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Journal Articles Nucleic Acids Research Year : 2023

OKseqHMM: a genome-wide replication fork directionality analysis toolkit


During each cell division, tens of thousands of DNA replication origins are co-ordinately activated to ensure the complete duplication of the human genome. However, replication fork progression can be challenged by many factors, including co-directional and head-on transcription-replication conflicts (TRC). Head-on TRCs are more dangerous for genome integrity. To study the direction of replication fork movement and TRCs, we developed a bioinformatics toolkit called OKseqHMM (https://github.com/CL-CHEN-Lab/OK-Seq, https://doi.org/10.5281/zenodo.7428883). Then, we used OKseqHMM to analyse a large number of datasets obtained by Okazaki fragment sequencing to directly measure the genome-wide replication fork directionality (RFD) and to accurately predict replication initiation and termination at a fine resolution in organisms including yeast, mouse and human. We also successfully applied our analysis to other genome-wide sequencing techniques that also contain RFD information (e.g. eSPAN, TrAEL-seq). Our toolkit can be used to predict replication initiation and fork progression direction genome-wide in a wide range of cell models and growth conditions. Comparing the replication and transcription directions allows identifying loci at risk of TRCs, particularly head-on TRCs, and investigating their role in genome instability by checking DNA damage data, which is of prime importance for human health.
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hal-03974116 , version 1 (05-02-2023)





Yaqun Liu, Xia Wu, Yves D’aubenton-Carafa, Claude Thermes, Chun-Long Chen. OKseqHMM: a genome-wide replication fork directionality analysis toolkit. Nucleic Acids Research, 2023, pp.gkac1239. ⟨10.1093/nar/gkac1239⟩. ⟨hal-03974116⟩
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