Ramy Khabbaz, Jérémy Mateos, Marc Antonini et al.
The biochemical processes underlying DNA data storage, including synthesis, amplification, and sequencing, are inherently noisy. Consequently, base-level insertion, deletion, and substitution (IDS) errors, as well as sequence-level dropouts, occur and pose major challenges for reliable data retrieval. Here we introduce DNA-MGC+, a DNA storage codec designed to enable reliable and resource-efficient data retrieval under diverse operating conditions. We evaluate DNA-MGC+ across a wide range of in silico and in vitro settings, including experiments with both Illumina and Nanopore sequencing, and show that it consistently outperforms existing codecs. In particular, DNA-MGC+ achieves simultaneous gains in sequencing depth requirements, read cost, decoding time, storage density, and error-correction capability under explicit reliability constraints. Notable results include reliable decoding under IDS error rates of up to 24% in synthetic scenarios, and reliable retrieval at sequencing depths below 3x with read costs below 3.5 bits/nt under electrochemical synthesis for both Illumina and Nanopore sequencing.