The R package for GenIE analysis is designed to analyze the next-generation sequencing output from a set of GenIE experimental replicates. GenIE (genome-editing interrogation of enhancers) is an experimental method to evaluate the effects of individual single-nucleotide polymorphisms (SNPs) on gene transcription. It is based on targeted CRISPR-Cas9 genome editing in cultured cells to produce indels at a target locus, optionally with a homology-dependent recombination (HDR) construct to create precisely defined genomic changes. Following this, both genomic DNA (gDNA) and RNA are extracted from the same pool of cells, then complementary DNA (cDNA) is generated from the RNA. Both gDNA and cDNA are amplified with locus-specific PCR primers, in multiple replicates, and libraries of the experimental replicates are prepared for next-generation sequencing. The sequencing data from each replicate for each region should be aligned to either the full reference genome or to a locus-specific (amplicon) reference genome for analysis by 'rgenie'.