Various types of mutation and editing (M/E) events in miRNAs can change the stabilities of pre-miRNAs and/or complementarities between miRNAs and their targets.Small RNA (sRNA) high-throughput sequencing (HTS) profiles can contain many mutated and edited miRNAs.Systematic detection of miRNA mutation and editing sites from the huge volume of sRNA HTS profiles is computationally difficult,as high sensitivity and low false positive rate (FPR) are both required,We propose a novel method (named MiRME) for an accurate and fast detection of miRNA M/E sites using a progressive sequence alignment approach which refines sensitivity and improves FPR step-by-step.