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kmer2vec:一种基于 word2vec 嵌入的 DNA 序列比较新方法。

kmer2vec: A Novel Method for Comparing DNA Sequences by word2vec Embedding.

机构信息

Department of Mathematical Sciences, Tsinghua University, Beijing, China.

Department of Mathematics, Statistics, and Computer Science, The University of Illinois at Chicago, Chicago, Illinois, USA.

出版信息

J Comput Biol. 2022 Sep;29(9):1001-1021. doi: 10.1089/cmb.2021.0536. Epub 2022 May 20.

Abstract

The comparison of DNA sequences is of great significance in genomics analysis. Although the traditional multiple sequence alignment (MSA) method is popularly used for evolutionary analysis, optimally aligning sequences becomes computationally intractable when increases due to the intrinsic computational complexity of MSA. Despite numerous -mer alignment-free methods being proposed, the existing -mer alignment-free methods may not truly capture the contextual structures of the sequences. In this study, we present a novel -mer contextual alignment-free method (called kmer2vec), in which the sequence -mers are semantically embedded to word2vec vectors, an essential technique in natural language processing. Consequently, the method converts each DNA/RNA sequence into a point in the word2vec high-dimensional space and compares DNA sequences in the space. Because the word2vec vectors are trained from the contextual relationship of -mers in the genomes, the method may extract valuable structural information from the sequences and reflect the relationship among them properly. The proposed method is optimized on the parameters from word2vec training and verified in the phylogenetic analysis of large whole genomes, including coronavirus and bacterial genomes. The results demonstrate the effectiveness of the method on phylogenetic tree construction and species clustering. The method running speed is much faster than that of the MSA method, especially the phylogenetic relationships constructed by the kmer2vec method are more accurate than the conventional -mer alignment-free method. Therefore, this approach can provide new perspectives for phylogeny and evolution and make it possible to analyze large genomes. In addition, we discuss special parameterization in the -mer word2vec embedding construction. An effective tool for rapid SARS-CoV-2 typing can also be derived when combining kmer2vec with clustering methods.

摘要

序列比对在基因组学分析中具有重要意义。虽然传统的多重序列比对(MSA)方法常用于进化分析,但由于 MSA 的固有计算复杂性,当 增加时,最佳对齐序列在计算上变得难以处理。尽管已经提出了许多无 -mer 比对方法,但现有的无 -mer 比对方法可能无法真正捕捉到序列的上下文结构。在本研究中,我们提出了一种新的无 -mer 上下文无比对方法(称为 kmer2vec),其中序列的 -mers 被语义嵌入到 word2vec 向量中,这是自然语言处理中的一项重要技术。因此,该方法将每个 DNA/RNA 序列转换为 word2vec 高维空间中的一个点,并在空间中比较 DNA 序列。由于 word2vec 向量是从基因组中 -mers 的上下文关系中训练得到的,因此该方法可以从序列中提取有价值的结构信息,并正确反映它们之间的关系。该方法在 word2vec 训练的参数上进行了优化,并在包括冠状病毒和细菌基因组在内的大型全基因组的系统发育分析中进行了验证。结果表明该方法在构建系统发育树和物种聚类方面的有效性。该方法的运行速度比 MSA 方法快得多,特别是 kmer2vec 方法构建的系统发育关系比传统的无 -mer 比对方法更准确。因此,这种方法可以为系统发育和进化提供新的视角,并使其有可能分析大型基因组。此外,我们还讨论了 -mer word2vec 嵌入构建中的特殊参数化。当将 kmer2vec 与聚类方法结合使用时,还可以衍生出一种快速 SARS-CoV-2 分型的有效工具。

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