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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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The percentage of all possible n-mers (coverage) that appear in H. sapien, M. musculus, D. melanogaster, C. elegans, A. thaliana, S. cerevisiae, E. coli k12, theoretical and pseudo-human genomes. Theo-human is the maximum coverage a human-length genome could achieve if every n-mer in its genome was unique. The pseudo-human (pseudo-hs) genome is a random genome generated with the same length and dinucleotide frequencies of the human genome. The space coverage of each genome listed above is plotted against the length of the oligomer analyzed, ranging from 1 to 20.
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Figure 1: The percentage of all possible n-mers (coverage) that appear in H. sapien, M. musculus, D. melanogaster, C. elegans, A. thaliana, S. cerevisiae, E. coli k12, theoretical and pseudo-human genomes. Theo-human is the maximum coverage a human-length genome could achieve if every n-mer in its genome was unique. The pseudo-human (pseudo-hs) genome is a random genome generated with the same length and dinucleotide frequencies of the human genome. The space coverage of each genome listed above is plotted against the length of the oligomer analyzed, ranging from 1 to 20.

Mentions: We randomly generated 5 sets of 100,000 probes for each oligo length n, and then determined the proportion of those n-mers present in the genomes of Homo sapiens, Mus musculus, Drosophila melanogaster, Caenorhabditis elegans, Arabidopsis thaliana, Saccharomyces cerevisiae, and Escherichia coli k12. The n-mer space coverage for each genome is plotted against oligo length n in Figure 1 (See additional file 1 for the data). The E. coli genome includes all 8-mers, and less than 0.21% of all 16-mers. In contrast, the human genome includes all 11-mers and less than 0.38% of all 20-mers. Of course, n-mer space coverage reflects genome size to some extent. For example, the human genome has a much higher coverage than the yeast genome for every oligo length. The 7 genomes that we investigated in this study differ the most in their coverage for 13-mer space, ranging from 11.4% coverage for E. coli to 96% coverage for human and mouse. For comparison, we also generated a random "pseudo" human genome with the same length and dinucleotide frequencies (see Appendix for a formal analysis of the expected number of n-mers in this pseudo-human genome). The fact that the true human genome has less coverage of n-mer space than the pseudo-human genome (Figure 1) shows that there are more repeated n-mers in the human genome than one would expect by chance.


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)

The percentage of all possible n-mers (coverage) that appear in H. sapien, M. musculus, D. melanogaster, C. elegans, A. thaliana, S. cerevisiae, E. coli k12, theoretical and pseudo-human genomes. Theo-human is the maximum coverage a human-length genome could achieve if every n-mer in its genome was unique. The pseudo-human (pseudo-hs) genome is a random genome generated with the same length and dinucleotide frequencies of the human genome. The space coverage of each genome listed above is plotted against the length of the oligomer analyzed, ranging from 1 to 20.
© Copyright Policy - open-access
Related In: Results  -  Collection

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

Figure 1: The percentage of all possible n-mers (coverage) that appear in H. sapien, M. musculus, D. melanogaster, C. elegans, A. thaliana, S. cerevisiae, E. coli k12, theoretical and pseudo-human genomes. Theo-human is the maximum coverage a human-length genome could achieve if every n-mer in its genome was unique. The pseudo-human (pseudo-hs) genome is a random genome generated with the same length and dinucleotide frequencies of the human genome. The space coverage of each genome listed above is plotted against the length of the oligomer analyzed, ranging from 1 to 20.
Mentions: We randomly generated 5 sets of 100,000 probes for each oligo length n, and then determined the proportion of those n-mers present in the genomes of Homo sapiens, Mus musculus, Drosophila melanogaster, Caenorhabditis elegans, Arabidopsis thaliana, Saccharomyces cerevisiae, and Escherichia coli k12. The n-mer space coverage for each genome is plotted against oligo length n in Figure 1 (See additional file 1 for the data). The E. coli genome includes all 8-mers, and less than 0.21% of all 16-mers. In contrast, the human genome includes all 11-mers and less than 0.38% of all 20-mers. Of course, n-mer space coverage reflects genome size to some extent. For example, the human genome has a much higher coverage than the yeast genome for every oligo length. The 7 genomes that we investigated in this study differ the most in their coverage for 13-mer space, ranging from 11.4% coverage for E. coli to 96% coverage for human and mouse. For comparison, we also generated a random "pseudo" human genome with the same length and dinucleotide frequencies (see Appendix for a formal analysis of the expected number of n-mers in this pseudo-human genome). The fact that the true human genome has less coverage of n-mer space than the pseudo-human genome (Figure 1) shows that there are more repeated n-mers in the human genome than one would expect by chance.

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