RT Journal Article
SR Electronic
T1 Topologically Dependent Abundance of Spontaneous DNA Damage in Single Human Cells
JF bioRxiv
FD Cold Spring Harbor Laboratory
SP 859686
DO 10.1101/859686
A1 Qiangyuan Zhu
A1 Yichi Niu
A1 Michael Gundry
A1 Kuanwei Sheng
A1 Muchun Niu
A1 Chenghang Zong
YR 2019
UL http://biorxiv.org/content/early/2019/12/01/859686.abstract
AB In the studies of single-cell genomics, the large endeavor has been focusing on the detection of the permanent changes in the genome. On the other hand, spontaneous DNA damage frequently occurs and results in transient single-stranded changes to the genome until they are repaired. So far, successful profiling of these dynamic changes has not been demonstrated by single-cell whole-genome amplification methods. Here we reported a novel single-cell WGA method: Linearly Produced Semiamplicon based Split Amplification Reaction (LPSSAR), which allows, for the first time, the whole-genome detection of the DNA damage associated variants (dSNVs) in single human cells. The sequence-based detection of dSNVs allows the direct characterization of the major damage signature that occurred in human cells. In the analysis of the abundance of dSNVs along the genome, interestingly, we observed two modules of dSNV abundance, instead of a homogeneous abundance of dSNVs. We showed that the two modules are associated with the A/B topological compartments of the genome. This result suggests that the genome topology directly influences the genome stability. Furthermore, with the detection of the large number of dSNVs in single cells, we showed that only when the de novo mutations can be distinguished from the dSNVs, can a reliable estimation of de novo mutations be achieved.