 Welcome to this tutorial about the Rear Knowledge Base, in which we will guide you through the Rear Web Interface and the Reaction Pages. Rear is an expected curated knowledge base of chemical and transport reactions of biological interest, and the standard for enzyme and transporter annotation in the Uniprot Knowledge Base. Rear describes enzyme-catalyzed reactions in a computationally tractable manner and uses the chemical dictionary KEBI for small chemical compounds to describe reaction participants. To learn more on these concepts, we recommend that you watch our previous video. We'll provide a link to that video in the info box. In this tutorial, we will learn how to discover and explore biochemical knowledge using Rear. Let's start with a cup of coffee and learn more about caffeine. This is the home page of the Rear website. We can search Rear by reaction participant name or synonym by different identifier types, such as KEBI, Rear, or enzyme classification number, or by specifying the Inche key, a computer readable representation of a reaction participant's chemical structure. Let's start by searching by name. We type caffeine. In order to retrieve reactions involving caffeine, we can just enter this word in the simple quick search interface. The simple search returns seven reactions. It means that the word caffeine has been found somewhere in the data of these seven reactions. We can now refine our search by browsing the molecules that match the query. It tells us that two molecules match our query, and as expected, we find caffeine as the first match. The second was found because one of its synonyms is 8-oxy-caffeine. Let's click on the six reactions of caffeine, and we come back to the results page, but we now only see the reactions involving caffeine with this KEBI identifier. The text search box is now filled with our new query. If we click on the advanced search, we can see that the form is already populated with our existing search term, allowing us to refine our search by adding new constraints. For instance, we can retrieve the rear reactions that have already been curated in Uniprot KEBI. To do this, we select the Uniprot KEBI topic and use a star as a wildcard for any protein. This refined search returns five reactions involving caffeine. Let's take a look at the reaction transforming CO bromine to caffeine. We can access the reaction page by clicking on the rear identifier. A reaction page is composed of five parts. Enzyme information, the 2D structure of the molecules involved in the reaction, information and reaction participants, links to other resources, and finally, the bibliographic references that have been used to curate this reaction. We will now take a closer look at some of these sections. The 2D structure representation of the molecules helps us understand the reaction. The equal sign tells us that the direction of this reaction is undefined. We can see that a methyl group of S adenosyl l-methionine is transferred to the nitrogen group of theobromine in order to produce caffeine. And like everywhere, throughout the rear website, all reaction participants are clickable and linked to a wealth of related information. By displaying the reaction participant table, we can get access to additional chemical information like charge, formula, smiles or in cheeky, and as always, links that help us navigate further. From this table, we can also learn that S adenosyl methionine is involved in hundreds of reactions. We can click on these numbers to browse the corresponding reactions. For example here, to see those reactions where S adenosyl methionine acts as a methyl donor. Going back to our original rear page, we look at the links to other resources. Each reaction in rear is organized as a quartet. In addition to the reaction with undefined direction, we can also identify directed reactions, left to right or forward, right to left or backward, or bidirectional. EC numbers are always linked to reactions with undefined directions. Keogh reactions, in contrast, are always linked to bidirectional reactions, while Metasike may have the four types of directionality. We can also see links to Uniprot KB, and in particular, we see that there is one protein associated with the left to right reaction. Clicking on the corresponding link, we are directed to the Uniprot entry for the protein from Robusta coffee, which catalyzes the methylation of ceobromine to produce caffeine. The function of Uniprot enzymes is frequently annotated with undefined directions, but when the information is available, the physiological direction is usually specified. Uniprot provides a prominent link back to the RIA website, and it is quite easy to navigate back and forth between the two resources. Do not hesitate to look at our other tutorials to get started, or to discover other functionalities of the RIA database and website. Thank you very much for your attention.