A technique is disclosed for performing sequencing of polymers such as DNA and RNA. A sample containing multiple sites to be sequenced is cyclically subjected to attachment of nucleotides, and imaging. A digital mask corresponding to sites of interest in the sample array is generated and image data for the sites is processed differently from image data not corresponding to sites of interest. The latter may be discarded during the sequencing operation. The use of the mask improves computational efficiency and reduces memory allocated for the image data during sequencing.