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Sequence space coverage, entropy of genomes and the potential to detect non-human DNA in human samples.

Liu Z, Venkatesh SS, Maley CC - BMC Genomics (2008)

Bottom Line: The human genome is significantly more compact in sequence space than a random genome.The entropy of coding regions in the human genome is significantly higher than non-coding regions and chromosomes.This information may be used to detect novel microbes in human tissues.

View Article: PubMed Central - HTML - PubMed

Affiliation: Genomics and Computational Biology Graduate Group, School of Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA. zhandong@mail.med.upenn.edu

ABSTRACT

Background: Genomes store information for building and maintaining organisms. Complete sequencing of many genomes provides the opportunity to study and compare global information properties of those genomes.

Results: We have analyzed aspects of the information content of Homo sapiens, Mus musculus, Drosophila melanogaster, Caenorhabditis elegans, Arabidopsis thaliana, Saccharomyces cerevisiae, and Escherichia coli (K-12) genomes. Virtually all possible (> 98%) 12 bp oligomers appear in vertebrate genomes while < 2% of 19 bp oligomers are present. Other species showed different ranges of > 98% to < 2% of possible oligomers in D. melanogaster (12-17 bp), C. elegans (11-17 bp), A. thaliana (11-17 bp), S. cerevisiae (10-16 bp) and E. coli (9-15 bp). Frequencies of unique oligomers in the genomes follow similar patterns. We identified a set of 2.6 M 15-mers that are more than 1 nucleotide different from all 15-mers in the human genome and so could be used as probes to detect microbes in human samples. In a human sample, these probes would detect 100% of the 433 currently fully sequenced prokaryotes and 75% of the 3065 fully sequenced viruses. The human genome is significantly more compact in sequence space than a random genome. We identified the most frequent 5- to 20-mers in the human genome, which may prove useful as PCR primers. We also identified a bacterium, Anaeromyxobacter dehalogenans, which has an exceptionally low diversity of oligomers given the size of its genome and its GC content. The entropy of coding regions in the human genome is significantly higher than non-coding regions and chromosomes. However chromosomes 1, 2, 9, 12 and 14 have a relatively high proportion of coding DNA without high entropy, and chromosome 20 is the opposite with a low frequency of coding regions but relatively high entropy.

Conclusion: Measures of the frequency of oligomers are useful for designing PCR assays and for identifying chromosomes and organisms with hidden structure that had not been previously recognized. This information may be used to detect novel microbes in human tissues.

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(a) Coverage of 10-mer sequence space as a function of genome size in 433 fully sequenced microbial genomes. The legend for the color-coding of GC content appears on the right. Smaller genomes have lower GC content. Anaeromyxobacter dehalogenans is an outlier with unusually low coverage for its genome size and GC content (outside of the 99.9% predicted interval). (b) A histogram for the proportion of the 10-mer sequence space covered by each of the 433 fully sequenced microbial genomes.
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Figure 2: (a) Coverage of 10-mer sequence space as a function of genome size in 433 fully sequenced microbial genomes. The legend for the color-coding of GC content appears on the right. Smaller genomes have lower GC content. Anaeromyxobacter dehalogenans is an outlier with unusually low coverage for its genome size and GC content (outside of the 99.9% predicted interval). (b) A histogram for the proportion of the 10-mer sequence space covered by each of the 433 fully sequenced microbial genomes.

Mentions: The coverage analysis of genomes can be used to analyze the complexity of any fully sequenced genome. We applied this analysis to 433 fully sequenced microbial genomes (Figure 2, see additional file 2 for the species, coverage, GC content and genome sizes). A multivariate regression of log genome size and deviation of GC content from 0.5 frequency, on 10-mer sequence space coverage, shows that variation in coverage can almost entirely be explained by genome size and GC content (adjusted R2 = 0.92, p < 0.01). However, Anaeromyxobacter dehalogenans is an outlier with lower coverage than would be predicted by the model (actual coverage = 0.406, predicted coverage = 0.563, 99.9% predicted interval: 0.412–0.713). In addition, we confirmed the significant association between log genome size and GC content such that organisms with smaller genomes have lower GC content (Figure 2, linear regression p < 0.001) [16].


Sequence space coverage, entropy of genomes and the potential to detect non-human DNA in human samples.

Liu Z, Venkatesh SS, Maley CC - BMC Genomics (2008)

(a) Coverage of 10-mer sequence space as a function of genome size in 433 fully sequenced microbial genomes. The legend for the color-coding of GC content appears on the right. Smaller genomes have lower GC content. Anaeromyxobacter dehalogenans is an outlier with unusually low coverage for its genome size and GC content (outside of the 99.9% predicted interval). (b) A histogram for the proportion of the 10-mer sequence space covered by each of the 433 fully sequenced microbial genomes.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC2628393&req=5

Figure 2: (a) Coverage of 10-mer sequence space as a function of genome size in 433 fully sequenced microbial genomes. The legend for the color-coding of GC content appears on the right. Smaller genomes have lower GC content. Anaeromyxobacter dehalogenans is an outlier with unusually low coverage for its genome size and GC content (outside of the 99.9% predicted interval). (b) A histogram for the proportion of the 10-mer sequence space covered by each of the 433 fully sequenced microbial genomes.
Mentions: The coverage analysis of genomes can be used to analyze the complexity of any fully sequenced genome. We applied this analysis to 433 fully sequenced microbial genomes (Figure 2, see additional file 2 for the species, coverage, GC content and genome sizes). A multivariate regression of log genome size and deviation of GC content from 0.5 frequency, on 10-mer sequence space coverage, shows that variation in coverage can almost entirely be explained by genome size and GC content (adjusted R2 = 0.92, p < 0.01). However, Anaeromyxobacter dehalogenans is an outlier with lower coverage than would be predicted by the model (actual coverage = 0.406, predicted coverage = 0.563, 99.9% predicted interval: 0.412–0.713). In addition, we confirmed the significant association between log genome size and GC content such that organisms with smaller genomes have lower GC content (Figure 2, linear regression p < 0.001) [16].

Bottom Line: The human genome is significantly more compact in sequence space than a random genome.The entropy of coding regions in the human genome is significantly higher than non-coding regions and chromosomes.This information may be used to detect novel microbes in human tissues.

View Article: PubMed Central - HTML - PubMed

Affiliation: Genomics and Computational Biology Graduate Group, School of Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA. zhandong@mail.med.upenn.edu

ABSTRACT

Background: Genomes store information for building and maintaining organisms. Complete sequencing of many genomes provides the opportunity to study and compare global information properties of those genomes.

Results: We have analyzed aspects of the information content of Homo sapiens, Mus musculus, Drosophila melanogaster, Caenorhabditis elegans, Arabidopsis thaliana, Saccharomyces cerevisiae, and Escherichia coli (K-12) genomes. Virtually all possible (> 98%) 12 bp oligomers appear in vertebrate genomes while < 2% of 19 bp oligomers are present. Other species showed different ranges of > 98% to < 2% of possible oligomers in D. melanogaster (12-17 bp), C. elegans (11-17 bp), A. thaliana (11-17 bp), S. cerevisiae (10-16 bp) and E. coli (9-15 bp). Frequencies of unique oligomers in the genomes follow similar patterns. We identified a set of 2.6 M 15-mers that are more than 1 nucleotide different from all 15-mers in the human genome and so could be used as probes to detect microbes in human samples. In a human sample, these probes would detect 100% of the 433 currently fully sequenced prokaryotes and 75% of the 3065 fully sequenced viruses. The human genome is significantly more compact in sequence space than a random genome. We identified the most frequent 5- to 20-mers in the human genome, which may prove useful as PCR primers. We also identified a bacterium, Anaeromyxobacter dehalogenans, which has an exceptionally low diversity of oligomers given the size of its genome and its GC content. The entropy of coding regions in the human genome is significantly higher than non-coding regions and chromosomes. However chromosomes 1, 2, 9, 12 and 14 have a relatively high proportion of coding DNA without high entropy, and chromosome 20 is the opposite with a low frequency of coding regions but relatively high entropy.

Conclusion: Measures of the frequency of oligomers are useful for designing PCR assays and for identifying chromosomes and organisms with hidden structure that had not been previously recognized. This information may be used to detect novel microbes in human tissues.

Show MeSH
Related in: MedlinePlus