背景回顾：Millions of species are currently being sequenced, and their genomes are being compared. Many of them have more complex genomes than model systems and raise novel challenges for genome alignment. 

提出问题：Widely used local alignment strategies often produce limited or incongruous results when applied to genomes with dispersed repeats, long indels, and highly diverse sequences. Moreover, alignment using many-to-many or reciprocal best hit approaches conflicts with well-studied patterns between species with different rounds of whole-genome duplication.  

软件开发：Here, we introduce Anchored Wavefront alignment (AnchorWave), which performs whole-genome duplication–informed collinear anchor identification between genomes and performs base pair–resolved global alignment for collinear blocks using a two-piece affine gap cost strategy.

软件测试：This strategy enables AnchorWave to precisely identify multikilobase indels generated by transposable element (TE) presence/absence variants (PAVs). When aligning two maize genomes, AnchorWave successfully recalled 87% of previously reported TE PAVs. By contrast, other genome alignment tools showed low power for TE PAV recall. AnchorWave precisely aligns up to three times more of the genome as position matches or indels than the closest competitive approach when comparing diverse genomes. Moreover, AnchorWave recalls transcription factor–binding sites at a rate of 1.05- to 74.85-fold higher than other tools with significantly lower false-positive alignments. 

结论：AnchorWave complements available genome alignment tools by showing obvious improvement when applied to genomes with dispersed repeats, active TEs, high sequence diversity, and whole-genome duplication variation.

 摘 要 

目前，我们对数百万个物种的基因组进行了测序，亟需对这些基因组之间进行比较研究。大多数物种的基因组比模式物种复杂得多，这对基因组间的比对形成了新的挑战。当对含有散在重复序列、大片段插入或缺失以及序列多样性很高的基因组时，大多基于局域比对的计算方法经常会有所限制，或者导致错误的比对结果。此外，采用many to many或者RBH的比对方法进行基因组比对时，会产生与物种全基因组复制或多倍化相矛盾的结果。本文中，作者开发了一套叫做AnchorWave的基因组比对工具，其对全基因组复制和基因组间的共线性区域进行锚点识别，使用WFA和2-piece affine gap cost策略进行碱基水平上的共线性区域比对。这种策略可以精确鉴定由于转座子存在/缺失变异产生的数个Kb级别的缺失。当进行两个玉米基因组比对时，AnchorWave能够成功比对出之前报道中约87%的TE PAVs。而其它类似的基因组比对工具对于TE PAV的比对率较低。再比对分化程度较高的基因组时，再鉴定位置匹配或者缺失方面，AnchorWave是其它比对方法的3倍以上。此外，AnchorWave比对转录因子结合位点是其它工具的1.05-74.85倍，并且假阳性的比对明显较低。AnchorWave软件的开发是对目前已有基因组比对软件的补充，在比对含有散在重复序列、转座子、序列多样性高以及WGD等变异的基因组时，AnchorWave的效果有较为明显的改进。 

 Edward S. Buckler