Reactive Metabolite Target Protein Database - FAQs 1. What information is in the database? Currently the database contains information based on: 40 small molecule chemical agents (pro-toxins) representing a range of chemically-reactive electrophilic metabolites (epoxides, quinones, Michael acceptors, acylating agents); 3 animal species; 8 target tissues; 313 different (non-redundant) target proteins; 82 literature references. 2. What general searches are available? A. "View all the small molecules in the database." Clicking on this link will generate a report containing the names and structures of all chemical agents included in the database. B. "List of all protein names/synonyms in the database." Clicking on this link will generate a list of all the proteins included in the database. Many proteins have multiple names; these are treated as equivalent (redundant) and are grouped together under a single Protein ID number for that protein. (The Protein ID number is an arbitrary but unique code number that is used internally in this database). Proteins having the same name but coming from different species are given different Protein ID numbers. C. "If protein name contains...." If you are not certain of the full correct name of a protein, you can enter part of the name after the phrase "If protein name contains" and click on "Find all entries." For example, enter tran or dehyd to see what search results are returned. D. "If author name contains...." You can also find articles by a given author by typing all or part of an author's surname after the phrase "If author name contains" and clicking on "Find all entries." 3. How do I construct a custom search? The search page contains four pull-down menus. The first one lists all the chemicals in the database and allows you to select any one of them to be used as a criterion of a search. If you don't select a single chemical, the default option is to select "any(all)" of them. Custom searches can be organized by chemical agent, animal species, target tissue, or by specific proteins. For example: A. Which proteins are targeted by metabolites of acetaminophen? Search = < acetaminophen, any, any, any > B. Which proteins in the mouse have been identified as reactive metabolite targets? Search = < any, mouse, any, any > C. Which chemicals are known to modify kidney proteins? Search = < any, any, kidney, any > D. Which chemicals covalently modify glutamate dehydrogenase? Search = < any, any, any, glutamate dehydrogenase > Selecting a protein name but leaving the chemical, species and tissue selections set to their default values will produce a report listing all chemicals that modify that particular protein in any tissue of any species in the database. Using the default value of "any(all)" in each of the four pull-down categories is the equivalent of saying "search this database to find all known target proteins for any chemical in any tissue in any species covered in the database." The product of this search will be a list of every protein in the database. This same search can also be done using the general search function "List of all protein names/synonyms in the database." (see 1.B. above). 4. Are Boolean searches possible? Yes, "and" searches are possible. For example: A. Which proteins are targeted by metabolites of acetaminophen in the rat? Search = < acetaminophen, rat, any, any > B. Which chemicals are known to modify proteins in mouse lung? Search = < any, mouse, lung, any > 5. What is the Commonality Matrix? (under development). This function provides an N x N matrix, where N is the number of chemicals having entries in the database. Each diagonal element in the matrix gives the total number of non-redundant proteins that have been identified to be targeted by the chemical corresponding to that row and that column of the matrix; clicking this number will produce a report listing all those proteins. Each off-diagonal element gives the number of proteins that are targeted by the two chemicals corresponding the row and column of the matrix, and this number is again a hyperlink that will generate a list of those proteins. A word of caution. At this time the commonality matrix contains many zeros in the off-diagonal positions. This is simply an indication of the current status of the field and its literature. While there have been many studies reporting the identities of reactive metabolilte target proteins, the small number of proteins identified for most individual agents makes it difficult to discern whether there is a subset of proteins that are commonly targeted by numerous reactive metabolites. The reactive metabolite target protein database (TPDB) - a web-accessible resource. Robert P Hanzlik, Yakov M Koen, Bhargav Theertham, Yinghua Dong and Jianwen Fang. BMC Bioinformatics 2007, 8:95 doi:10.1186/1471-2105-8-95 http://www.biomedcentral.com/1471-2105/8/95