W228 Nucleic Acids Research, 2006, Vol. 34, Web Server issue Figure 2. Target page with Rank function activated. The menu area (on the left) shows a summary of the results returned by the Select function. The work area (on the right) allows users to specify which data to display for the selected targets, and how to rank those targets by specifying the priority of each annotation. Users can choose to view the prioritized target list as a Web page (by clicking the HTML button) or, alternatively, as a tabbed text file (by clicking the TEXT button). In this case, 49 targets were selected with the criteria specified in Figure 1. The target list is to be ranked with decreasing coverage by NRDB database (i.e. proteins with more of their length annotated as similar to a protein in the NRDB database have higher priority) and a number of protein physicochemical properties are to be displayed along with the default attributes (off the screen in this screenshot) (see Figure 3 for resulting page). by characteristic enables users to investigate the results of a particular set of calculations for that dataset. This includes global statistics for gene expression predictions, structural and functional annotations, prevalence assignments, trans- membrane and non-globular regions predictions, as well as physicochemical properties. Within the View page, users can also search each subset using the Search function. It allows users to ﬁnd proteins using the resource’s own identi- ﬁer, as well as other identiﬁers (GenBank accession no.) and names (sequencing center naming), as provided by the sequence input ﬁles. Target The Target page enables users to select and prioritize targets. The Select function is used to specify the datasets to target, which gene and protein properties the targets should possess, and what parameters and thresholds should be employed in the selection (Figure 1). All annotations established through the annotation pipeline can be employed as selection parameters. Upon selecting targets, users are presented with the Rank function, which enables them to perform target prioritization (Figure 2). This function also allows users to choose the format and layout of the target list, which is ﬁnally presented to them (Figure 3). APPLICATION sgTarget has underpinned the selection of targets for our labor- atory’s collaboration in the Plasmodium Functional Genomics Initiative. The resource was employed to annotate the genome of Plasmodium falciparum, the organism that causes the most fatal form of human malaria (Figure 4). This enabled the generation of a target list by reﬁning the selection choices to consider parameters selected by researchers in the group. The initial list of 73 targets consists of malaria proteins encoded by single exon genes with GC contents higher than 30%, no transmembrane regions and no long non-globular hydrophilic regions. GC content and intron number are the most selective of the parameters, together reducing the number of possible targets by 98%. These selection criteria were cho- sen to identify proteins likely to express in E.coli, and initial results obtained by the group indicate that the target list has been successful on those terms (13). Thus far, the group have initiated work on 10 of these targets, successfully cloned and expressed 8, puriﬁed 6, of which 1 is in crystallization trials [and has also been shown to be crucial for the parasite’s invasion of human red blood cells, (14)] and 3 have already yielded high-resolution structures (15,16) and Boucher, I., Brzozowski, A.M., Brannigan, J.A., Schnick, C., Smith, D., Kyes, S. and Wilkinson, A.J., manuscript in preparation.