Exploring Systematic Errors in Sequencing Technologies

DNA sequencing technologies of second and third generations have revolutionized genome sequencing. However, all sequencing technologies make sequencing errors i.e. make mistakes while calling bases. The issues caused by random errors can be mitigated by redundancy in sequencing. But accumulation of errors at particular genomic sites have been observed in reads from second generation sequencing instruments in the past. This kind of errors, termed systematic errors, are difficult to deal with and may lead to incorrect genome assemblies and variant calls. Here a statistical approach to detect systematic errors and to determine associated motifs is presented. The approach is general purpose and can be applied to any sequencing technology. First sequenced reads from a second generation technology, Illumina are explored and systematic errors reported previously are confirmed. Data from third generation technologies, Pacific Biosciences and Oxford Nanopore are then analyzed and potential systematic errors and motifs associated with them are identified.