The cavity approach for Steiner trees packing problems

The Belief Propagation approximation, or cavity method, has been recently applied to several combinatorial optimization problems in its zero-temperature implementation, the max-sum algorithm. In particular, recent developments to solve the edge-disjoint paths problem and the prize-collecting Steiner tree problem on graphs have shown remarkable results for several classes of graphs and for benchmark instances. Here we propose a generalization of these techniques for two variants of the Steiner trees packing problem where multiple "interacting" trees have to be sought within a given graph. Depending on the interaction among trees we distinguish the vertex-disjoint Steiner trees problem, where trees cannot share nodes, from the edge-disjoint Steiner trees problem, where edges cannot be shared by trees but nodes can be members of multiple trees. Several practical problems of huge interest in network design can be mapped into these two variants, for instance, the physical design of Very Large Scale Integration (VLSI) chips. The formalism described here relies on two components edge-variables that allows us to formulate a massage-passing algorithm for the V-DStP and two algorithms for the E-DStP differing in the scaling of the computational time with respect to some relevant parameters. We will show that one of the two formalisms used for the edge-disjoint variant allow us to map the max-sum update equations into a weighted maximum matching problem over proper bipartite graphs. We developed a heuristic procedure based on the max-sum equations that shows excellent performance in synthetic networks (in particular outperforming standard multi-step greedy procedures by large margins) and on large benchmark instances of VLSI for which the optimal solution is known, on which the algorithm found the optimum in two cases and the gap to optimality was never larger than 4 %

An efficient solver for multi-objective onshore wind farm siting and network integration

Existing planning approaches for onshore wind farm siting and network integration often do not meet minimum cost solutions or social and environmental considerations. In this paper, we develop an approach for the multi-objective optimization of turbine locations and their network connection using a Quota Steiner tree problem. Applying a novel transformation on a known directed cut formulation, reduction techniques, and heuristics, we design an exact solver that makes large problem instances solvable and outperforms generic MIP solvers. Although our case studies in selected regions of Germany show large trade-offs between the objective criteria of cost and landscape impact, small burdens on one criterion can significantly improve the other criteria. In addition, we demonstrate that contrary to many approaches for exclusive turbine siting, network integration must be simultaneously optimized in order to avoid excessive costs or landscape impacts in the course of a wind farm project. Our novel problem formulation and the developed solver can assist planners in decision making and help optimize wind farms in large regions in the future

Mathematical Programming Algorithms for Spatial Cloaking

We consider a combinatorial optimization problem for spatial information cloaking. The problem requires computing one or several disjoint arborescences on a graph from a predetermined root or subset of candidate roots, so that the number of vertices in the arborescences is minimized but a given threshold on the overall weight associated with the vertices in each arborescence is reached. For a single arborescence case, we solve the problem to optimality by designing a branch-and-cut exact algorithm. Then we adapt this algorithm for the purpose of pricing out columns in an exact branch-and-price algorithm for the multiarborescence version. We also propose a branch-and-price-based heuristic algorithm, where branching and pricing, respectively, act as diversification and intensification mechanisms. The heuristic consistently finds optimal or near optimal solutions within a computing time, which can be three to four orders of magnitude smaller than that required for exact optimization. From an application point of view, our computational results are useful to calibrate the values of relevant parameters, determining the obfuscation level that is achieved

Causal Network Models of SARS-CoV-2 Expression and Aging to Identify Candidates for Drug Repurposing

Given the severity of the SARS-CoV-2 pandemic, a major challenge is to rapidly repurpose existing approved drugs for clinical interventions. While a number of data-driven and experimental approaches have been suggested in the context of drug repurposing, a platform that systematically integrates available transcriptomic, proteomic and structural data is missing. More importantly, given that SARS-CoV-2 pathogenicity is highly age-dependent, it is critical to integrate aging signatures into drug discovery platforms. We here take advantage of large-scale transcriptional drug screens combined with RNA-seq data of the lung epithelium with SARS-CoV-2 infection as well as the aging lung. To identify robust druggable protein targets, we propose a principled causal framework that makes use of multiple data modalities. Our analysis highlights the importance of serine/threonine and tyrosine kinases as potential targets that intersect the SARS-CoV-2 and aging pathways. By integrating transcriptomic, proteomic and structural data that is available for many diseases, our drug discovery platform is broadly applicable. Rigorous in vitro experiments as well as clinical trials are needed to validate the identified candidate drugs

Swimming Upstream: Identifying Proteomic Signals that Drive Transcriptional Changes using the Interactome and Multiple “-Omics” Datasets

available in PMC 2013 December 23Signaling and transcription are tightly integrated processes that underlie many cellular responses to the environment. A network of signaling events, often mediated by post-translational modification on proteins, can lead to long-term changes in cellular behavior by altering the activity of specific transcriptional regulators and consequently the expression level of their downstream targets. As many high-throughput, “-omics” methods are now available that can simultaneously measure changes in hundreds of proteins and thousands of transcripts, it should be possible to systematically reconstruct cellular responses to perturbations in order to discover previously unrecognized signaling pathways. This chapter describes a computational method for discovering such pathways that aims to compensate for the varying levels of noise present in these diverse data sources. Based on the concept of constraint optimization on networks, the method seeks to achieve two conflicting aims: (1) to link together many of the signaling proteins and differentially expressed transcripts identified in the experiments “constraints” using previously reported protein–protein and protein–DNA interactions, while (2) keeping the resulting network small and ensuring it is composed of the highest confidence interactions “optimization”. A further distinctive feature of this approach is the use of transcriptional data as evidence of upstream signaling events that drive changes in gene expression, rather than as proxies for downstream changes in the levels of the encoded proteins. We recently demonstrated that by applying this method to phosphoproteomic and transcriptional data from the pheromone response in yeast, we were able to recover functionally coherent pathways and to reveal many components of the cellular response that are not readily apparent in the original data. Here, we provide a more detailed description of the method, explore the robustness of the solution to the noise level of input data and discuss the effect of parameter values.National Cancer Institute (U.S.) ((NCI) Grant U54-CA112967)Natural Sciences and Engineering Research Council of Canada (Postgraduate scholarship)Massachusetts Institute of Technology (Eugene Bell Career Development Chair)National Cancer Institute (U.S.) (NCI integrative cancer biology program graduate fellowship

Statistical mechanics approaches to optimization and inference

Nowadays, typical methodologies employed in statistical physics are successfully applied to a huge set of problems arising from different research fields. In this thesis I will propose several statistical mechanics based models able to deal with two types of problems: optimization and inference problems. The intrinsic difficulty that characterizes both problems is that, due to the hard combinatorial nature of optimization and inference, finding exact solutions would require hard and impractical computations. In fact, the time needed to perform these calculations, in almost all cases, scales exponentially with respect to relevant parameters of the system and thus cannot be accomplished in practice. As combinatorial optimization addresses the problem of finding a fair configuration of variables able to minimize/maximize an objective function, inference seeks a posteriori the most fair assignment of a set of variables given a partial knowledge of the system. These two problems can be re-phrased in a statistical mechanics framework where elementary components of a physical system interact according to the constraints of the original problem. The information at our disposal can be encoded in the Boltzmann distribution of the new variables which, if properly investigated, can provide the solutions to the original problems. As a consequence, the methodologies originally adopted in statistical mechanics to study and, eventually, approximate the Boltzmann distribution can be fruitfully applied for solving inference and optimization problems. The structure of the thesis follows the path covered during the three years of my Ph.D. At first, I will propose a set of combinatorial optimization problems on graphs, the Prize collecting and the Packing of Steiner trees problems. The tools used to face these hard problems rely on the zero-temperature implementation of the Belief Propagation algorithm, called Max Sum algorithm. The second set of problems proposed in this thesis falls under the name of linear estimation problems. One of them, the compressed sensing problem, will guide us in the modelling of these problems within a Bayesian framework along with the introduction of a powerful algorithm known as Expectation Propagation or Expectation Consistent in statistical physics. I will propose a similar approach to other challenging problems: the inference of metabolic fluxes, the inverse problem of the electro-encephalography and the reconstruction of tomographic images