Denoising PCR-amplified metagenome data.

Denoising PCR-amplified metagenome data.
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DOI:
10.1186/1471-2105-13-283
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发表时间:
2012-10-31
期刊:
影响因子:
3
通讯作者:
Holmes SP
Holmes SP
中科院分区:
生物学4区
文献类型:
--
作者:
Rosen MJ;Callahan BJ;Fisher DS;Holmes SP

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PCR扩增和高通量测序理论上能够表征天然微生物和病毒群体中最小规模的多样性,但这些方法中的每一种都引入了难以与真正的生物多样性区分开的随机误差。已经提出了几种方法去噪这些数据,但缺乏速度或准确性。我们介绍了一种新的去噪算法,我们称之为DADA(分裂扩增子去噪算法)。在没有训练数据的情况下,DADA推断产生宏基因组数据集的样本基因型和误差参数。我们展示了在罗氏454平台上测序的对照数据的性能,并将结果与目前最准确的去噪软件AmpliconNoise进行了比较。DADA比AmpliconNoise更准确,速度也快了一个数量级。它消除了对训练数据建立错误参数的需要,充分利用了序列丰度信息,并能够包含上下文相关的PCR错误率。它应该容易扩展到其他测序平台,如Illumina。
PCR amplification and high-throughput sequencing theoretically enable the characterization of the finest-scale diversity in natural microbial and viral populations, but each of these methods introduces random errors that are difficult to distinguish from genuine biological diversity. Several approaches have been proposed to denoise these data but lack either speed or accuracy. We introduce a new denoising algorithm that we call DADA (Divisive Amplicon Denoising Algorithm). Without training data, DADA infers both the sample genotypes and error parameters that produced a metagenome data set. We demonstrate performance on control data sequenced on Roche’s 454 platform, and compare the results to the most accurate denoising software currently available, AmpliconNoise. DADA is more accurate and over an order of magnitude faster than AmpliconNoise. It eliminates the need for training data to establish error parameters, fully utilizes sequence-abundance information, and enables inclusion of context-dependent PCR error rates. It should be readily extensible to other sequencing platforms such as Illumina.
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