Pathway databases and tools for their exploitation: benefits, current limitations and challenges

Abstract

In past years, comprehensive representations of cell signalling pathways have been developed by manual curation from literature, which requires huge effort and would benefit from information stored in databases and from automatic retrieval and integration methods. Once a reconstruction of the network of interactions is achieved, analysis of its structural features and its dynamic behaviour can take place. Mathematical modelling techniques are used to simulate the complex behaviour of cell signalling networks, which ultimately sheds light on the mechanisms leading to complex diseases or helps in the identification of drug targets. A variety of databases containing information on cell signalling pathways have been developed in conjunction with methodologies to access and analyse the data. In principle, the scenario is prepared to make the most of this information for the analysis of the dynamics of signalling pathways. However, are the knowledge repositories of signalling pathways ready to realize the systems biology promise? In this article we aim to initiate this discussion and to provide some insights on this issue.

Enter the matrix: factorization uncovers knowledge from omics Names/Affiliations

“…The computational differences between these algorithms have been described in numerous reviews (Berry et al, 2007;Devarajan, 2008;Ochs and Fertig, 2012;Wang and Zhang, 2013) . Perhaps the most prominent of methods is principal component analysis (PCA).…”

“…This often results in a two-step process where differential expression analysis is used to identify genes, and then interpretation occurs in the context of pathways gleaned from the literature by human curation (Bauer-Mehren et al, 2009;Tsui et al, 2007) . A challenge with such pathway-level interpretations is that they often lack important contextual information (Khatri et al, 2012) : a gene may be part of a pathway but it may not be expressed in certain cellular contexts.…”

“…In vitro or in vivo experimentation was once the only way to uncover new biological knowledge. High-throughput technologies have ushered in a data deluge era in biology (Bell et al, 2009;Sagoff, 2012) and empowered in silico experimentation. Specifically, new insights are often revealed through computation analysis of this data prior to experimental validation.…”

A Cross-Format Framework for Consistent Information Integration among Molecular Pathways and Ontologies

“…Biomedical ontologies are being created to provide a semantic context for the molecular species that they contain. The current advances in both topics suggest an information integration cycle based on shared knowledge-bases [1]. One can envision ontology resources, such as ChEBI [2] and BioPortal [3], defining the biological context of the pathways in a machine-readable format.…”

Uniform Curation Protocol of Metazoan Signaling Pathways to Predict Novel Signaling Components

“…Accordingly, several signaling pathway databases have been generated manually by collecting relevant data from the literature [11]. However, so far most of them lack those key features (e.g., uniform pathway curation across more than one species) that would be necessary for transferring signaling pathway membership information between species [10].…”