Biomedical subjects

P J Greaney

Publications and source records attributed to P J Greaney.

3 recordsLinked to original sources

PubMed1996

Statistical comparison of established T-cell epitope predictors against a large database of human and murine antigens.

Identification of T-cell epitopes within a protein antigen is an important tool in vaccine design. The T-cell epitope prediction schemes often are exploited by workers but have proved unreliable in comparison with experimental techniques. We compared published T-cell epitope predictors against two databases of human and murine T-cell epitopes. Each predictor was assessed against random cyclic permutations of epitopes in order to determine significance. Predictor performance was expressed in terms of two parameters, specificity and sensitivity. Specificity is an expression of the quality of predictions, whereas sensitivity is an expression of the quantity of epitopes predicted. Against the human data set, the strip-of-hydrophobic helix algorithm [Stille et al., Molec. Immun. 24, 1021-1027 (1987)] was the only significant predictor (p < 0.05), whereas against murine data only, the Roth2 pattern [Rothbard and Taylor, EMBO J. 7, 93-100 (1988)] was significant (p < 0.05). Not only were the majority of algorithms no better than random against both data sets, against the murine data two schemes were significant (p < 0.05) anti-predictors. This report indicates which predictors are relevant statistically and is the first to describe anti-predictors which can themselves be useful in the identification of T-cell epitopes.

Algorithms↗

PubMed1994

A method for rapidly assessing and refining simple solvent treatments in molecular modelling. Example studies on the antigen-combining loop H2 from FAB fragment McPC603.

Different simple solvent models have been implemented in an extended simulated annealing process (ESAP), developed by Higo et al. [(1992) Biopolymers, 32, 33-43] and proven to be able to predict ab initio the conformation of the antigen-combining loop H2 from FAB McPC603. The rationale used here provides a useful new method for testing solvent models in general. The different solvent models comprise a high dielectric constant, a screened coulomb potential, a dummy water model and a statistical continuum treatment of the solvent effect in which the reaction field and the solvent accessible area is accounted for. To assess the effect of the solvent, we tested the ability of simulations to retain the experimental conformation of loop H2. We compared the different structures obtained at the end of the annealing process in terms of root mean square deviation (r.m.s.d.), for both the backbone and for all atoms, root mean square (r.m.s.) fluctuation, solvent accessible surface area (ASA), hydrogen bonding network and phi-psi plot distribution. The relationship between the r.m.s.d. and the internal energy of a structure is also evaluated in terms of precision and another possible method for obtaining the best conformation is discussed. The accuracy of modelling the coarse effect of the solvent and the similarities of the resulting structures with respect to the X-ray reference structure are examined. The possible choice of one of these solvent models in the structure determination of an unknown loop structure is discussed.

Algorithms↗

PubMed1992

Natural sequence code representations for compression and rapid searching of human-genome style databases.

Numeric descriptions ('bio-informatic descriptions') of amino acid residues have been developed which will be of value whenever the quality and quantity of information in very large (i.e. 'human genome style') gene and protein sequences is to be compared or manipulated. These codes are as natural as possible by our criteria (the same principles could be used in revision of the criteria). In particular, in storing and searching large amounts of sequence data, natural codes--which relate to the properties of amino acids--can be combined with existing fast-search algorithms but introduce several advantages. The code can be assigned such that sub-selection of bits leads to compressed databases with residues defined less specifically, by classes of properties. The most compressed representation leads to the specification of a residue as polar or non-polar, while the most extended representation used at present also allows specification of, for example, glyco-asparagine and phosphoserine. Preliminary studies on both a supercomputer and smaller machines suggest a 'worst-case' speeding of approximately 4.5-fold. For more intelligent searching, coding extensions mixed with the basic sequence data give the sequence data some of the character of a computer program.

Amino Acid Sequence↗