ProtNN: Fast and Accurate Nearest Neighbor Protein Function Prediction based on Graph Embedding in Structural and Topological Space

Studying the function of proteins is important for understanding the molecular mechanisms of life. The number of publicly available protein structures has increasingly become extremely large. Still, the determination of the function of a protein structure remains a difficult, costly, and time consuming task. The difficulties are often due to the essential role of spatial and topological structures in the determination of protein functions in living cells. In this paper, we propose ProtNN, a novel approach for protein function prediction. Given an unannotated protein structure and a set of annotated proteins, ProtNN finds the nearest neighbor annotated structures based on protein-graph pairwise similarities. Given a query protein, ProtNN finds the nearest neighbor reference proteins based on a graph representation model and a pairwise similarity between vector embedding of both query and reference protein-graphs in structural and topological spaces. ProtNN assigns to the query protein the function with the highest number of votes across the set of k nearest neighbor reference proteins, where k is a user-defined parameter. Experimental evaluation demonstrates that ProtNN is able to accurately classify several datasets in an extremely fast runtime compared to state-of-the-art approaches. We further show that ProtNN is able to scale up to a whole PDB dataset in a single-process mode with no parallelization, with a gain of thousands order of magnitude of runtime compared to state-of-the-art approaches

Mining Representative Unsubstituted Graph Patterns Using Prior Similarity Matrix

One of the most powerful techniques to study protein structures is to look for recurrent fragments (also called substructures or spatial motifs), then use them as patterns to characterize the proteins under study. An emergent trend consists in parsing proteins three-dimensional (3D) structures into graphs of amino acids. Hence, the search of recurrent spatial motifs is formulated as a process of frequent subgraph discovery where each subgraph represents a spatial motif. In this scope, several efficient approaches for frequent subgraph discovery have been proposed in the literature. However, the set of discovered frequent subgraphs is too large to be efficiently analyzed and explored in any further process. In this paper, we propose a novel pattern selection approach that shrinks the large number of discovered frequent subgraphs by selecting the representative ones. Existing pattern selection approaches do not exploit the domain knowledge. Yet, in our approach we incorporate the evolutionary information of amino acids defined in the substitution matrices in order to select the representative subgraphs. We show the effectiveness of our approach on a number of real datasets. The results issued from our experiments show that our approach is able to considerably decrease the number of motifs while enhancing their interestingness

Towards an Efficient Discovery of the Topological Representative Subgraphs

With the emergence of graph databases, the task of frequent subgraph discovery has been extensively addressed. Although the proposed approaches in the literature have made this task feasible, the number of discovered frequent subgraphs is still very high to be efficiently used in any further exploration. Feature selection for graph data is a way to reduce the high number of frequent subgraphs based on exact or approximate structural similarity. However, current structural similarity strategies are not efficient enough in many real-world applications, besides, the combinatorial nature of graphs makes it computationally very costly. In order to select a smaller yet structurally irredundant set of subgraphs, we propose a novel approach that mines the top-k topological representative subgraphs among the frequent ones. Our approach allows detecting hidden structural similarities that existing approaches are unable to detect such as the density or the diameter of the subgraph. In addition, it can be easily extended using any user defined structural or topological attributes depending on the sought properties. Empirical studies on real and synthetic graph datasets show that our approach is fast and scalable

Towards an Efficient Discovery of Topological Representative Subgraphs

National audienceLa sélection de motifs basée sur la similarité structurelle exacte ou approximative est un moyen de réduire le nombre élevé des sous-graphes fréquents. Cependant, les stratégies actuelles de similarité structurelle ne sont pas efficaces dans beaucoup de contextes réels. En outre, la nature combinatoire des graphes rend l'isomorphisme exact ou approximatif très coûteux. Dans ce papier, nous proposons une approche qui permet de sélectionner un sous-ensemble de sous-graphes topologiques représentatifs parmi les fréquents. L'approche proposée surmonte le coûteux test d'isomorphisme exact ou approximatif en mesurant la similarité structurelle globale en se basant sur un ensemble d'attributs topologiques considérés. Elle permet aussi de détecter des similaritées structurelles cachées (tels que la densité, le diamètre, etc.) qui ne sont pas considérées par les approches existantes. En outre, l'approche proposée est flexible et peut être facilement étendue avec des attributs définis par l'utilisateur selon l'application. Les analyses expérimentales sur des bases de graphes réelles et synthétiques montrent l'efficacité de notre approche

Discovery of Functional Motifs from the Interface Region of Oligomeric Proteins using Frequent Subgraph Mining

Modeling the interface region of a protein complex paves the way for understanding its dynamics and functionalities. Existing works model the interface region of a complex by using different approaches, such as, the residue composition at the interface region, the geometry of the interface residues, or the structural alignment of interface regions. These approaches are useful for ranking a set of docked conformation or for building scoring function for protein-protein docking, but they do not provide a generic and scalable technique for the extraction of interface patterns leading to functional motif discovery. In this work, we model the interface region of a protein complex by graphs and extract interface patterns of the given complex in the form of frequent subgraphs. To achieve this we develop a scalable algorithm for frequent subgraph mining. We show that a systematic review of the mined subgraphs provides an effective method for the discovery of functional motifs that exist along the interface region of a given protein complex

From SIR to SEAIRD: a novel data-driven modeling approach based on the Grey-box System Theory to predict the dynamics of COVID-19

Common compartmental modeling for COVID-19 is based on a priori knowledge and numerous assumptions. Additionally, they do not systematically incorporate asymptomatic cases. Our study aimed at providing a framework for data-driven approaches, by leveraging the strengths of the grey-box system theory or grey-box identification, known for its robustness in problem solving under partial, incomplete, or uncertain data. Empirical data on confirmed cases and deaths, extracted from an open source repository were used to develop the SEAIRD compartment model. Adjustments were made to fit current knowledge on the COVID-19 behavior. The model was implemented and solved using an Ordinary Differential Equation solver and an optimization tool. A cross-validation technique was applied, and the coefficient of determination $R^2$ was computed in order to evaluate the goodness-of-fit of the model. %to the data. Key epidemiological parameters were finally estimated and we provided the rationale for the construction of SEAIRD model. When applied to Brazil's cases, SEAIRD produced an excellent agreement to the data, with an %coefficient of determination $R^2$ $\geq 90\%$. The probability of COVID-19 transmission was generally high ($\geq 95\%$). On the basis of a 20-day modeling data, the incidence rate of COVID-19 was as low as 3 infected cases per 100,000 exposed persons in Brazil and France. Within the same time frame, the fatality rate of COVID-19 was the highest in France (16.4\%) followed by Brazil (6.9\%), and the lowest in Russia ($\leq 1\%$). SEAIRD represents an asset for modeling infectious diseases in their dynamical stable phase, especially for new viruses when pathophysiology knowledge is very limited

Fouille de sous-graphes basée sur la topologie et la connaissance du domaine : application sur les structures 3D de protéines

This thesis is in the intersection of two proliferating research fields, namely data mining and bioinformatics. With the emergence of graph data in the last few years, many efforts have been devoted to mining frequent subgraphs from graph databases. Yet, the number of discovered frequentsubgraphs is usually exponential, mainly because of the combinatorial nature of graphs. Many frequent subgraphs are irrelevant because they are redundant or just useless for the user. Besides, their high number may hinder and even makes further explorations unfeasible. Redundancy in frequent subgraphs is mainly caused by structural and/or semantic similarities, since most discovered subgraphs differ slightly in structure and may infer similar or even identical meanings. In this thesis, we propose two approaches for selecting representative subgraphs among frequent ones in order to remove redundancy. Each of the proposed approaches addresses a specific type of redundancy. The first approach focuses on semantic redundancy where similarity between subgraphs is measured based on the similarity between their nodes' labels, using prior domain knowledge. The second approach focuses on structural redundancy where subgraphs are represented by a set of user-defined topological descriptors, and similarity between subgraphs is measured based on the distance between their corresponding topological descriptions. The main application data of this thesis are protein 3D-structures. This choice is based on biological and computational reasons. From a biological perspective, proteins play crucial roles in almost every biological process. They are responsible of a variety of physiological functions. From a computational perspective, we are interested in mining complex data. Proteins are a perfect example of such data as they are made of complex structures composed of interconnected amino acids which themselves are composed of interconnected atoms. Large amounts of protein structures are currently available in online databases, in computer analyzable formats. Protein 3D-structures can be transformed into graphs where amino acids are the graph nodes and their connections are the graph edges. This enables using graph mining techniques to study them. The biological importance of proteins, their complexity, and their availability in computer analyzable formats made them a perfect application data for this thesis.Cette thèse est à l'intersection de deux domaines de recherche en plein expansion, à savoir la fouille de données et la bioinformatique. Avec l'émergence des bases de graphes au cours des dernières années, de nombreux efforts ont été consacrés à la fouille des sous-graphes fréquents. Mais le nombre de sous-graphes fréquents découverts est exponentiel, cela est dû principalement à la nature combinatoire des graphes. Beaucoup de sous-graphes fréquents ne sont pas pertinents parce qu'ils sont redondants ou tout simplement inutiles pour l'utilisateur. En outre, leur nombre élevé peut nuire ou même rendre parfois irréalisable toute utilisation ultérieure. La redondance dans les sous-graphes fréquents est principalement due à la similarité structurelle et / ou sémantique, puisque la plupart des sous-graphes découverts diffèrent légèrement dans leur structures et peuvent exprimer des significations similaires ou même identiques. Dans cette thèse, nous proposons deux approches de sélection des sous-graphes représentatifs parmi les fréquents afin d'éliminer la redondance. Chacune des approches proposées s'intéresse à un type spécifique de redondance. La première approche s'adresse à la redondance sémantique où la similarité entre les sous-graphes est mesurée en fonction de la similarité entre les étiquettes de leurs noeuds, en utilisant les connaissances de domaine. La deuxième approche s'adresse à la redondance structurelle où les sous-graphes sont représentés par des descripteurs topologiques définis par l'utilisateur, et la similarité entre les sous-graphes est mesurée en fonction de la distance entre leurs descriptions topologiques respectives. Les principales données d'application de cette thèse sont les structures 3D des protéines. Ce choix repose sur des raisons biologiques et informatiques. D'un point de vue biologique, les protéines jouent un rôle crucial dans presque tous les processus biologiques. Ils sont responsables d'une variété de fonctions physiologiques. D'un point de vue informatique, nous nous sommes intéressés à la fouille de données complexes. Les protéines sont un exemple parfait de ces données car elles sont faites de structures complexes composées d'acides aminés interconnectés qui sont eux-mêmes composées d'atomes interconnectés. Des grandes quantités de structures protéiques sont actuellement disponibles dans les bases de données en ligne. Les structures 3D des protéines peuvent être transformées en graphes où les acides aminés représentent les noeuds du graphe et leurs connexions représentent les arêtes. Cela permet d'utiliser des techniques de fouille de graphes pour les étudier. L'importance biologique des protéines et leur complexité ont fait d'elles des données d'application appropriées pour cette thèse

Face Recognition in the Wild

AbstractFace recognition is one of the most important tasks in pattern recognition and computer vision. The most conventional way to per- form face recognition is to compare a set of facial features that are extracted from a source image or a video frame with a reference image database of known faces. Such a classification takes the form of a prediction within a closed-set of classes. However, a more realistic scenario that fits the ground truth of real-world face recognition applications is to consider the possibility of encountering faces that do not belong to any of the training classes, i.e., an open-set classification. Such a constraint is very challenging to most existing face recognition systems since the latter are based on closed-set classification methods which always assign a training label to novel unknown instances even if they represent unseen faces that are not represented in the reference database. This results in a misclassification. In this paper, we introduce Face Recognition in the Wild (FRW), a novel face recognition system that allows (1) to efficiently recognize known faces from the reference database, and (2) to prevent misclassifying instances that represent unknown and unseen faces. FRW formulates this problem as a multi-class classification in an open-set context where the presence of instances from unknown classes is possible. Experimental results on the challenging Olivetti Faces benchmark dataset show the efficiency of our approach in open-set face recognition problems