MOTIVATION: Binary (or Boolean) matrices provide a common effective data representation adopted in several domains of computational biology, especially for investigating cancer and other human diseases. For instance, they are used to summarize genetic aberrations-copy number alterations or mutations-observed in cancer patient cohorts, effectively highlighting combinatorial relations among them. One of these is the tendency for two or more genes not to be co-mutated in the same sample or patient, i.e. a mutual-exclusivity trend. Exploiting this principle has allowed identifying new cancer driver protein-interaction networks and has been proposed to design effective combinatorial anti-cancer therapies rationally. Several tools exist to identify and statistically assess mutual-exclusive cancer-driver genomic events. However, these tools need to be equipped with robust/efficient methods to sort rows and columns of a binary matrix to visually highlight possible mutual-exclusivity trends. RESULTS: Here, we formalize the mutual-exclusivity-sorting problem and present MutExMatSorting: an R package implementing a computationally efficient algorithm able to sort rows and columns of a binary matrix to highlight mutual-exclusivity patterns. Particularly, our algorithm minimizes the extent of collective vertical overlap between consecutive non-zero entries across rows while maximizing the number of adjacent non-zero entries in the same row. Here, we demonstrate that existing tools for mutual-exclusivity analysis are suboptimal according to these criteria and are outperformed by MutExMatSorting. AVAILABILITY AND IMPLEMENTATION: https://github.com/AleVin1995/MutExMatSorting. SUPPLEMENTARY INFORMATION: Supplementary data are available at Bioinformatics online.

Black-box topology optimization (BBTO) uses evolutionary algorithms and other soft computing techniques to generate near-optimal topologies of mechanical structures. Although evolutionary algorithms are widely used to compensate the limited applicability of conventional gradient optimization techniques, methods based on BBTO have been criticized due to numerous drawbacks. In this article, we discuss topology optimization as a black-box optimization problem. We review the main BBTO methods, discuss their challenges and present approaches to relax them. Dealing with those challenges effectively can lead to wider applicability of topology optimization, as well as the ability to tackle industrial, highly constrained, nonlinear, many-objective, and multimodal problems. Consequently, future research in this area may open the door for innovating new applications in science and engineering that may go beyond solving classical optimization problems of mechanical structures. Furthermore, algorithms designed for BBTO can be added to existing software toolboxes and packages of topology optimization.

A configuration design problem in mechanical engineering involves finding an optimal assembly of components and joints that realizes some desired performance criteria. Such a problem is a discrete, constrained, and black-box optimization problem. A novel method is developed to solve the problem by applying Bivariate Marginal Distribution Algorithm (BMDA) and constraint programming (CP). BMDA is a type of Estimation of Distribution Algorithm (EDA) that exploits the dependency knowledge learned between design variables without requiring too many fitness evaluations, which tend to be expensive for the current application. BMDA is extended with adaptive chi-square testing to identify dependencies and Gibbs sampling to generate new solutions. Also, repair operations based on CP are used to deal with infeasible solutions found during search. The method is applied to a vehicle suspension design problem and is found to be more effective in converging to good solutions than a genetic algorithm and other EDAs. These contributions are significant steps towards solving the difficult problem of configuration design in mechanical engineering with evolutionary computation.

Performance characteristics of a complex system in different configurations are expensive to obtain due to the cost of sampling the system performance. We introduce ModelMap, a novel transfer learning technique for the performance modeling of configurable systems. ModelMap captures many explicit and latent types of dynamic system evolution, including configuration changes, scaling and hardware upgrades, by deriving and modeling directly these kinds of incremental transformations between system and/or application instances, over time. Modeling these transformations allows us to build accurate models for new configuration instances with just a few samples, and to interpolate across legacy models to build new models with no new samples at all. We experimentally test our method on a variety of system performance modeling and optimization scenarios. Compared to using conventional direct and incremental modeling techniques, our method achieves higher accuracy by up to an order of magnitude when the sampling budget is extremely limited, in particular between 0% to 5% of an exhaustive sampling budget. We also show how our method can be used to quickly derive an accurate resource allocation split that optimizes a given overall performance goal for co-hosted applications in a virtualized environment.

Motivation: Large pharmacogenomic screenings integrate heterogeneous cancer genomic datasets as well as anti-cancer drug responses on thousand human cancer cell lines. Mining this data to identify new therapies for cancer sub-populations would benefit from common data structures, modular computational biology tools and user-friendly interfaces. Results: We have developed GDSCTools: a software aimed at the identification of clinically relevant genomic markers of drug response. The Genomics of Drug Sensitivity in Cancer (GDSC) database (www.cancerRxgene.org) integrates heterogeneous cancer genomic datasets as well as anti-cancer drug responses on a thousand cancer cell lines. Including statistical tools (analysis of variance) and predictive methods (Elastic Net), as well as common data structures, GDSCTools allows users to reproduce published results from GDSC and to implement new analytical methods. In addition, non-GDSC data resources can also be analysed since drug responses and genomic features can be encoded as CSV files. Contact: [email protected] or saezrodriguez.rwth-aachen.de or [email protected]. Supplementary information: Supplementary data are available at Bioinformatics online.

In aerodynamics related design, analysis and optimization problems, flow fields are simulated using computational fluid dynamics (CFD) solvers. However, CFD simulation is usually a computationally expensive, memory demanding and time consuming iterative process. These drawbacks of CFD limit opportunities for design space exploration and forbid interactive design. We propose a general and flexible approximation model for real-time prediction of non-uniform steady laminar flow in a 2D or 3D domain based on convolutional neural networks (CNNs). We explored alternatives for the geometry representation and the network architecture of CNNs. We show that convolutional neural networks can estimate the velocity field two orders of magnitude faster than a GPU-accelerated CFD solver and four orders of magnitude faster than a CPU-based CFD solver at a cost of a low error rate. This approach can provide immediate feedback for real-time design iterations at the early stage of design. Compared with existing approximation models in the aerodynamics domain, CNNs enable an efficient estimation for the entire velocity field. Furthermore, designers and engineers can directly apply the CNN approximation model in their design space exploration algorithms without training extra lower-dimensional surrogate models.

BACKGROUND: Networks are popular and powerful tools to describe and model biological processes. Many computational methods have been developed to infer biological networks from literature, high-throughput experiments, and combinations of both. Additionally, a wide range of tools has been developed to map experimental data onto reference biological networks, in order to extract meaningful modules. Many of these methods assess results' significance against null distributions of randomized networks. However, these standard unconstrained randomizations do not preserve the functional characterization of the nodes in the reference networks (i.e. their degrees and connection signs), hence including potential biases in the assessment. RESULTS: Building on our previous work about rewiring bipartite networks, we propose a method for rewiring any type of unweighted networks. In particular we formally demonstrate that the problem of rewiring a signed and directed network preserving its functional connectivity (F-rewiring) reduces to the problem of rewiring two induced bipartite networks. Additionally, we reformulate the lower bound to the iterations' number of the switching-algorithm to make it suitable for the F-rewiring of networks of any size. Finally, we present BiRewire3, an open-source Bioconductor package enabling the F-rewiring of any type of unweighted network. We illustrate its application to a case study about the identification of modules from gene expression data mapped on protein interaction networks, and a second one focused on building logic models from more complex signed-directed reference signaling networks and phosphoproteomic data. CONCLUSIONS: BiRewire3 it is freely available at https://www.bioconductor.org/packages/BiRewire/ , and it should have a broad application as it allows an efficient and analytically derived statistical assessment of results from any network biology tool.

We introduce Ensemble, a runtime framework and associated tools for building application performance models on-the-fly. These dynamic performance models can be used to support complex, highly dimensional resource allocation, and/or what-if performance inquiry in modern heterogeneous environments, such as data centers and Clouds. Ensemble combines simple, partially specified, and lower-dimensionality models to provide good initial approximations for higher dimensionality application performance models. We evaluated Ensemble on industry-standard and scientific applications. The results show that Ensemble provides accurate, fast, and flexible performance models even in the presence of significant environment variability.

MOTIVATION: Studying combinatorial patterns in cancer genomic datasets has recently emerged as a tool for identifying novel cancer driver networks. Approaches have been devised to quantify, for example, the tendency of a set of genes to be mutated in a 'mutually exclusive' manner. The significance of the proposed metrics is usually evaluated by computing P-values under appropriate null models. To this end, a Monte Carlo method (the switching-algorithm) is used to sample simulated datasets under a null model that preserves patient- and gene-wise mutation rates. In this method, a genomic dataset is represented as a bipartite network, to which Markov chain updates (switching-steps) are applied. These steps modify the network topology, and a minimal number of them must be executed to draw simulated datasets independently under the null model. This number has previously been deducted empirically to be a linear function of the total number of variants, making this process computationally expensive. RESULTS: We present a novel approximate lower bound for the number of switching-steps, derived analytically. Additionally, we have developed the R package BiRewire, including new efficient implementations of the switching-algorithm. We illustrate the performances of BiRewire by applying it to large real cancer genomics datasets. We report vast reductions in time requirement, with respect to existing implementations/bounds and equivalent P-value computations. Thus, we propose BiRewire to study statistical properties in genomic datasets, and other data that can be modeled as bipartite networks. AVAILABILITY AND IMPLEMENTATION: BiRewire is available on BioConductor at http://www.bioconductor.org/packages/2.13/bioc/html/BiRewire.html. SUPPLEMENTARY INFORMATION: Supplementary data are available at Bioinformatics online.

SUMMARY: Drug versus Disease (DvD) provides a pipeline, available through R or Cytoscape, for the comparison of drug and disease gene expression profiles from public microarray repositories. Negatively correlated profiles can be used to generate hypotheses of drug-repurposing, whereas positively correlated profiles may be used to infer side effects of drugs. DvD allows users to compare drug and disease signatures with dynamic access to databases Array Express, Gene Expression Omnibus and data from the Connectivity Map. AVAILABILITY AND IMPLEMENTATION: R package (submitted to Bioconductor) under GPL 3 and Cytoscape plug-in freely available for download at www.ebi.ac.uk/saezrodriguez/DVD/.

We investigated the possibility of gaining information on the mode of action of a set of compounds by means of Gene Ontology (GO) enrichment analysis. To this aim, we developed a new method, based on fuzzy-sets, which is able to compute sets of genes that are consistently differentially expressed when treating cells with the analyzed compounds. Then a Gene Ontology enrichment analysis is performed on these sets. The method has been tested on several different groups of drugs, whose similarity in mode of action has been predicted by a gene-expression based, unsupervised, approach and verified by searching literature. The obtained results show that GO terms that are overrepresented in these fuzzy sets provide a quick and "easy-tointerpret" view of the mode of action of the analyzed drugs.

We present the results of the enumeration of Costas arrays of order 28: all arrays found are accounted for by the Golomb and Welch construction methods, making 28 the first order (larger than 5) for which no sporadic Costas arrays exist. The enumeration was performed on several computer clusters and required the equivalent of 70 years of single CPU time.

This correspondence presents the results of the enumeration of Costas arrays of order$27$: all arrays found, except for one, are accounted for by the Golomb and Welch construction methods.

In this work a multi-step approach for clustering assessment, visualization and data validation is introduced. Three main approaches for data clustering are used and compared: K-means, self organizing maps and probabilistic principal surfaces. A model explorer approach with different similarity measures is used to obtain the best parameters of the methods. The approach is used to identify genes periodically expressed in tumors related to the human cell cycle. Finally, clusters are validated by using GO term information.

In this paper a Toolbox to generate and to analyze linear, non-linear, delayed and convolved mixtures of real source signals is presented. From one hand, in fact, a simple interface based on a physical model has been implemented and stereo, dolby, delayed, and convolved mixtures can be generated. On the other hand a blind source separation analysis can be accomplished. In fact, a novel separation algorithm (i.e. APDP) is included in the Toolbox. Several experiments to separate delayed mixtures of real instruments are made. Three musical recordings of different instrumental scores are mixed and analyzed by using the Toolbox. Several comparisons with known methods are made.