  A method for designing sequencing barcodes that can withstand a large number
of insertion, deletion and substitution errors and are suitable for use in
multiplex single-molecule real-time sequencing is presented. The manuscript
focuses on the design of barcodes for full-length single-pass reads, impaired
by challenging error rates in the order of 11%. To the authors' knowledge, this
is the first method to specifically address this problem without requiring
upstream quality improvement. The proposed barcodes can multiplex hundreds or
thousands of samples while achieving sample misassignment probabilities as low
as $10^{-7}$, and are designed to be compatible with chemical constraints
imposed by the sequencing process. Software for constructing watermark barcode
sets and demultiplexing barcoded reads, together with example sets of barcodes
and synthetic barcoded reads, are freely available at
www.cifasis-conicet.gov.ar/ezpeleta/NS-watermark.
