Fig. 3. Recording and decoding short digital text messages with DNA Typewriter.

a, Base64 binary-to-text was modified to assign 64 NNNGGA barcodes for TAPE-1 to 64 text characters. b, Illustration of the encoding strategy for “WHAT HATH GOD WROUGHT?”, which has 22 characters including whitespaces. The message is grouped into sets of four characters, converted to NNN barcodes according to the TAPE64 encoding table, and plasmids corresponding to each set are mixed at a ratio of 7:5:3:1 for transfection. To encode 22 characters, we sequentially transfected 5 sets of 4 characters and 1 set of 2 characters 3 days apart into PE2(+) 5×TAPE-1(+) HEK293T cells. c–e, Decoding of three messages based on sequencing of the following 5×TAPE-1 arrays: “WHAT HATH GOD WROUGHT?” (c), “MR. WATSON, COME HERE!” (d) and “BOUND FOREVER, DNA” (e). For each message, the full set of NNNGGA insertions was first identified and cotransfected sets of characters were then identified from the bigram transition matrix (left). Within each set of characters inferred to have been cotransfected, ordering was based on corrected unigram counts (middle), resulting in the final decoded message (right). Misordered characters within each recovered message are coloured purple, missing characters are coloured red with strikethrough, and unintended characters are coloured light blue. Both two-dimensional histogram and corrected read counts were calculated by combining sequencing reads over n = 3 independent transfection experiments. Read counts were corrected using the edit score for each insertion barcode.