Positional characterisation of false positives from computational prediction of human splice sites - PubMed (original) (raw)

Comparative Study

Positional characterisation of false positives from computational prediction of human splice sites

T A Thanaraj. Nucleic Acids Res. 2000.

Abstract

The performance of computational tools that can predict human splice sites are reviewed using a test set of EST-confirmed splice sites. The programs (namely HMMgene, NetGene2, HSPL, NNSPLICE, SpliceView and GeneID-3) differ from one another in the degree of discriminatory information used for prediction. The results indicate that, as expected, HMMgene and NetGene2 (which use global as well as local coding information and splice signals) followed by HSPL (which uses local coding information and splice signals) performed better than the other three programs (which use only splice signals). For the former three programs, one in every three false positive splice sites was predicted in the vicinity of true splice sites while only one in every 12 was expected to occur in such a region by chance. The persistence of this observation for programs (namely FEXH, GRAIL2, MZEF, GeneID-3, HMMgene and GENSCAN) that can predict all the potential exons (including optimal and sub-optimal) was assessed. In a high proportion (>50%) of the partially correct predicted exons, the incorrect exon ends were located in the vicinity of the real splice sites. Analysis of the distribution of proximal false positives indicated that the splice signals used by the algorithms are not strong enough to discriminate particularly those false predictions that occur within +/- 25 nt around the real sites. It is therefore suggested that specialised statistics that can discriminate real splice sites from proximal false positives be incorporated in gene prediction programs.

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Figures

Figure 1

Figure 1

(a) Performance of donor site prediction programs in terms of specificity and sensitivity (shown by solid lines). Also shown are percentage of false positive donor sites that are proximal (shown by dashed lines). (b) Performance of acceptor site prediction programs in terms of specificity and sensitivity (shown by solid lines). Also shown are percentage of false positive acceptor sites that are proximal (shown by dashed lines).

Figure 1

Figure 1

(a) Performance of donor site prediction programs in terms of specificity and sensitivity (shown by solid lines). Also shown are percentage of false positive donor sites that are proximal (shown by dashed lines). (b) Performance of acceptor site prediction programs in terms of specificity and sensitivity (shown by solid lines). Also shown are percentage of false positive acceptor sites that are proximal (shown by dashed lines).

Figure 2

Figure 2

(a) Proportion of false donor sites with a score ≥ that of real donor sites. (b) Proportion of false acceptor sites with a score ≥ that of real acceptor sites.

Figure 2

Figure 2

(a) Proportion of false donor sites with a score ≥ that of real donor sites. (b) Proportion of false acceptor sites with a score ≥ that of real acceptor sites.

Figure 3

Figure 3

(a) Performance of donor site prediction programs in terms of corrected specificity and sensitivity (shown by solid lines). Also shown are corrected percentage of false positive donor sites that are proximal (shown by dashed lines). Only those false positive donor sites with a score ≥ that of real donor sites were considered. (b) Performance of acceptor site prediction programs in terms of corrected specificity and sensitivity (shown by solid lines). Also shown are the corrected percentage of false positive acceptor sites that are proximal (shown by dashed lines). Only those false positive donor sites with a score ≥ that of real acceptor sites were considered.

Figure 3

Figure 3

(a) Performance of donor site prediction programs in terms of corrected specificity and sensitivity (shown by solid lines). Also shown are corrected percentage of false positive donor sites that are proximal (shown by dashed lines). Only those false positive donor sites with a score ≥ that of real donor sites were considered. (b) Performance of acceptor site prediction programs in terms of corrected specificity and sensitivity (shown by solid lines). Also shown are the corrected percentage of false positive acceptor sites that are proximal (shown by dashed lines). Only those false positive donor sites with a score ≥ that of real acceptor sites were considered.

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