Nucleotide-resolution analysis of structural variants using BreakSeq and a breakpoint library.
Nucleotide-resolution analysis of structural variants using BreakSeq and a breakpoint library.
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DOI：
10.1038/nbt.1600
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发表时间：
2010-01
影响因子：
46.9
通讯作者：
Gerstein MB
中科院分区：
文献类型：
--
作者：
Lam HY;Mu XJ;Stütz AM;Tanzer A;Cayting PD;Snyder M;Kim PM;Korbel JO;Gerstein MB
结构变异（SVs）是人类基因组变异的主要来源；然而，在核苷酸分辨率上表征它们仍然具有挑战性。在这里，我们从整理和标准化约2000个已发表的sv中组装了一个核苷酸分辨率的断点库。对于每个断点，我们推断其祖先状态（通过与灵长类基因组的比较）及其形成机制（例如，非等位基因同源重组，NAHR）。我们从基因组标记、染色体位置、序列基序和物理性质等方面对断点序列进行了表征，发现插入和缺失的发生比以前报道的更为平衡，并且nahr形成的断点与相对刚性、稳定的DNA螺旋相关。最后，我们展示了一种方法，BreakSeq，用于扫描来自短读测序基因组的reads与我们的断点库，以准确识别以前被忽视的sv，然后我们通过PCR验证。随着新数据的出现，我们期望我们的BreakSeq方法将变得更加敏感，并促进个人基因组的快速SV基因分型。
Structural variants (SVs) are a major source of human genomic variation; however, characterizing them at nucleotide resolution remains challenging. Here we assemble a library of breakpoints at nucleotide resolution from collating and standardizing ~2,000 published SVs. For each breakpoint, we infer its ancestral state (through comparison to primate genomes) and its mechanism of formation (e.g., non-allelic homologous recombination, NAHR). We characterize breakpoint sequences with respect to genomic landmarks, chromosomal location, sequence motifs and physical properties, finding that the occurrence of insertions and deletions is more balanced than previously reported and that NAHR-formed breakpoints are associated with relatively rigid, stable DNA helices. Finally, we demonstrate an approach, BreakSeq, for scanning the reads from short-read sequenced genomes against our breakpoint library to accurately identify previously overlooked SVs, which we then validate by PCR. As new data become available, we expect our BreakSeq approach will become more sensitive and facilitate rapid SV genotyping of personal genomes.
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影响因子：
30.8
作者：
Iafrate, AJ;Feuk, L;Lee, C
通讯作者：
Lee, C
影响因子：
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作者：
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模因套件：用于发现和搜索的工具。
影响因子：
14.9
作者：
Bailey TL;Boden M;Buske FA;Frith M;Grant CE;Clementi L;Ren J;Li WW;Noble WS
通讯作者：
Noble WS
影响因子：
30.8
作者：
Campbell, Peter J.;Stephens, Philip J.;Pleasance, Erin D.;O'Meara, Sarah;Li, Heng;Santarius, Thomas;Stebbings, Lucy A.;Leroy, Catherine;Edkins, Sarah;Hardy, Claire;Teague, Jon W.;Menzies, Andrew;Goodhead, Ian;Turner, Daniel J.;Clee, Christopher M.;Quail, Michael A.;Cox, Antony;Brown, Clive;Durbin, Richard;Hurles, Matthew E.;Edwards, Paul A. W.;Bignell, Graham R.;Stratton, Michael R.;Futreal, P. Andrew
通讯作者：
Futreal, P. Andrew
DOI：
10.1093/bioinformatics/btn176
发表时间：
2008-07-01
期刊：
Bioinformatics (Oxford, England)
影响因子：
--
作者：
Lee S;Cheran E;Brudno M
通讯作者：
Brudno M