Somatic MEIs can be detected from bulk tissue, PCR amplicons generated from sorted-cell fractions, or single-cell WGA DNA using split-read and paired-end information (e.g., one paired-end read may map to the reference genome, whereas another may map to a MEI) (91, 92). Detecting low-frequency MEIs with fewer supporting reads requires careful bioinformatic analyses that can distinguish signal from noise, followed by experimental validation with orthogonal methods (14, 93). The analysis of single-cell data remains challenging due to the presence of chimeras generated during WGA (14, 16, 94); thus, care must be taken in calling MEIs.
