Genome-wide detection of short tandem repeat expansions by long-read sequencing.
Genome-wide detection of short tandem repeat expansions by long-read sequencing.
复制标题
DOI：
10.1186/s12859-020-03876-w
复制
发表时间：
2020-12-28
影响因子：
3
通讯作者：
Wang K
中科院分区：
文献类型：
--
作者：
Liu Q;Tong Y;Wang K
短串联重复序列（STR）或“微卫星”是一段DNA，其中特定的基序（通常< 10个碱基对）重复多次。STR在整个人类基因组中是丰富的，并且特定的重复扩增可能与人类疾病相关。长读段测序与生物信息学工具相结合，能够估计STR的重复计数。然而，除了少数已知的与疾病相关的可疑交易报告外，大多数可疑交易报告在人群中的正常重复计数范围并不为人所知，这妨碍了对可能与人类疾病相关的可疑交易报告进行优先排序。在这项研究中，我们扩展了计算工具RepeatHMM，使用人类基因组上的21个长读序测序数据集来推断432，604个STR的正常范围，并建立了一个名为RepeatHMM-DB的基因组规模数据库，其中包含这些STR的正常重复范围。对13个已知重复序列的评价表明，推断的重复序列范围对来自人群规模研究的文献中报道的重复序列范围提供了良好的估计。该数据库与RepeatHMM等重复扩增估计工具一起，能够对新测序的基因组中的重复区域进行基因组规模的扫描，以识别疾病相关的重复扩增。作为使用RepeatHMM-DB的案例研究，我们评估了20例脊髓小脑共济失调3型（SCA 3）患者和5名未受影响的个体的ATXN 3的CAG重复序列，并正确分类每个个体。总之，RepeatHMM-DB可以促进从患有未诊断疾病的患者的全基因组长读段测序数据中优先考虑和识别疾病相关STR。RepeatHMM-DB被合并到RepeatHMM中，可在https://github.com/WGLab/RepeatHMM上获得。
Short tandem repeat (STR), or “microsatellite”, is a tract of DNA in which a specific motif (typically < 10 base pairs) is repeated multiple times. STRs are abundant throughout the human genome, and specific repeat expansions may be associated with human diseases. Long-read sequencing coupled with bioinformatics tools enables the estimation of repeat counts for STRs. However, with the exception of a few well-known disease-relevant STRs, normal ranges of repeat counts for most STRs in human populations are not well known, preventing the prioritization of STRs that may be associated with human diseases. In this study, we extend a computational tool RepeatHMM to infer normal ranges of 432,604 STRs using 21 long-read sequencing datasets on human genomes, and build a genomic-scale database called RepeatHMM-DB with normal repeat ranges for these STRs. Evaluation on 13 well-known repeats show that the inferred repeat ranges provide good estimation to repeat ranges reported in literature from population-scale studies. This database, together with a repeat expansion estimation tool such as RepeatHMM, enables genomic-scale scanning of repeat regions in newly sequenced genomes to identify disease-relevant repeat expansions. As a case study of using RepeatHMM-DB, we evaluate the CAG repeats of ATXN3 for 20 patients with spinocerebellar ataxia type 3 (SCA3) and 5 unaffected individuals, and correctly classify each individual. In summary, RepeatHMM-DB can facilitate prioritization and identification of disease-relevant STRs from whole-genome long-read sequencing data on patients with undiagnosed diseases. RepeatHMM-DB is incorporated into RepeatHMM and is available at https://github.com/WGLab/RepeatHMM.
登录
查看更多内容
影响因子：
14.9
作者：
Highnam G;Franck C;Martin A;Stephens C;Puthige A;Mittelman D
通讯作者：
Mittelman D
重复扩张疾病。
影响因子：
--
作者：
Paulson H
通讯作者：
Paulson H
影响因子：
56.9
作者：
KREMER, EJ;PRITCHARD, M;RICHARDS, RI
通讯作者：
RICHARDS, RI
DOI：
10.1073/pnas.94.14.7452
发表时间：
1997-07-08
影响因子：
11.1
作者：
Cossee, M;Schmitt, M;Koenig, M
通讯作者：
Koenig, M
影响因子：
7
作者：
Schneider, Valerie A.;Graves-Lindsay, Tina;Church, Deanna M.
通讯作者：
Church, Deanna M.