SVAtools for junction detection of genome-wide chromosomal rearrangements by mate-pair sequencing (MPseq)
SVAtools for junction detection of genome-wide chromosomal rearrangements by mate-pair sequencing (MPseq)
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DOI：
10.1016/j.cancergen.2017.11.009
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发表时间：
2018-02-01
期刊：
影响因子：
1.9
通讯作者：
Vasmatzis, George
中科院分区：
文献类型：
--
作者：
Johnson, Sarah H.;Smadbeck, James B.;Vasmatzis, George
使用长插入、配对末端基因组文库的配对测序（MPseq）是用于检测基因组结构变体的强大的下一代基于测序的方法。SVAtools是一组检测全基因组MPseq数据中染色体重排和大（>10 kb）拷贝数变异（CNV）的算法。SVAtools还可以预测基因破坏和基因融合，并表征复杂重排的基因组结构。为了说明SVAtools的连接检测方法提供全面分子核型的能力，将MPseq数据与先前通过传统细胞遗传学方法表征的一组样品进行了比较。在临床实验室环境中对29名患者进行的核型、FISH和染色体微阵列（CMA）共揭示了87种重排中的285个断点。SVAtools的连接检测方法检测到87%的这些断点，而核型，FISH和CMA分别为48%，42%和57%。断裂点分辨率也被报道为1 kb或更少，并揭示了标准细胞遗传学技术无法察觉的额外基因组重排复杂性。例如，通过CMA检测到的63%的CNV通过SVAtools的连接检测显示继发于重排而不是简单缺失或串联重复。与核型、FISH和CMA组合相比，SVAtools与MPseq提供了全面准确的全基因组连接检测，并提高了断点分辨率。这种分子核型分析的方法提供了相当大的诊断潜力，同时检测新的和经常性的基因组重排的遗传性和肿瘤性疾病。
Mate-pair sequencing (MPseq), using long-insert, paired-end genomic libraries, is a powerful next-generation sequencing-based approach for the detection of genomic structural variants. SVAtools is a set of algorithms to detect both chromosomal rearrangements and large (>10 kb) copy number variants (CNVs) in genome-wide MPseq data. SVAtools can also predict gene disruptions and gene fusions, and characterize the genomic structure of complex rearrangements.To illustrate the power of SVAtools' junction detection methods to provide comprehensive molecular karyotypes, MPseq data were compared against a set of samples previously characterized by traditional cytogenetic methods. Karyotype, FISH and chromosomal microarray (CMA), performed for 29 patients in a clinical laboratory setting, collectively revealed 285 breakpoints in 87 rearrangements. The junction detection methods of SVAtools detected 87% of these breakpoints compared to 48%, 42% and 57% for karyotype, FISH and CMA respectively. Breakpoint resolution was also reported to 1 kb or less and additional genomic rearrangement complexities not appreciable by standard cytogenetic techniques were revealed. For example, 63% of CNVs detected by CMA were shown by SVAtools' junction detection to occur secondary to a rearrangement other than a simple deletion or tandem duplication. SVAtools with MPseq provides comprehensive and accurate whole-genome junction detection with improved breakpoint resolution, compared to karyotype, FISH, and CMA combined. This approach to molecular karyotyping offers considerable diagnostic potential for the simultaneous detection of both novel and recurrent genomic rearrangements in hereditary and neoplastic disorders.