Reliability and applications of statistical methods based on oligonucleotide frequencies in bacterial and archaeal genomes
Reliability and applications of statistical methods based on oligonucleotide frequencies in bacterial and archaeal genomes
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DOI：
10.1186/1471-2164-9-104
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发表时间：
2008-02-28
期刊：
影响因子：
4.4
通讯作者：
Ussery, David W.
中科院分区：
文献类型：
--
作者：
Bohlin, Jon;Skjerve, Eystein;Ussery, David W.
背景：越来越多的原核生物基因组测序包含了丰富的基因组数据，需要进行有效的分析。有一套统计工具可用于这种分析，但尚未充分探讨其优缺点。我们在这里关注的统计方法主要用于检查来自不同基因组的古细菌和细菌DNA之间的相似性。这些方法将观察到的固定大小寡核苷酸的基因组频率与预期值进行比较，预期值可以通过基因组核苷酸含量、较小的寡核苷酸频率或基于特定的统计分布来确定。这些统计方法的优点包括用从基因组内几乎任何地方取样的相对小的DNA片段测量系统发育关系，检测外源/保守DNA，以及同源性搜索。我们的目的是探索一些流行的方法，其中包括相对寡核苷酸频率（ROF），二至六核苷酸零阶马尔可夫方法（ZOM）和2。阶马尔可夫链方法（MCM）。对大DNA序列的远距离同源性搜索、外源/保守DNA的检测以及质粒-宿主相似性比较进行了测试。此外，通过比较真实的和随机的基因组DNA.Results的方法的可靠性进行了测试：我们的研究结果表明，最佳的方法是上下文相关。ROF最适合于远距离同源性搜索，而六核苷酸ZOM和MCM措施更可靠的措施，在同源性。当用于比较真实的基因组与具有相似%GC的人工构建的随机基因组时，二核苷酸ZOM方法产生高相关值，因此应谨慎使用。四核苷酸ZOM措施是一个很好的措施来检测水平转移的区域，当用于比较质粒和主机之间的系统发育关系，显着的相关性（R-2 = 0.4）被发现与基因组GC含量和染色体内homogeneity.Conclusion：统计方法检查是快速，易于实施，和强大的一些不同的应用程序，涉及基因组序列比较。然而，在所有的测试中，没有一个被检查的测量是上级的，因此统计方法的选择应该取决于手头的任务。
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 (R-2 = 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.