Accurate estimation of short read mapping quality for next-generation genome sequencing.
Accurate estimation of short read mapping quality for next-generation genome sequencing.
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DOI：
10.1093/bioinformatics/bts408
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发表时间：
2012-09-15
期刊：
影响因子：
--
通讯作者：
LaFramboise T
中科院分区：
文献类型：
--
作者：
Ruffalo M;Koyutürk M;Ray S;LaFramboise T
动机：几种软件工具专门用于将短的下一代测序读数与参考序列进行比对。这些工具中的一些会报告每个比对的映射质量分数原则上，这个质量分数告诉研究人员比对正确的可能性。然而，报告的映射质量往往与实际的准确性弱相关，许多映射的质量被低估，鼓励研究人员放弃正确的映射。此外，这些低质量的映射往往与基因组中的变异（单核苷酸和结构两者）相关，并且这样的映射在准确地鉴定基因组变异中是重要的。方法：我们开发了一种机器学习工具LoQuM（用于校准短读段映射的质量的LOgistic回归工具），以将可靠的映射质量评分分配给由任何比对工具返回的Illumina读段的映射。LoQuM使用读数（测序仪报告的碱基质量评分）和比对（匹配、错配和缺失的数量，比对工具返回的映射质量评分（如果可用）和映射数量）的统计数据作为分类特征，并使用模拟读数学习逻辑回归模型，该模型将这些特征与实际映射质量联系起来。结果如下：我们在ART短读模拟软件生成的独立数据集上测试了LoQuM的预测，并观察到LoQuM可以“复活”许多被比对工具分配为零质量分数的映射，因此可能被研究人员丢弃。我们还观察到，映射质量分数的重新校准大大提高了所谓的单核苷酸多态性的精度。可用性：LoQuM可在http://compbio.case.edu/loqum/上以开源形式提供。联系人：matthew. ruffalo@case.edu。
Motivation: Several software tools specialize in the alignment of short next-generation sequencing reads to a reference sequence. Some of these tools report a mapping quality score for each alignment—in principle, this quality score tells researchers the likelihood that the alignment is correct. However, the reported mapping quality often correlates weakly with actual accuracy and the qualities of many mappings are underestimated, encouraging the researchers to discard correct mappings. Further, these low-quality mappings tend to correlate with variations in the genome (both single nucleotide and structural), and such mappings are important in accurately identifying genomic variants. Approach: We develop a machine learning tool, LoQuM (LOgistic regression tool for calibrating the Quality of short read mappings, to assign reliable mapping quality scores to mappings of Illumina reads returned by any alignment tool. LoQuM uses statistics on the read (base quality scores reported by the sequencer) and the alignment (number of matches, mismatches and deletions, mapping quality score returned by the alignment tool, if available, and number of mappings) as features for classification and uses simulated reads to learn a logistic regression model that relates these features to actual mapping quality. Results: We test the predictions of LoQuM on an independent dataset generated by the ART short read simulation software and observe that LoQuM can ‘resurrect’ many mappings that are assigned zero quality scores by the alignment tools and are therefore likely to be discarded by researchers. We also observe that the recalibration of mapping quality scores greatly enhances the precision of called single nucleotide polymorphisms. Availability: LoQuM is available as open source at http://compbio.case.edu/loqum/. Contact: matthew.ruffalo@case.edu.
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30.8
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Alkan, Can;Kidd, Jeffrey M.;Marques-Bonet, Tomas;Aksay, Gozde;Antonacci, Francesca;Hormozdiari, Fereydoun;Kitzman, Jacob O.;Baker, Carl;Malig, Maika;Mutlu, Onur;Sahinalp, S. Cenk;Gibbs, Richard A.;Eichler, Evan E.
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Robinson A
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Huang, Weichun;Li, Leping;Marth, Gabor T.
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影响因子：
4.8
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Schmidt, Dominic;Wilson, Michael D.;Spyrou, Christiana;Brown, Gordon D.;Hadfield, James;Odom, Duncan T.
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Odom, Duncan T.