We employ two methodologies for measuring bias. Per-base bias measurements, which rely on deep-coverage sequencing, are hypothesis-free and ideal for discovering new types of bias. Motif bias measurements, which require only shallow-coverage sequencing, are ideal for comparisons across experimental conditions and for monitoring ongoing sequencing pipeline performance at known bias-prone sequence contexts and locations. Bias motif monitoring plays a useful role by providing a critical metric in determining and ameliorating the sources of sequencing bias. Together these methodologies can be used to compare platforms, to measure the utility of combining data from multiple platforms, and to determine the extent to which coverage bias is described by the statistics of known motifs.
