STARRPeaker: uniform processing and accurate identification of STARR-seq active regions.

STARRPeaker: uniform processing and accurate identification of STARR-seq active regions.
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DOI:
10.1186/s13059-020-02194-x
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发表时间:
2020-12-08
期刊:
影响因子:
12.3
通讯作者:
Gerstein M
Gerstein M
中科院分区:
生物学1区
文献类型:
--
作者:
Lee D;Shi M;Moran J;Wall M;Zhang J;Liu J;Fitzgerald D;Kyono Y;Ma L;White KP;Gerstein M

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STARR-seq技术采用了越来越复杂的基因组文库,并增加了测序深度。复杂性和深度增加的一个问题是STARR-seq实验中的覆盖率是不均匀的、过度分散的,并且经常被测序偏差(例如GC含量)混淆。此外,STARR-seq读数受到RNA二级结构和热力学稳定性的混淆。为了解决这些潜在的混杂因素,我们开发了一个负二项回归框架,用于统一处理STARR-seq数据,称为STARRPeaker。此外,为了帮助我们的工作,我们从HepG 2和K562人类细胞系中生成了全基因组STARR-seq数据,并应用STARRPeaker全面而无偏见地调用其中的增强子。在线版本包含补充材料,可通过10.1186/s13059-020-02194-x获得。
STARR-seq technology has employed progressively more complex genomic libraries and increased sequencing depths. An issue with the increased complexity and depth is that the coverage in STARR-seq experiments is non-uniform, overdispersed, and often confounded by sequencing biases, such as GC content. Furthermore, STARR-seq readout is confounded by RNA secondary structure and thermodynamic stability. To address these potential confounders, we developed a negative binomial regression framework for uniformly processing STARR-seq data, called STARRPeaker. Moreover, to aid our effort, we generated whole-genome STARR-seq data from the HepG2 and K562 human cell lines and applied STARRPeaker to comprehensively and unbiasedly call enhancers in them. The online version contains supplementary material available at 10.1186/s13059-020-02194-x.
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