra-operative registration. Registration is usually performed by using markers or image-based techniques. Another approach is the intra-operative acquisition of organ surfaces by 3D range scanners, which are then matched to pre-operatively generated surfaces. However, this approach is not trivial, as methods for intra-operative surface matching must be able to deal with noise, distortions, deformations, and the availability of only partially overlapping, nearly flat surfaces. For these reasons, surface matching for intra-operative registration has so far only been used to account for displacements that occur in local scales, while the actual alignment is still performed manually. The main contributions of this thesis are two different approaches for automatic surface matching in intra-operative environments. The focus here is the registration of surfaces acquired by different modalities, dealing with the aforementioned issues and without relying on unique landmarks. For the first approach, surfaces are converted to graph representations and correspondences between them are identified by means of graph matching. Graphs are obtained automatically by segmenting the surfaces into regions with similar properties. As the graph matching problem is known to be NP-hard, it was solved by iteratively computing node similarity scores, and converting it to a linear assignment problem. In the second approach, correspondences are identified by the selection of two spatial configurations of landmarks that can be better fitted to each other, according to an error metric. This error metric does not only incorporate a fitting error, but also a new measure for spatial configuration reliability. The optimization problem is solved by means of a greedy algorithm. Evaluation of the two approaches was performed with several experiments, simulating intra-operative conditions. While the graph matching approach proved to be robust for the registration of small partial data, the point-based approach proved to be more reliable for noisy surfaces. Apart from being a significant contribution to the field of feature-less partial surface matching, this work represents a great effort towards the achievement of a fully automatic, marker-less, registration system for computer-assisted surgery guidance

Shape Dynamical Models for Activity Recognition and Coded Aperture Imaging for Light-Field Capture

Classical applications of Pattern recognition in image processing and computer vision have typically dealt with modeling, learning and recognizing static patterns in images and videos. There are, of course, in nature, a whole class of patterns that dynamically evolve over time. Human activities, behaviors of insects and animals, facial expression changes, lip reading, genetic expression profiles are some examples of patterns that are dynamic. Models and algorithms to study these patterns must take into account the dynamics of these patterns while exploiting the classical pattern recognition techniques. The first part of this dissertation is an attempt to model and recognize such dynamically evolving patterns. We will look at specific instances of such dynamic patterns like human activities, and behaviors of insects and develop algorithms to learn models of such patterns and classify such patterns. The models and algorithms proposed are validated by extensive experiments on gait-based person identification, activity recognition and simultaneous tracking and behavior analysis of insects. The problem of comparing dynamically deforming shape sequences arises repeatedly in problems like activity recognition and lip reading. We describe and evaluate parametric and non-parametric models for shape sequences. In particular, we emphasize the need to model activity execution rate variations and propose a non-parametric model that is insensitive to such variations. These models and the resulting algorithms are shown to be extremely effective for a wide range of applications from gait-based person identification to human action recognition. We further show that the shape dynamical models are not only effective for the problem of recognition, but also can be used as effective priors for the problem of simultaneous tracking and behavior analysis. We validate the proposed algorithm for performing simultaneous behavior analysis and tracking on videos of bees dancing in a hive. In the last part of this dissertaion, we investigate computational imaging, an emerging field where the process of image formation involves the use of a computer. The current trend in computational imaging is to capture as much information about the scene as possible during capture time so that appropriate images with varying focus, aperture, blur and colorimetric settings may be rendered as required. In this regard, capturing the 4D light-field as opposed to a 2D image allows us to freely vary viewpoint and focus at the time of rendering an image. In this dissertation, we describe a theoretical framework for reversibly modulating {4D} light fields using an attenuating mask in the optical path of a lens based camera. Based on this framework, we present a novel design to reconstruct the {4D} light field from a {2D} camera image without any additional refractive elements as required by previous light field cameras. The patterned mask attenuates light rays inside the camera instead of bending them, and the attenuation recoverably encodes the rays on the {2D} sensor. Our mask-equipped camera focuses just as a traditional camera to capture conventional {2D} photos at full sensor resolution, but the raw pixel values also hold a modulated {4D} light field. The light field can be recovered by rearranging the tiles of the {2D} Fourier transform of sensor values into {4D} planes, and computing the inverse Fourier transform. In addition, one can also recover the full resolution image information for the in-focus parts of the scene

Joining softassign and dynamic programming for the contact map overlap problem

Comparison of 3-dimensional protein folds is a core problem in molecular biology. The Contact Map Overlap (CMO) scheme provides one of the most common measures for protein structure similarity. Maximizing CMO is, however, NP-hard. To approximately solve CMO, we combine softassign and dynamic programming. Softassign approximately solves the maximum common subgraph (MCS) problem. Dynamic programming converts the MCS solution to a solution of the CMO problem. We present and discuss experiments using proteins with up to 1500 residues. The results indicate that the proposed method is extremely fast compared to other methods, scales well with increasing problem size, and is useful for comparing similar protein structures

In Silico Strategies for Prospective Drug Repositionings

The discovery of new drugs is one of pharmaceutical research's most exciting and challenging tasks. Unfortunately, the conventional drug discovery procedure is chronophagous and seldom successful; furthermore, new drugs are needed to address our clinical challenges (e.g., new antibiotics, new anticancer drugs, new antivirals).Within this framework, drug repositioning—finding new pharmacodynamic properties for already approved drugs—becomes a worthy drug discovery strategy.Recent drug discovery techniques combine traditional tools with in silico strategies to identify previously unaccounted properties for drugs already in use. Indeed, big data exploration techniques capitalize on the ever-growing knowledge of drugs' structural and physicochemical properties, drug–target and drug–drug interactions, advances in human biochemistry, and the latest molecular and cellular biology discoveries.Following this new and exciting trend, this book is a collection of papers introducing innovative computational methods to identify potential candidates for drug repositioning. Thus, the papers in the Special Issue In Silico Strategies for Prospective Drug Repositionings introduce a wide array of in silico strategies such as complex network analysis, big data, machine learning, molecular docking, molecular dynamics simulation, and QSAR; these strategies target diverse diseases and medical conditions: COVID-19 and post-COVID-19 pulmonary fibrosis, non-small lung cancer, multiple sclerosis, toxoplasmosis, psychiatric disorders, or skin conditions