Abstract: Described herein are methods and systems for improving nucleic acid sequencing read quality. An exemplary method comprises receiving, at one or more processors, sequencing data comprising a plurality of sequencing reads; filtering the sequencing data, using the one or more processors, to remove sequencing reads for which an absence of an incorporated nucleotide was detected at three or more consecutive sequencing flow steps, thereby generating filtered sequencing data; determining, using the one or more processors, for each sequencing flow step of each sequencing read, a read quality metric based on one or more homopolymer probability values other than a highest homopolymer probability value; and trimming the terminus of one or more sequencing reads in the sequencing data based on the read quality metrics for a respective sequencing read, thereby generating trimmed sequencing data.