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Reliability and applications of statistical methods based on oligonucleotide frequencies in bacterial and archaeal genomes.

ABSTRACT: BACKGROUND: The increasing number of sequenced prokaryotic genomes contains a wealth of genomic data that needs to be effectively analysed. A set of statistical tools exists for such analysis, but their strengths and weaknesses have not been fully explored. The statistical methods we are concerned with here are mainly used to examine similarities between archaeal and bacterial DNA from different genomes. These methods compare observed genomic frequencies of fixed-sized oligonucleotides with expected values, which can be determined by genomic nucleotide content, smaller oligonucleotide frequencies, or be based on specific statistical distributions. Advantages with these statistical methods include measurements of phylogenetic relationship with relatively small pieces of DNA sampled from almost anywhere within genomes, detection of foreign/conserved DNA, and homology searches. Our aim was to explore the reliability and best suited applications for some popular methods, which include relative oligonucleotide frequencies (ROF), di- to hexanucleotide zero'th order Markov methods (ZOM) and 2.order Markov chain Method (MCM). Tests were performed on distant homology searches with large DNA sequences, detection of foreign/conserved DNA, and plasmid-host similarity comparisons. Additionally, the reliability of the methods was tested by comparing both real and random genomic DNA. RESULTS: Our findings show that the optimal method is context dependent. ROFs were best suited for distant homology searches, whilst the hexanucleotide ZOM and MCM measures were more reliable measures in terms of phylogeny. The dinucleotide ZOM method produced high correlation values when used to compare real genomes to an artificially constructed random genome with similar %GC, and should therefore be used with care. The tetranucleotide ZOM measure was a good measure to detect horizontally transferred regions, and when used to compare the phylogenetic relationships between plasmids and hosts, significant correlation (R2 = 0.4) was found with genomic GC content and intra-chromosomal homogeneity. CONCLUSION: The statistical methods examined are fast, easy to implement, and powerful for a number of different applications involving genomic sequence comparisons. However, none of the measures examined were superior in all tests, and therefore the choice of the statistical method should depend on the task at hand.

SUBMITTER: Bohlin J

PROVIDER: S-EPMC2289816 | biostudies-literature | 2008

REPOSITORIES: biostudies-literature

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Reliability and applications of statistical methods based on oligonucleotide frequencies in bacterial and archaeal genomes.

Bohlin Jon J Skjerve Eystein E Ussery David W DW

BMC genomics 20080228

<h4>Background</h4>The increasing number of sequenced prokaryotic genomes contains a wealth of genomic data that needs to be effectively analysed. A set of statistical tools exists for such analysis, but their strengths and weaknesses have not been fully explored. The statistical methods we are concerned with here are mainly used to examine similarities between archaeal and bacterial DNA from different genomes. These methods compare observed genomic frequencies of fixed-sized oligonucleotides wi ...[more]

PMID: 18307761

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Project description:During the long history of biological evolution, genome structures have undergone enormous changes. Nevertheless, some traits or vestiges of the primordial genome (defined as the most primitive nucleic acid genome for life on earth in this paper) may remain in modern genetic systems. It is of great importance to find these traits or vestiges for the study of the origin and evolution of genomes. As the shorter is a sequence, the less probable it would be modified during genome evolution. And if mutated, it would be easier to reappear at the same site or another site. Consequently, the genomic frequencies of very short nucleotide sequences, such as dinucleotides, would have considerable chances to be conserved during billions of years of evolution. Prokaryotic genomes are very diverse and with a wide range of GC content. Therefore, in order to find traits or vestiges of the primordial genome remained in modern genetic systems, we have studied the characteristics of dinucleotide frequencies across bacterial and archaeal genomes. We analyzed the dinucleotide frequency patterns of the whole-genome sequences from more than 1300 prokaryotic species (bacterial and archaeal genomes available as of December 2012). The results show that the frequencies of the dinucleotides AC, AG, CA, CT, GA, GT, TC, and TG are well-conserved across various genomes, while the frequencies of other dinucleotides vary considerably among species. The dinucleotide frequency conservation/variation pattern seems to correlate with the distributions of dinucleotides throughout a genome and across genomes. Further analysis indicates that the phenomenon would be determined by strand symmetry of genomic sequences (the second parity rule) and GC content variations among genomes. We discussed some possible origins of strand symmetry. And we propose that the phenomenon of frequency conservation of some dinucleotides may provide insights into the genomic composition of the primordial genetic system.

Dataset Information

Reliability and applications of statistical methods based on oligonucleotide frequencies in bacterial and archaeal genomes.

Publications

Reliability and applications of statistical methods based on oligonucleotide frequencies in bacterial and archaeal genomes.

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