Pathway-centric approaches are widely used to interpret and contextualize -omics data. However, databases contain different representations of the same biological pathway, which may lead to different results of statistical enrichment analysis and predictive models in the context of precision medicine. We have performed an in-depth benchmarking of the impact of pathway database choice on statistical enrichment analysis and predictive modeling. We analyzed five cancer datasets using three major pathway databases and developed an approach to merge several databases into a single integrative one: MPath. Our results show that equivalent pathways from different databases yield disparate results in statistical enrichment analysis. Moreover, we observed a significant dataset-dependent impact on the performance of machine learning models on different prediction tasks. In some cases, MPath significantly improved prediction performance and also reduced the variance of prediction performances. Furthermore, MPath yielded more consistent and biologically plausible results in statistical enrichment analyses. In summary, this benchmarking study demonstrates that pathway database choice can influence the results of statistical enrichment analysis and predictive modeling. Therefore, we recommend the use of multiple pathway databases or integrative ones.

The VERCE project has pioneered an e-Infrastructure to support researchers using established simulation codes on high-performance computers in conjunction with multiple sources of observational data. This is accessed and organised via the VERCE science gateway that makes it convenient for seismologists to use these resources from any location via the Internet. Their data handling is made flexible and scalable by two Python libraries, ObsPy and dispel4py and by data services delivered by ORFEUS and EUDAT. Provenance driven tools enable rapid exploration of results and of the relationships between data, which accelerates understanding and method improvement. These powerful facilities are integrated and draw on many other e-Infrastructures. This paper presents the motivation for building such systems, it reviews how solid-Earth scientists can make significant research progress using them and explains the architecture and mechanisms that make their construction and operation achievable. We conclude with a summary of the achievements to date and identify the crucial steps needed to extend the capabilities for seismologists, for solid-Earth scientists and for similar disciplines.

The DARE platform has been designed to help research developers deliver user-facing applications and solutions over diverse underlying e-infrastructures, data and computational contexts. The platform is Cloud-ready, and relies on the exposure of API, which are suitable for raising the abstraction level and hiding complexity. It implements the cataloguing and execution of fine-grained and Python-based dispel4py workflows as services. Reflection is achieved via a logical knowledge base, comprising multiple internal catalogues, registries and semantics, while it supports persistent and pervasive data provenance. This paper presents design and implementation aspects of the DARE platform, as well as it provides directions for future development.

Background: Pathway-centric approaches are widely used to interpret and contextualize -omics data. However, databases contain different representations of the same biological pathway, which may lead to different results of statistical enrichment analysis and predictive models in the context of precision medicine. Results:We have performed an in-depth benchmarking of the impact of pathway database choice on statistical enrichment analysis and predictive modeling. We analyzed five cancer datasets using three major pathway databases and developed an approach to merge several databases into a single integrative database: MPath. Our results show that equivalent pathways from different databases yield disparate results in statistical enrichment analysis. Moreover, we observed a significant dataset-dependent impact on performance of machine learning models on different prediction tasks. Further, MPath significantly improved prediction performance and reduced the variance of prediction performances in some cases. At the same time, MPath yielded more consistent and biologically plausible results in the statistical enrichment analyses. Finally, we implemented a software package designed to make our comparative analysis with these and additional databases fully reproducible and to facilitate the update of our integrative pathway resource in the future. Conclusion:This benchmarking study demonstrates that pathway database choice can influence the results of statistical enrichment analysis and prediction modeling. Therefore, we recommend the use of multiple pathway databases or the use of integrative databases. 2/21

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