Tutorial

The EVEX website provides summarized information on various bio-molecular events, accounting for lexical variation of gene/protein symbols and dealing with synonymy and abbreviations. Both direct and indirect associations can be retrieved, and homology-based generalizations provide the opportunity to retrieve information on entire gene families.

• Finding direct and indirect associations
• Retrieving sentences by event type
• Homology-based inference

Finding direct and indirect associations

Simply type a gene or protein symbol to retrieve relevant information from the literature on the 'symbol search' tab. If you want the result set to be filtered for a specific gene or protein from a given organism, use the 'ID search' tab. Here, you may also enter external identifiers such as an Entrez Gene ID or a UniProt ID.

Suppose we are interested in the budding yeast gene Mec1, we can issue a search to retrieve all relevant information on this gene:
http://evexdb.org/search/canonical/?search=Mec1
The site shows all text mining evidence for regulation targets (e.g. RAD9), regulators (e.g. Pch2) and binding partners (e.g. Ddc2) of Mec1, displaying also whether the confidence of the extracted information is very high, high, average, low or very low.

Selecting the target RAD9, the website visualises all event structures expressing regulation of RAD9 by Mec1:
http://evexdb.org/ggps/canonical/regulates/?keyword1=3993&keyword2=12515
This enables a quick overview of the mechanisms through which the regulation is established, which can have a certain polarity (positive/negative) and may involve physical events such as phosphorylation or DNA binding.

Exploring the relationship between RAD9 and Mec1 further, EVEX enables a search of all events linking these two genes through any direct or indirect association:
http://evexdb.org/search/canonical/?search=RAD9,mec1
This search can easily be selected using the 'Related searches' box on the right. The resulting page not only displays the regulation mechanisms, but also provides evidence for a binding event between RAD9 and Mec1. Further, potential co-regulations are listed, enumerating targets that are regulated by both genes, such as Rad53. Other indirect associations, such as common regulators and binding partners, can be retrieved equally fast.

Finally, the website provides additional features to fetch indirectly associated information relevant to a specific event, by allowing the retrieval of nested and parent interactions. For example, we can access the details for Mec1's positive regulation of the RAD9 phosphorylation. This page lists the phosphorylation of RAD9 as a nested interaction, which has its own unique ID and evidence page:
http://evexdb.org/canonical/events/516624/
From this page, we learn that this specific phosphorylation event has many different potential regulators.

Retrieving sentences by event type

When querying EVEX for a particular gene or protein, the resulting overview page additionally contains links to relevant sentences describing specific event types such as localization, gene expression, phosphorylation, methylation and protein catabolism, as well as binding and regulation events without a second argument. While these events incorporate only a single gene/protein and may not be very informative by themselves, they are highly relevant for information retrieval purposes, finding interesting sentences and articles describing specific processes where the gene/protein of interest is involved in.

At the bottom of the overview page, a similar and even more general set of sentences can be found, providing pointers to relevant literature while still requiring manual analysis to determine the exact type of information. Such sentences may include information on relevant experimental studies, related diseases or general functions and pathways:
http://evexdb.org/search/canonical/general/?search=3993

Homology-based inference

Instead of only looking at the information for one particular gene/protein symbol as described previously, we can extend the search through known gene families, such as those from Ensembl Genomes, and retrieve information on homologous genes and their synonyms. The generated listings of regulators and binding partners are structured in exactly the same way as before, but this time each symbol refers to a whole gene family rather than just one gene name:
http://evexdb.org/search/egenomes/?search=Mec1

The family profile lists the genes in the families and their organisms, linking to the authoritive resources such as Entrez Gene, Ensembl and the Taxonomy database at NCBI:
http://evexdb.org/gene-family/egenomes/127742/

The EVEX website contains several distinct methods of defining gene families, including HomoloGene (eukaryots), Ensembl (vertebrates) and Ensembl Genomes (metazoa, plants, protists, fungi, bacteria). Each generalization caters for specific use-cases. For example, Ensembl Genomes uses rather coarse grained families resulting in a family of 21 evolutionarily conserved genes for the budding yeast gene Mec1, its mammalian ATR orthologs and genes from green algea and Arabidopsis. In contrast, the corresponding family defined by HomoloGene only includes the 6 conserved Mec1 genes in the Ascomycota.