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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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Entropy rate, using the Lempel-Ziv 77 algorithm, for the coding sequence (red) and the genomic sequence for chromosome 20 (green), as a function of the length of the sequence analyzed. The entropy calculation converges after 10 million bases.
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Figure 5: Entropy rate, using the Lempel-Ziv 77 algorithm, for the coding sequence (red) and the genomic sequence for chromosome 20 (green), as a function of the length of the sequence analyzed. The entropy calculation converges after 10 million bases.

Mentions: Previous studies have examined the entropy, or information content, within regions of a genome [6-8]. We calculated the information content of each human chromosome. This facilitates comparisons between chromosomes. We used the Lempel-Ziv 77 algorithm to estimate the entropy rate of both coding sequences and whole genomic sequences for the human genome [17]. Coding sequences have a higher entropy rate (information content) than genomic sequences (Figure 5). Note that the highly repetitive regions of telomeres and centromeres are generally coded as non-specific bases ("N") in the human genome and so are excluded from our calculations. Entropy was calculated from either the entire chromosome, for chromosomes < 130 Mb, or the first 130 Mb of longer chromosomes. This is sufficient to generate stable estimates of the entropy (Figure 5). Figure 6 shows both the entropy and the percent of the chromosome filled by coding regions for each human chromosome.


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)

Entropy rate, using the Lempel-Ziv 77 algorithm, for the coding sequence (red) and the genomic sequence for chromosome 20 (green), as a function of the length of the sequence analyzed. The entropy calculation converges after 10 million bases.
© Copyright Policy - open-access
Related In: Results  -  Collection

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

Figure 5: Entropy rate, using the Lempel-Ziv 77 algorithm, for the coding sequence (red) and the genomic sequence for chromosome 20 (green), as a function of the length of the sequence analyzed. The entropy calculation converges after 10 million bases.
Mentions: Previous studies have examined the entropy, or information content, within regions of a genome [6-8]. We calculated the information content of each human chromosome. This facilitates comparisons between chromosomes. We used the Lempel-Ziv 77 algorithm to estimate the entropy rate of both coding sequences and whole genomic sequences for the human genome [17]. Coding sequences have a higher entropy rate (information content) than genomic sequences (Figure 5). Note that the highly repetitive regions of telomeres and centromeres are generally coded as non-specific bases ("N") in the human genome and so are excluded from our calculations. Entropy was calculated from either the entire chromosome, for chromosomes < 130 Mb, or the first 130 Mb of longer chromosomes. This is sufficient to generate stable estimates of the entropy (Figure 5). Figure 6 shows both the entropy and the percent of the chromosome filled by coding regions for each human chromosome.

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