In the Spotlight
WikiPathways: One of the Database Resources on AltTox
Around 10,000 different proteins have been identified in each of eleven examined human cell lines (Beck et al., 2011; Geiger et al., 2012). These cellular proteins are not sloshing around in a chaotic fashion, but are highly organized into sub-cellular domains or compartments, and their activities are part of one or more cellular networks or pathways [for recent reviews see Byron & Frame, 2016 and Villaseñor et al., 2016]. Cellular pathways are the interconnected, complex, and sometimes redundant representations of the transformations and interactions of a particular group of molecules that can take place inside a cell. “The networks of proteins, and their interactions, are dynamic, mechanosensitive, and extremely complex” (Byron & Frame, 2016).
Many cellular pathways have been “mapped,” while others are in various stages of discovery, or awaiting discovery. For example, a number of signal transduction pathways, which illustrate the networks of molecular interactions involved in regulating various cellular functions, have been elucidated [for recent reviews see Dohlman, 2016 and Vlasova & Bohjanen, 2016]. The importance of identifying the cellular pathways related to toxicity or adverse cellular events has also been recognized; these are called toxicity pathways. “In this context, a toxicity pathway is a normal biological pathway that becomes perturbed beyond the point of homeostatic correction leading to toxicity” (Willett, 2014).
Cell-based research studies are often designed to elucidate the function of one protein or part of a pathway, while understanding how that “part” fits into the bigger picture may be essential to understanding the relevance of a particular protein to the overall function of the cell. Thus, pathway mapping and pathway databases provide researchers with the tools needed to organize and understand the role(s) of individual proteins, and their genes, in the milieu found inside a cell.
The WikiPathways Database
WikiPathways is an interesting example of a pathways database. Kutmon, et al. (2016) reported substantial growth in the content and features of this database since its launch in 2008 “as an experiment to see if crowdsourcing could work for a pathway archive.”
They describe WikiPathways as starting out with 500 pathways across six species, and now containing over 2300 pathways across over 25 species. “The human pathway collection is the largest and most active collection by species, having increased 6-fold to include 640 pathways…. Our advantage going forward lies in our scalable, community-based curation and unrestricted pathway model, accepting any pathway that researchers find useful in their work.”
Each pathway at WikiPathways has a dedicated wiki page, displaying the current diagram, description, references, download options, version history, and component gene and protein lists. Any pathway can be edited from within its wiki page by activating an embedded pathway editor. After editing, an updated pathway image is displayed on the wiki page along with the version history and list of component genes and proteins. Users can easily monitor and undo changes, compare differences and search for overlapping pathways. Using the search feature, one can locate particular pathways by name, by the genes and proteins they contain, or by the text displayed in their descriptions and comments. One can also browse the collection of pathways with combinations of species names and ontology-based categories. The pathway content at WikiPathways is freely available for download in a variety of data and image formats….
Today’s featured pathway” on a recent visit to WikiPathways was the ATM Signaling Pathway shown here.
Tools and applications
An interesting and recent addition to WikiPathways is TissueAnalyzer, which “combine[s] the pathway knowledge from WikiPathways with baseline expression data for 27 different tissues from Expression Atlas to study the activity of biological pathways in a specific tissue. TissueAnalyzer provides a ranked table of pathways per tissue based on their median expression and the active genes in each pathway.”
An application, created in WikiPathways by Jennen, et al. (2010) with potential utility in toxicology, is the integrated biotransformation pathway maps for the visualization of drug metabolism related changes in protein expression.
Software was needed to transform pathway maps for visualization as networks. A WikiPathways app for Cytoscape was developed as a tool for the visualization of biological pathways as networks and for network analysis. Kutmon, et al. (2014) uses the cardiac hypertrophic response pathway from WikiPathways to demonstrate a pathway loaded as a network and illustrates several types of network analysis.
Future of WikiPathways
Only several of the many tools and feature of WikiPathways are highlighted here. For more WikiPathways features and how to get involved, see WikiPathways, Kutmon, et al. (2016), and Kelder, et al., (2012).
Scientists at the Gladstone Institutes, where WikiPathways was conceived and launched, say they will “continue to build tools and resources to support WikiPathways.”
The Databases Section of AltTox
The publication of the 2016 Database issue of Nucleic Acids Research (NAS) inspired us to update the Databases section of AltTox, which now contains more than 20 new entries from various sources. Database listings on AltTox are grouped according to the following categories:
- Alternatives Databases
- Scientific/Technical Literature Databases
- Database Journals
- Chemical Toxicity Databases
- Grants/Awards Databases
- Genome and Other Biomedical Databases
- Bioinformatics Databases
- Cell Line Databases
- Genomics Databases
- Drug Discovery Databases
- Single Nucleotide Polymorphisms (SNPs)
- RNA and RNAi
- Proteins and Proteomics
- Pathway Databases
- Database Lists
- Pharmacokinetics and Pharmacogenomics Databases
- Biomedical Simulation Projects/Software
- Policy Databases
The AltTox Databases page is provided as a resource for our online community. Your suggestions for new listings, corrections, and organizational recommendations are welcome; these can be sent to firstname.lastname@example.org.