Benchmarking tools for the alignment of functional noncoding DNA.
Benchmarking tools for the alignment of functional noncoding DNA.
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DOI：
10.1186/1471-2105-5-6
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发表时间：
2004-01-21
影响因子：
3
通讯作者：
Eisen MB
中科院分区：
文献类型：
--
作者：
Pollard DA;Bergman CM;Stoye J;Celniker SE;Eisen MB
已经开发了许多工具来比对基因组序列。然而，它们在特定应用中的相对性能仍然很差。蛋白质编码序列的比对通常以从结构数据推断的“正确”比对为基准。对于非编码序列，缺乏这种独立的验证，模拟提供了一种有效的手段来生成“正确”的比对，与基准比对工具。使用从果蝇属估计的非编码序列进化速率，我们模拟了在不同模型下的分歧时间范围内的比对，包括点取代，插入/缺失事件，以及诸如在顺式调控区中发现的短块约束序列。然后，我们将由ROSE模拟平台的修改版本生成的“正确”比对与由八种成对比对工具（Avid、BlastZ、Chaos、ClustalW、DiAlign、Lagan、Needle和WABA）生成的模拟衍生序列的比对进行比较，以确定每个工具的现成性能。正如预期的那样，准确比对非编码序列的能力随着所有工具的分歧的增加而降低，并且在插入/缺失进化的存在下下降得更快。全局比对工具（Avid、ClustalW、Lagan和Needle）通常对整个非编码序列以及约束序列具有更高的灵敏度。局部工具（BlastZ、Chaos和WABA）由于覆盖不完全而具有较低的总体灵敏度，但是具有检测约束序列的高特异性以及它们比对的序列子集内的高灵敏度。DiAlign等工具可生成局部和全局输出，可对每个位点1.25-3.0个置换范围内的发散距离进行高灵敏度和特异性的约束序列比对。对于基因组特性与果蝇相似的物种，我们得出结论，一对最佳分歧的物种分析与高性能的比对工具可以产生准确和特定的功能受限的非编码序列的比对。进一步的算法开发，优化比对参数，和基准研究将是必要的，以提取最大的生物信息的功能非编码DNA的比对。
Numerous tools have been developed to align genomic sequences. However, their relative performance in specific applications remains poorly characterized. Alignments of protein-coding sequences typically have been benchmarked against "correct" alignments inferred from structural data. For noncoding sequences, where such independent validation is lacking, simulation provides an effective means to generate "correct" alignments with which to benchmark alignment tools. Using rates of noncoding sequence evolution estimated from the genus Drosophila, we simulated alignments over a range of divergence times under varying models incorporating point substitution, insertion/deletion events, and short blocks of constrained sequences such as those found in cis-regulatory regions. We then compared "correct" alignments generated by a modified version of the ROSE simulation platform to alignments of the simulated derived sequences produced by eight pairwise alignment tools (Avid, BlastZ, Chaos, ClustalW, DiAlign, Lagan, Needle, and WABA) to determine the off-the-shelf performance of each tool. As expected, the ability to align noncoding sequences accurately decreases with increasing divergence for all tools, and declines faster in the presence of insertion/deletion evolution. Global alignment tools (Avid, ClustalW, Lagan, and Needle) typically have higher sensitivity over entire noncoding sequences as well as in constrained sequences. Local tools (BlastZ, Chaos, and WABA) have lower overall sensitivity as a consequence of incomplete coverage, but have high specificity to detect constrained sequences as well as high sensitivity within the subset of sequences they align. Tools such as DiAlign, which generate both local and global outputs, produce alignments of constrained sequences with both high sensitivity and specificity for divergence distances in the range of 1.25–3.0 substitutions per site. For species with genomic properties similar to Drosophila, we conclude that a single pair of optimally diverged species analyzed with a high performance alignment tool can yield accurate and specific alignments of functionally constrained noncoding sequences. Further algorithm development, optimization of alignment parameters, and benchmarking studies will be necessary to extract the maximal biological information from alignments of functional noncoding DNA.
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影响因子：
12.3
作者：
Celniker SE;Wheeler DA;Kronmiller B;Carlson JW;Halpern A;Patel S;Adams M;Champe M;Dugan SP;Frise E;Hodgson A;George RA;Hoskins RA;Laverty T;Muzny DM;Nelson CR;Pacleb JM;Park S;Pfeiffer BD;Richards S;Sodergren EJ;Svirskas R;Tabor PE;Wan K;Stapleton M;Sutton GG;Venter C;Weinstock G;Scherer SE;Myers EW;Gibbs RA;Rubin GM
通讯作者：
Rubin GM
影响因子：
1.7
作者：
Holmes, I;Durbin, R
通讯作者：
Durbin, R
影响因子：
2.5
作者：
KATZ, RW
通讯作者：
KATZ, RW
影响因子：
3
作者：
Emberly, E;Rajewsky, N;Siggia, ED
通讯作者：
Siggia, ED
影响因子：
3.9
作者：
HASEGAWA, M;KISHINO, H;YANO, TA
通讯作者：
YANO, TA