SUMMARY: We present NetworkCommons, a platform for integrating prior knowledge, omics data, and network inference methods, facilitating their usage and evaluation. NetworkCommons aims to be an infrastructure for the network biology community that supports the development of better methods and benchmarks, by enhancing interoperability and integration. AVAILABILITY AND IMPLEMENTATION: NetworkCommons is implemented in Python and offers programmatic access to multiple omics datasets, network inference methods, and benchmarking setups. It is a free software, available at https://github.com/saezlab/networkcommons, and deposited in Zenodo at https://doi.org/10.5281/zenodo.14719118.

Metabolic profiling (metabolomics) aims at measuring small molecules (metabolites) in complex samples like blood or urine for human health studies. While biomarker-based assessment often relies on a single molecule, metabolic profiling combines several metabolites to create a more complex and more specific fingerprint of the disease. However, in contrast to genomics, there is no unique metabolomics setup able to measure the entire metabolome. This challenge leads to tedious and resource consuming preliminary studies to be able to design the right metabolomics experiment. In that context, computer assisted metabolic profiling can be of strong added value to design metabolomics studies more quickly and efficiently. We propose a constraint-based modelling approach which predicts in silico profiles of metabolites that are more likely to be differentially abundant under a given metabolic perturbation (e.g. due to a genetic disease), using flux simulation. In genome-scale metabolic networks, the fluxes of exchange reactions, also known as the flow of metabolites through their external transport reactions, can be simulated and compared between control and disease conditions in order to calculate changes in metabolite import and export. These import/export flux differences would be expected to induce changes in circulating biofluid levels of those metabolites, which can then be interpreted as potential biomarkers or metabolites of interest. In this study, we present SAMBA (SAMpling Biomarker Analysis), an approach which simulates fluxes in exchange reactions following a metabolic perturbation using random sampling, compares the simulated flux distributions between the baseline and modulated conditions, and ranks predicted differentially exchanged metabolites as potential biomarkers for the perturbation. We show that there is a good fit between simulated metabolic exchange profiles and experimental differential metabolites detected in plasma, such as patient data from the disease database OMIM, and metabolic trait-SNP associations found in mGWAS studies. These biomarker recommendations can provide insight into the underlying mechanism or metabolic pathway perturbation lying behind observed metabolite differential abundances, and suggest new metabolites as potential avenues for further experimental analyses.

The correct identification of metabolic activity in tissues or cells under different conditions can be extremely elusive due to mechanisms such as post-transcriptional modification of enzymes or different rates in protein degradation, making difficult to perform predictions on the basis of gene expression alone. Context-specific metabolic network reconstruction can overcome some of these limitations by leveraging the integration of multi-omics data into genome-scale metabolic networks (GSMN). Using the experimental information, context-specific models are reconstructed by extracting from the generic GSMN the sub-network most consistent with the data, subject to biochemical constraints. One advantage is that these context-specific models have more predictive power since they are tailored to the specific tissue, cell or condition, containing only the reactions predicted to be active in such context. However, an important limitation is that there are usually many different sub-networks that optimally fit the experimental data. This set of optimal networks represent alternative explanations of the possible metabolic state. Ignoring the set of possible solutions reduces the ability to obtain relevant information about the metabolism and may bias the interpretation of the true metabolic states. In this work we formalize the problem of enumerating optimal metabolic networks and we introduce DEXOM, an unified approach for diversity-based enumeration of context-specific metabolic networks. We developed different strategies for this purpose and we performed an exhaustive analysis using simulated and real data. In order to analyze the extent to which these results are biologically meaningful, we used the alternative solutions obtained with the different methods to measure: 1) the improvement of in silico predictions of essential genes in Saccharomyces cerevisiae using ensembles of metabolic network; and 2) the detection of alternative enriched pathways in different human cancer cell lines. We also provide DEXOM as an open-source library compatible with COBRA Toolbox 3.0, available at https://github.com/MetExplore/dexom.

Over-representation analysis (ORA) is one of the commonest pathway analysis approaches used for the functional interpretation of metabolomics datasets. Despite the widespread use of ORA in metabolomics, the community lacks guidelines detailing its best-practice use. Many factors have a pronounced impact on the results, but to date their effects have received little systematic attention. Using five publicly available datasets, we demonstrated that changes in parameters such as the background set, differential metabolite selection methods, and pathway database used can result in profoundly different ORA results. The use of a non-assay-specific background set, for example, resulted in large numbers of false-positive pathways. Pathway database choice, evaluated using three of the most popular metabolic pathway databases (KEGG, Reactome, and BioCyc), led to vastly different results in both the number and function of significantly enriched pathways. Factors that are specific to metabolomics data, such as the reliability of compound identification and the chemical bias of different analytical platforms also impacted ORA results. Simulated metabolite misidentification rates as low as 4% resulted in both gain of false-positive pathways and loss of truly significant pathways across all datasets. Our results have several practical implications for ORA users, as well as those using alternative pathway analysis methods. We offer a set of recommendations for the use of ORA in metabolomics, alongside a set of minimal reporting guidelines, as a first step towards the standardisation of pathway analysis in metabolomics.

The reduction of energy consumption in buildings is one of the goals to improve energy efficiency. One way to achieve energy savings in buildings is to develop intelligent control heating strategies that are able to reduce the power consumption by predicting the behavior of the thermal dynamics under different control schemes. One way to accomplish this is by means of learning fuzzy rules using the data collected from different sensors installed in buildings to generate regression models that are accurate and interpretable, so the generated models can be understood by the experts who approve the energy-saving schemes. However, one important issue is the generation of accurate knowledge bases of fuzzy rules for regression that can scale with the large amount of information generated by the many sensors installed in buildings, which will continue to grow in the coming years. For this purpose, in this paper we evaluate the scalability of two genetic fuzzy systems, FRULER and S-FRULER in the domain of thermal dynamics in buildings, using real data from a residential college at the USC.

In this paper we present a hybrid approach for automatic composition of Web services that generates semantic input-output based compositions with optimal end-to-end QoS, minimizing the number of services of the resulting composition. The proposed approach has four main steps: (1) generation of the composition graph for a request; (2) computation of the optimal composition that minimizes a single objective QoS function; (3) multi-step optimizations to reduce the search space by identifying equivalent and dominated services; and (4) hybrid local-global search to extract the optimal QoS with the minimum number of services. An extensive validation with the datasets of the Web Service Challenge 2009-2010 and randomly generated datasets shows that: (1) the combination of local and global optimization is a general and powerful technique to extract optimal compositions in diverse scenarios; and (2) the hybrid strategy performs better than the state-of-the-art, obtaining solutions with less services and optimal QoS.

In this paper we present a theoretical analysis of graph-based service composition in terms of its dependency with service discovery. Driven by this analysis we define a composition framework by means of integration with fine-grained I/O service discovery that enables the generation of a graph-based composition which contains the set of services that are semantically relevant for an input-output request. The proposed framework also includes an optimal composition search algorithm to extract the best composition from the graph minimising the length and the number of services, and different graph optimisations to improve the scalability of the system. A practical implementation used for the empirical analysis is also provided. This analysis proves the scalability and flexibility of our proposal and provides insights on how integrated composition systems can be designed in order to achieve good performance in real scenarios for the web.

This paper presents a hybrid approach for automatic composition of Web services that generates semantic input-output matching compositions minimizing the number of services and optimizing the global QoS. The proposed approach has four main steps: 1) generation of the composition graph for a request, 2) computation of the optimal QoS of the composition graph, 3) multi-step optimizations of the graph to identify equivalent and dominated services, and 4) hybrid local-global search to extract the optimal QoS with the minimum number of services. A validation with the datasets of the Web Service Challenge 2009-2010 is also provided.

Service Oriented Architectures and web service technology are becoming popular in recent years. As more web services can be used over the Internet, the need to find efficient algorithms for web services composition that can deal with large amounts of services becomes important. These algorithms must deal with different issues like performance, semantics or user restrictions. In this paper we present an A* algorithm which solves the problem of semantic input-output message structure matching for web service composition. Given are quest, a service dependency graph with a subset of the original services from an external repository is dynamically generated. Then, the A* search algorithm is used to find a minimal composition that satisfies the user request. Moreover, in order to improve the performance, a set of dynamic optimization techniques has been implemented over the search process. A full experimental validation with eight different public repositories has been done showing a good performance as in all tests as the algorithm finds a valid solution with minimal number of services and execution path.