Hound: a novel tool for automated mapping of genotype to phenotype in bacterial genomes assembled de novo
Hound: a novel tool for automated mapping of genotype to phenotype in bacterial genomes assembled de novo
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DOI：
10.1093/bib/bbae057
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发表时间：
2024-02-21
影响因子：
9.5
通讯作者：
Avison，Matthew B.
中科院分区：
文献类型：
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作者：
Reding，Carlos;Satapoomin，Naphat;Avison，Matthew B.
越来越多的证据表明，微生物物种具有很强的种内遗传异质性。这对于通常依赖参考基因组来指导组装过程的原核生物基因组的分析可能是有问题的。因此，参考基因组和样本基因组之间的差异将在最终组装中引入错误，危及从结构变异到点突变的检测——这对抗生素耐药性的基因组监测至关重要。在这里，我们展示了Hound，一个整合了公开可用工具的管道，用于组装原核生物基因组，通过相似性检测用户给定的基因，以报告在编码序列，启动子中发现的突变，以及组装中的相对基因拷贝数。重要的是，Hound可以使用查询序列作为合并组合的指导，并重建被组装器碎片化的基因。为了展示Hound，我们筛选了从养殖动物和人类感染中分离的5032个细菌全基因组序列，使用blatem1编码的氨基酸序列，检测和预测由该基因过表达驱动的对阿莫西林/克拉维酸的耐药性。我们相信这个工具可以促进对目前缺乏参考基因组的原核生物物种的分析，并且可以扩大规模以建立基因组监测的自动化系统，或者缩小规模以整合到抗生素敏感性护理点诊断中。
Increasing evidence suggests that microbial species have a strong within species genetic heterogeneity. This can be problematic for the analysis of prokaryote genomes, which commonly relies on a reference genome to guide the assembly process. Differences between reference and sample genomes will therefore introduce errors in final assembly, jeopardizing the detection from structural variations to point mutations—critical for genomic surveillance of antibiotic resistance. Here we present Hound, a pipeline that integrates publicly available tools to assemble prokaryote genomesde novo, detect user-given genes by similarity to report mutations found in the coding sequence, promoter, as well as relative gene copy number within the assembly. Importantly, Hound can use the query sequence as a guide to merge contigs, and reconstruct genes that were fragmented by the assembler. To showcase Hound, we screened through 5032 bacterial whole-genome sequences isolated from farmed animals and human infections, using the amino acid sequence encoded byblaTEM-1, to detect and predict resistance to amoxicillin/clavulanate which is driven by over-expression of this gene. We believe this tool can facilitate the analysis of prokaryote species that currently lack a reference genome, and can be scaled either up to build automated systems for genomic surveillance or down to integrate into antibiotic susceptibility point-of-care diagnostics.