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Sequence-specific prediction of the efficiencies of adenine and cytosine base editors


Base editors, including adenine base editors (ABEs)1 and cytosine base editors (CBEs)2,3, are widely used to induce point mutations. However, determining whether a specific nucleotide in its genomic context can be edited requires time-consuming experiments. Furthermore, when the editable window contains multiple target nucleotides, various genotypic products can be generated. To develop computational tools to predict base-editing efficiency and outcome product frequencies, we first evaluated the efficiencies of an ABE and a CBE and the outcome product frequencies at 13,504 and 14,157 target sequences, respectively, in human cells. We found that there were only modest asymmetric correlations between the activities of the base editors and Cas9 at the same targets. Using deep-learning-based computational modeling, we built tools to predict the efficiencies and outcome frequencies of ABE- and CBE-directed editing at any target sequence, with Pearson correlations ranging from 0.50 to 0.95. These tools and results will facilitate modeling and therapeutic correction of genetic diseases by base editing.

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Fig. 1: Characterization of adenine and CBEs based on large-scale activity data.
Fig. 2: Development and evaluation of computational models predicting both efficiencies and outcomes of ABE- and CBE-induced base conversion at given target sequences.
Fig. 3: Predicted results for ABE- and CBE-induced modeling and correction of disease-relevant human point mutations.

Data availability

The deep sequencing data from this study have been submitted to the National Center for Biotechnology Information (NCBI) Sequence Read Archive under accession number SRP150719 (PRJNA476544). The data sets used in this study are provided as Supplementary Tables 2, 3 and 4.

Code availability

Source code for DeepABE, DeepCBE, DeepCBE-CA and custom Python scripts used for the base-editing frequency and outcome calculations are available on github (at and


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We are grateful to W. Wurst and O. Ortiz for providing the split-Cas9 plasmids. We thank J. Lee, J. Kweon, Y. Kim and G. Yu for technical assistance. We are also grateful to S. Park and Y. Kim for assisting with the experiments. This work was supported in part by the National Research Foundation of Korea (grant nos. 2017R1A2B3004198 (H.K.), 2017M3A9B4062403 (H.K.) and 2018R1A5A2025079 (H.K.)), Brain Korea 21 Plus Project (Yonsei University College of Medicine), Yonsei University Future-leading Research Initiative of 2015 (Challenge; grant no. RMS2 2015-22-0092) and the Korean Health Technology R&D Project, Ministry of Health and Welfare, Republic of Korea (grant nos. HI17C0676 (H.K.) and HI16C1012 (H.K.)).

Author information

Authors and Affiliations



M.S. performed experiments to build data sets of efficiencies and outcomes of base editing at integrated and endogenous sites. Y.K. and S.-Y.S. critically assisted the base-editing data generation by M.S., S.L., S.M., S.Y., M.S. and H.K.K. developed the framework and carried out the model training, computational validation and development of the web tools. J.P. and J.W.C. contributed substantially to bioinformatics analyses. Z.Q., J.H.K. and H.C.K. contributed to experiments using human iPSCs. H.H.K. conceived and designed the study. H.K.K., M.S., S.L. and H.H.K. analyzed the data and wrote the manuscript.

Corresponding author

Correspondence to Hyongbum Henry Kim.

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Competing interests

Yonsei University has filed a patent application based on this work, in which M.S., H.K.K., S.L. and H.H.K. are coinventors (patent no. PCT/KR2019/011166).

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Supplementary information

Supplementary Information

Supplementary Text, Figs. 1–12 and Table 1.

Reporting Summary

Supplementary Table 2

Data sets of ABE- and CBE-directed target conversion efficiencies and edited sequence outcomes at integrated sequences.

Supplementary Table 3

Data sets of ABE- and CBE-directed target conversion efficiencies and edited sequence outcomes at endogenous sites.

Supplementary Table 4

Data subsets of Endo_ABE and Endo_CBE obtained by stratified random sampling and the exact P value for Fig. 2e.

Supplementary Table 5

The results of computational prediction of the base-editing efficiencies and outcomes for the ABE- and CBE-directed generation and correction of pathogenic/likely pathogenic point mutations.

Supplementary Table 6

Oligonucleotides used in this study.

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Song, M., Kim, H.K., Lee, S. et al. Sequence-specific prediction of the efficiencies of adenine and cytosine base editors. Nat Biotechnol 38, 1037–1043 (2020).

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