TreeDet: a web server to explore sequence space

Abstract

The TreeDet (Tree Determinant) Server is the first release of a system designed to integrate results from methods that predict functional sites in protein families. These methods take into account the relation between sequence conservation and evolutionary importance. TreeDet fully analyses the space of protein sequences in either user-uploaded or automatically generated multiple sequence alignments. The methods implemented in the server represent three main classes of methods for the detection of family-dependent conserved positions, a tree-based method, a correlation based method and a method that employs a principal component analyses coupled to a cluster algorithm. An additional method is provided to highlight the reliability of the position in the alignments. The server is available at http://www.pdg.cnb.uam.es/servers/treedet.

Figure 1

TreeDet results page. This section provides a table with predicted positions associated to an input alignment. By clicking on the numbered positions the alignment moves towards these positions. The sequences in the alignment are re-ordered according either FASS or S-method and the resulting sequence clusters are highlighted in various shades of cyan. The scroll bar above the alignment includes the query sequence. The residues are highlighted by the optimal score from SQUARE, and indication of the conservation of each position within the broader sequence family. The predicted positions are highlighted according to Taylor's schema (19). For instance, the position 37 predicted by FASS and MB is critical for functional specificity (11). Additional XML files are provided to easy automated processing of the files. If a method does not provide results it is also indicated.

Figure 2

SQUARE results output. The main results page provides a link to SQUARE. The multiple alignment shows the reliability of the alignment and detailed graphics show the score distribution along each sequence of the alignment.

Figure 3

Overall reliability. This figure shows the reliability of the alignment from which the tree determinants for the sequence RAS3_DROME have been predicted. As seen from the darker colours in the figure, the alignment from which the position 37 (arrowhead) has been predicted by FASS and MB is highly reliable according to SQUARE. The regions in both alignments are marked with boxes.