PCSF: An R-package for network-based interpretation of high-throughput data

With the recent technological developments a vast amount of high-throughput data has been profiled to understand the mechanism of complex diseases. The current bioinformatics challenge is to interpret the data and underlying biology, where efficient algorithms for analyzing heterogeneous high-throughput data using biological networks are becoming increasingly valuable. In this paper, we propose a software package based on the Prize-collecting Steiner Forest graph optimization approach. The PCSF package performs fast and user-friendly network analysis of high-throughput data by mapping the data onto a biological networks such as protein-protein interaction, gene-gene interaction or any other correlation or coexpression based networks. Using the interaction networks as a template, it determines high-confidence subnetworks relevant to the data, which potentially leads to predictions of functional units. It also interactively visualizes the resulting subnetwork with functional enrichment analysis

Combinatorial structures to modeling simple games and applications

We connect three different topics: combinatorial structures, game theory and chemistry. In particular, we establish the bases to represent some simple games, defined as influence games, and molecules, defined from atoms, by using combinatorial structures. First, we characterize simple games as influence games using influence graphs. It let us to modeling simple games as combinatorial structures (from the viewpoint of structures or graphs). Second, we formally define molecules as combinations of atoms. It let us to modeling molecules as combinatorial structures (from the viewpoint of combinations). It is open to generate such combinatorial structures using some specific techniques as genetic algorithms, (meta-)heuristics algorithms and parallel programming, among others.Peer ReviewedPostprint (published version

Identification of phenotype-specific networks from paired gene expression-cell shape imaging data

The morphology of breast cancer cells is often used as an indicator of tumor severity and prognosis. Additionally, morphology can be used to identify more fine-grained, molecular developments within a cancer cell, such as transcriptomic changes and signaling pathway activity. Delineating the interface between morphology and signaling is important to understand the mechanical cues that a cell processes in order to undergo epithelial-to-mesenchymal transition and consequently metastasize. However, the exact regulatory systems that define these changes remain poorly characterized. In this study, we used a network-systems approach to integrate imaging data and RNA-seq expression data. Our workflow allowed the discovery of unbiased and context-specific gene expression signatures and cell signaling subnetworks relevant to the regulation of cell shape, rather than focusing on the identification of previously known, but not always representative, pathways. By constructing a cell-shape signaling network from shape-correlated gene expression modules and their upstream regulators, we found central roles for developmental pathways such as WNT and Notch, as well as evidence for the fine control of NF-kB signaling by numerous kinase and transcriptional regulators. Further analysis of our network implicates a gene expression module enriched in the RAP1 signaling pathway as a mediator between the sensing of mechanical stimuli and regulation of NF-kB activity, with specific relevance to cell shape in breast cancer

Operational Research: Methods and Applications

Throughout its history, Operational Research has evolved to include a variety of methods, models and algorithms that have been applied to a diverse and wide range of contexts. This encyclopedic article consists of two main sections: methods and applications. The first aims to summarise the up-to-date knowledge and provide an overview of the state-of-the-art methods and key developments in the various subdomains of the field. The second offers a wide-ranging list of areas where Operational Research has been applied. The article is meant to be read in a nonlinear fashion. It should be used as a point of reference or first-port-of-call for a diverse pool of readers: academics, researchers, students, and practitioners. The entries within the methods and applications sections are presented in alphabetical order. The authors dedicate this paper to the 2023 Turkey/Syria earthquake victims. We sincerely hope that advances in OR will play a role towards minimising the pain and suffering caused by this and future catastrophes

Operational research:methods and applications

Throughout its history, Operational Research has evolved to include a variety of methods, models and algorithms that have been applied to a diverse and wide range of contexts. This encyclopedic article consists of two main sections: methods and applications. The first aims to summarise the up-to-date knowledge and provide an overview of the state-of-the-art methods and key developments in the various subdomains of the field. The second offers a wide-ranging list of areas where Operational Research has been applied. The article is meant to be read in a nonlinear fashion. It should be used as a point of reference or first-port-of-call for a diverse pool of readers: academics, researchers, students, and practitioners. The entries within the methods and applications sections are presented in alphabetical order

New variants of variable neighbourhood search for 0-1 mixed integer programming and clustering

Many real-world optimisation problems are discrete in nature. Although recent rapid developments in computer technologies are steadily increasing the speed of computations, the size of an instance of a hard discrete optimisation problem solvable in prescribed time does not increase linearly with the computer speed. This calls for the development of new solution methodologies for solving larger instances in shorter time. Furthermore, large instances of discrete optimisation problems are normally impossible to solve to optimality within a reasonable computational time/space and can only be tackled with a heuristic approach. In this thesis the development of so called matheuristics, the heuristics which are based on the mathematical formulation of the problem, is studied and employed within the variable neighbourhood search framework. Some new variants of the variable neighbourhood searchmetaheuristic itself are suggested, which naturally emerge from exploiting the information from the mathematical programming formulation of the problem. However, those variants may also be applied to problems described by the combinatorial formulation. A unifying perspective on modern advances in local search-based metaheuristics, a so called hyper-reactive approach, is also proposed. Two NP-hard discrete optimisation problems are considered: 0-1 mixed integer programming and clustering with application to colour image quantisation. Several new heuristics for 0-1 mixed integer programming problem are developed, based on the principle of variable neighbourhood search. One set of proposed heuristics consists of improvement heuristics, which attempt to find high-quality near-optimal solutions starting from a given feasible solution. Another set consists of constructive heuristics, which attempt to find initial feasible solutions for 0-1 mixed integer programs. Finally, some variable neighbourhood search based clustering techniques are applied for solving the colour image quantisation problem. All new methods presented are compared to other algorithms recommended in literature and a comprehensive performance analysis is provided. Computational results show that the methods proposed either outperform the existing state-of-the-art methods for the problems observed, or provide comparable results. The theory and algorithms presented in this thesis indicate that hybridisation of the CPLEX MIP solver and the VNS metaheuristic can be very effective for solving large instances of the 0-1 mixed integer programming problem. More generally, the results presented in this thesis suggest that hybridisation of exact (commercial) integer programming solvers and some metaheuristic methods is of high interest and such combinations deserve further practical and theoretical investigation. Results also show that VNS can be successfully applied to solving a colour image quantisation problem.EThOS - Electronic Theses Online ServiceMathematical Institute, Serbian Academy of Sciences and ArtsGBUnited Kingdo

A divide and conquer matheuristic algorithm for the Prize-collecting Steiner Tree Problem

The Prize-collecting Steiner Tree Problem (PCSTP) is a well-known problem in graph theory and combinatorial optimization. It has been successfully applied to solve real problems such as fiber-optic and gas distribution networks design. In this work, we concentrate on its application in biology to perform a functional analysis of genes. It is common to analyze large networks in genomics to infer a hidden knowledge. Due to the NP-hard characteristics of the PCSTP, it is computationally costly, if possible, to achieve exact solutions for such huge instances. Therefore, there is a need for fast and efficient matheuristic algorithms to explore and understand the concealed information in huge biological graphs. In this study, we propose a matheuristic method based on clustering algorithm. The main target of the method is to scale up the applicability of the currently available exact methods to large graph instances, without loosing too much on solution quality. The proposed matheuristic method is composed of a preprocessing procedures, a heuristic clustering algorithm and an exact solver for the PCSTP, applied on sub-graphs. We examine the performance of the proposed method on real-world benchmark instances from biology, and compare its results with those of the exact solver alone, without the heuristic clustering. We obtain solutions in shorter execution time and with negligible optimality gaps. This enables analyzing very large biological networks with the currently available exact solvers