Department of Molecular Biology and Genetics, Cornell University, Ithaca, NY 14853, USA.
Bioinformatics. 2021 Nov 18;37(22):4001-4005. doi: 10.1093/bioinformatics/btab166.
Genomic DNA replicates according to a reproducible spatiotemporal program, with some loci replicating early in S phase while others replicate late. Despite being a central cellular process, DNA replication timing studies have been limited in scale due to technical challenges.
We present TIGER (Timing Inferred from Genome Replication), a computational approach for extracting DNA replication timing information from whole genome sequence data obtained from proliferating cell samples. The presence of replicating cells in a biological specimen leads to non-uniform representation of genomic DNA that depends on the timing of replication of different genomic loci. Replication dynamics can hence be observed in genome sequence data by analyzing DNA copy number along chromosomes while accounting for other sources of sequence coverage variation. TIGER is applicable to any species with a contiguous genome assembly and rivals the quality of experimental measurements of DNA replication timing. It provides a straightforward approach for measuring replication timing and can readily be applied at scale.
TIGER is available at https://github.com/TheKorenLab/TIGER.
Supplementary data are available at Bioinformatics online.
基因组 DNA 根据可重复的时空程序进行复制,一些基因座在 S 期早期复制,而其他基因座在晚期复制。尽管 DNA 复制是一个核心的细胞过程,但由于技术挑战,DNA 复制时间研究的规模一直受到限制。
我们提出了 TIGER(从基因组复制推断的时间),这是一种从增殖细胞样本获得的全基因组序列数据中提取 DNA 复制时间信息的计算方法。生物样本中存在复制细胞会导致基因组 DNA 的非均匀表示,这取决于不同基因组基因座的复制时间。通过分析染色体上的 DNA 拷贝数,并考虑其他序列覆盖变化的来源,可以在基因组序列数据中观察到复制动力学。TIGER 适用于具有连续基因组组装的任何物种,与 DNA 复制时间的实验测量质量相当。它提供了一种测量复制时间的简单方法,可以大规模应用。
TIGER 可在 https://github.com/TheKorenLab/TIGER 上获得。
补充数据可在《生物信息学》在线获得。