JPred : a consensus secondary structure prediction server

Summary: An interactive protein secondary structure prediction Internet server is presented. The server allows a single sequence or multiple alignment to be submitted, and returns predictions from six secondary structure prediction algorithms that exploit evolutionary information from multiple sequences. A consensus prediction is also returned which improves the average Q3 accuracy of prediction by 1% to 72.9%. The server simplifies the use of current prediction algorithms and allows conservation patterns important to structure and function to be identified . Availability: http://barton.ebi.ac.uk/servers/jpred.html Contact: geoff@ebi.ac.uk When predicting the secondary structure of a protein ‘blind’, without knowledge of the answer, it is useful to exploit the features of all available prediction algorithms rather than rely on one. Combination of methods has been applied successfully in a number of accurate predictions of protein secondary structure (e.g. see Edwards and Perkins, 1996; Crawford et al., 1994; Russell et al., 1992; Livingston and Barton, 1994, 1996; Russell and Barton, 1993). Unfortunately, combining prediction methods on a large scale is complicated by the fact that prediction programs have very different input requirements and output formats. In order to perform a recent large-scale comparative analysis of secondary structure prediction algorithms (Cuff and Barton, 1998), we developed flexible software to standardise the input and output requirements of six prediction algorithms. In this paper we describe a development of this work to provide the fully automatic JPred WWW server for multiple secondary structure prediction. The server accepts two input types, a family of aligned protein sequences or a single protein sequence. If a single sequence is submitted, an automatic process creates a multiple sequence alignment, prior to prediction (Cuff and Barton, 1998). Six different prediction methods (DSC (King and Sternberg, 1996), PHD (Rost and Sander, 1993), NNSSP (Salamov and Solovyev, 1995), PREDATOR (Frishman and Argos, 1997), ZPRED (Zvelebil et al., 1987) and MULPRED (Barton, 1988, unpublished)) are then run, and the results from each method are combined into a simple file format. The NNSSP, DSC, PREDATOR, MULPRED, ZPRED and PHD methods were chosen as representatives of current state-of-the-art secondary structure prediction methods that exploit the evolutionary information from multiple sequences. Each derives its prediction using a different heuristic, based upon nearest neighbours (NNSSP), jury decision neural networks (PHD), linear discrimination (DSC), consensus single sequence method combination (MULPRED), hydrogen bonding propensities (PREDATOR), or conservation number weighted prediction (ZPRED). The predictions and corresponding sequence alignment are rendered in coloured HTML, Java (Clamp et al., 1998) and Postscript. The predictions are coloured and aligned with their corresponding family of sequences. Physico-chemical properties, solvent accessibility, prediction reliability and conservation number values (Zvelebil et al., 1987) for each amino acid are included in the output. The original ASCII text data from each of the prediction methods can also be downloaded. For example, BLAST results (Altschul et al., 1990), MSF and HSSP (Sander and Schneider, 1991) format alignments, pair comparison files and so on. The text based MULPRED output is of particular interest as it is a combination of different single sequence prediction methods (Garnier et al., 1978; Chou and Fasman, 1974; Lim, 1974; Rose, 1978; Wilmot and Thornton, 1988). While the automatic consensus within the MULPRED program is not as accurate as current methods (Cuff and Barton, 1998), the profile based output, when combined with the modern algorithms is helpful for human interpretation of the prediction. A consensus prediction based upon a simple majority wins combination of NNSSP, DSC, PREDATOR and PHD is provided by the JPred server. If there is a tie, the prediction from PHD is used. In our independent test this approach gave the 0/0