A hybrid and scalable error correction algorithm for indel and substitution errors of long reads

A hybrid and scalable error correction algorithm for indel and substitution errors of long reads

Abstract

Background

Long-read sequencing has shown the promises to overcome the short length limitations of second-generation sequencing by providing more complete assembly. However, the computation of the long sequencing reads is challenged by their higher error rates (e.g., 13% vs. 1%) and higher cost ($0.3 vs. $0.03 per Mbp) compared to the short reads.

Methods

In this paper, we present a new hybrid error correction tool, called ParLECH (Parallel Long-read Error Correction using Hybrid methodology). The error correction algorithm of ParLECH is distributed in nature and efficiently utilizes the k-mer coverage information of high throughput Illumina short-read sequences to rectify the PacBio long-read sequences.ParLECH first constructs a de Bruijn graph from the short reads, and then replaces the indel error regions of the long reads with their corresponding widest path (or maximum min-coverage path) in the short read-based de Bruijn graph. ParLECH then utilizes the k-mer coverage information of the short reads to divide each long read into a sequence of low and high coverage regions, followed by a majority voting to rectify each substituted error base.

Results

ParLECH outperforms latest state-of-the-art hybrid error correction methods on real PacBio datasets. Our experimental evaluation results demonstrate that ParLECH can correct large-scale real-world datasets in an accurate and scalable manner. ParLECH can correct the indel errors of human genome PacBio long reads (312 GB) with Illumina short reads (452 GB) in less than 29 h using 128 compute nodes. ParLECH can align more than 92% bases of an E. coli PacBio dataset with the reference genome, proving its accuracy.

Conclusion

ParLECH can scale to over terabytes of sequencing data using hundreds of computing nodes. The proposed hybrid error correction methodology is novel and rectifies both indel and substitution errors present in the original long reads or newly introduced by the short reads.

一种混合和可扩展的错误修正算法的indel和替换错误的长读取
摘要

背景
长读测序  有望通过提供  更完整的组装 来克服 第二代测序的短长度限制。
然而，与短序列相比，长序列的误差率(13% vs. 1%)和成本(0.3 vs. 0.03 / Mbp)较高，这对长序列的计算带来了挑战。
方法
在本文中，我们提出了一个新的混合纠错工具，称为ParLECH(使用混合方法的并行长读纠错)。
ParLECH的纠错算法是分布式的，有效地利用高通量Illumina短读序列的k-mer覆盖信息对PacBio长读序列进行纠错。
ParLECH首先从短读取构建一个de Bruijn图，然后将长读取的indel错误区域替换为基于短读取的de Bruijn图中对应的最宽路径(或最大最小覆盖路径)。
然后，ParLECH利用短读的k-mer覆盖信息，将每个长读划分为一个低覆盖和高覆盖区域的序列，然后通过多数投票来修正每个替代错误碱基。

结果
在真实的PacBio数据集上，ParLECH胜过最新的最先进的混合错误修正方法。
我们的实验评估结果表明，ParLECH能够以一种准确和可扩展的方式修正大规模真实数据集。
ParLECH使用128个计算节点，可以在29小时内纠正人类基因组PacBio长读(312 GB)和Illumina短读(452 GB)的indel错误。
ParLECH可以将大肠杆菌PacBio数据集92%以上的碱基与参考基因组进行比对，证明其准确性。

结论
使用数百个计算节点，ParLECH可以扩展到超过tb的排序数据。
提出的混合误差校正方法是一种新颖的方法，它既纠正了原长读中存在的indel和替换误差，也纠正了短读中新引入的indel(插入删除)和替换误差。