DNA is an attractive medium for digital data storage. When data is stored on DNA, errors occur, which makes error-correcting coding techniques critical for reliable DNA data storage. To reduce the errors, a common technique is to include constraints that avoid homopolymers (consecutive repeated nucleotides) and balance the GC content, as sequences with homopolymers and unbalanced GC content are often associated with higher error rates. However, constrained coding comes at the cost of an increase in redundancy. An alternative is to control errors by randomizing the sequences, embracing errors, and paying for them with additional coding redundancy. In this paper, we determine the error regimes in which embracing substitutions is more efficient than constrained coding for DNA data storage. Our results suggest that constrained coding for substitution errors is inefficient for existing DNA data storage systems. Theoretical analysis indicates that for constrained coding to be efficient, the increase in substitution errors for nucleotides in homopolymers and sequences with unbalanced GC content must be very large. Additionally, empirical results show that the increase in substitution, deletion, and insertion rates for these nucleotides is minimal in existing DNA storage systems.
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