HiLive：测序时对Illumina reads进行实时映射

HiLive: real-time mapping of illumina reads while sequencing.

作者信息

Lindner Martin S, Strauch Benjamin, Schulze Jakob M, Tausch Simon H, Dabrowski Piotr W, Nitsche Andreas, Renard Bernhard Y

机构信息

Research Group Bioinformatics (NG 4), Robert Koch Institute, Berlin, Germany.

Centre for Biological Threats and Special Pathogens, Robert Koch Institute, Berlin, Germany.

出版信息

Bioinformatics. 2017 Mar 15;33(6):917-319. doi: 10.1093/bioinformatics/btw659.

DOI:10.1093/bioinformatics/btw659

PMID:27794555

Abstract

MOTIVATION

Next Generation Sequencing is increasingly used in time critical, clinical applications. While read mapping algorithms have always been optimized for speed, they follow a sequential paradigm and only start after finishing of the sequencing run and conversion of files. Since Illumina machines write intermediate output results, HiLive performs read mapping while still sequencing and thereby drastically reduces crucial overall sample analysis time, e.g. in precision medicine.

METHODS

We present HiLive as a novel real time read mapper that implements a k-mer based alignment strategy. HiLive continuously reads intermediate BCL files produced by Illumina sequencers and then extends initial k-mer matches by increasingly produced data from the sequencer.

RESULTS

We applied HiLive on real human transcriptome data to show that final read alignments are reported within few minutes after the end of a full Illumina HiSeq 1500 run, while already the necessary conversion to FASTQ files as the standard input to current read mapping methods takes roughly five times as long. Further, we show on simulated and real data that HiLive has comparable accuracy to recent read mappers.

AVAILABILITY AND IMPLEMENTATION

HiLive and its source code are freely available from https://gitlab.com/SimonHTausch/HiLive .

CONTACT

renardB@rki.de.

SUPPLEMENTARY INFORMATION

Supplementary data are available at Bioinformatics online.

摘要

动机

新一代测序技术越来越多地应用于时间紧迫的临床应用中。虽然读段比对算法一直以来都在速度方面进行了优化，但它们遵循的是顺序范式，只有在测序运行结束和文件转换完成后才开始。由于Illumina机器会写入中间输出结果，HiLive在读段仍在测序时就进行读段比对，从而大幅缩短了关键的总体样本分析时间，例如在精准医学中。

方法

我们提出HiLive作为一种新颖的实时读段比对器，它实现了基于k-mer的比对策略。HiLive持续读取Illumina测序仪生成的中间BCL文件，然后根据测序仪不断生成的数据扩展初始的k-mer匹配。

结果

我们将HiLive应用于真实的人类转录组数据，结果表明，在Illumina HiSeq 1500完整运行结束后的几分钟内就能报告最终的读段比对结果，而将其转换为FASTQ文件（作为当前读段比对方法的标准输入）所需的时间大约是前者的五倍。此外，我们在模拟数据和真实数据上均表明，HiLive与近期的读段比对器具有相当的准确性。