First pass annotation of promoters on human chromosome 22

Abstract

The publication of the first almost complete sequence of a human chromosome (chromosome 22) is a major milestone in human genomics. Together with the sequence, an excellent annotation of genes was published which certainly will serve as an information resource for numerous future projects. We noted that the annotation did not cover regulatory regions; in particular, no promoter annotation has been provided. Here we present an analysis of the complete published chromosome 22 sequence for promoters. A recent breakthrough in specific in silico prediction of promoter regions enabled us to attempt large-scale prediction of promoter regions on chromosome 22. Scanning of sequence databases revealed only 20 experimentally verified promoters, of which 10 were correctly predicted by our approach. Nearly 40% of our 465 predicted promoter regions are supported by the currently available gene annotation. Promoter finding also provides a biologically meaningful method for "chromosomal scaffolding", by which long genomic sequences can be divided into segments starting with a gene. As one example, the combination of promoter region prediction with exon/intron structure predictions greatly enhances the specificity of de novo gene finding. The present study demonstrates that it is possible to identify promoters in silico on the chromosomal level with sufficient reliability for experimental planning and indicates that a wealth of information about regulatory regions can be extracted from current large-scale (megabase) sequencing projects. Results are available on-line at http://genomatix.gsf.de/chr22/.

Figure 1

Correlation analysis of PromoterInspector promoter regions with annotated gene starts on chromosome 22 (+ strand shown). The y-axis indicates the total number of matches found in relative distance to the annotated gene start. Values on the x-axis with a negative sign mark distances to promoter regions which are located upstream of an annotated gene start, while positive values mark distances to promoter regions which are located downstream from an annotated gene start. The column at distance value 0 marks the number of promoter regions which overlap with an annotated gene start. The range accepted as tolerance is highlighted in black. (A), known and related genes as defined by Dunham et al. (1999). (B), predicted genes as defined by Dunham et al. (1999).

Figure 1

Correlation analysis of PromoterInspector promoter regions with annotated gene starts on chromosome 22 (+ strand shown). The y-axis indicates the total number of matches found in relative distance to the annotated gene start. Values on the x-axis with a negative sign mark distances to promoter regions which are located upstream of an annotated gene start, while positive values mark distances to promoter regions which are located downstream from an annotated gene start. The column at distance value 0 marks the number of promoter regions which overlap with an annotated gene start. The range accepted as tolerance is highlighted in black. (A), known and related genes as defined by Dunham et al. (1999). (B), predicted genes as defined by Dunham et al. (1999).