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Computational identification of promoters and first exons in the human genome

A Corrigendum to this article was published on 01 November 2002

Abstract

The identification of promoters and first exons has been one of the most difficult problems in gene-finding. We present a set of discriminant functions that can recognize structural and compositional features such as CpG islands, promoter regions and first splice-donor sites. We explain the implementation of the discriminant functions into a decision tree that constitutes a new program called FirstEF. By using different models to predict CpG-related and non-CpG-related first exons, we showed by cross-validation that the program could predict 86% of the first exons with 17% false positives. We also demonstrated the prediction accuracy of FirstEF at the genome level by applying it to the finished sequences of human chromosomes 21 and 22 as well as by comparing the predictions with the locations of the experimentally verified first exons. Finally, we present the analysis of the predicted first exons for all of the 24 chromosomes of the human genome.

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Figure 1: Histogram of CpG scores for all of the 2,139 first exons of our first-exon database.
Figure 2: Histogram of the relative distance between the 5′ end of the CpG window and the splice-donor site for CpG-related first exons.
Figure 3: Histograms of the relative distance between the 5′ end of the predicted first exon (TSS) and the annotated translation start codon (ATG) for human chromosome 21 (Fig. 3a) and human chromosome 22 (Fig. 3b).

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Acknowledgements

This work was supported by grants to M.Q.Z. from the National Institutes of Health, and I.G. is also supported by a CSHL Association fellowship. We thank G. Chen for setting up the web interface to FirstEF, as well as N. Banerjee, K. Hermann, H. Herzel, M. Hoffman, D. Holste, W. Li, F. Lillo, M. Ronemus, R. Sachidanandam, K. Rateitschak, A. Schmitt and Z. Xuan for valuable discussions and comments on the manuscript.

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Correspondence to Michael Q. Zhang.

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Davuluri, R., Grosse, I. & Zhang, M. Computational identification of promoters and first exons in the human genome. Nat Genet 29, 412–417 (2001). https://doi.org/10.1038/ng780

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