TY - JOUR A1 - Lee, Dongwon A1 - Kapoor, Ashish A1 - Lee, Changhee A1 - Mudgett, Michael A1 - Beer, Michael A. A1 - Chakravarti, Aravinda T1 - Sequence-based correction of barcode bias in massively parallel reporter assays Y1 - 2021/09/01 JF - Genome Research JO - Genome Research SP - 1638 EP - 1645 DO - 10.1101/gr.268599.120 VL - 31 IS - 9 UR - http://genome.cshlp.org/content/31/9/1638.abstract N2 - Massively parallel reporter assays (MPRAs) are a high-throughput method for evaluating in vitro activities of thousands of candidate cis-regulatory elements (CREs). In these assays, candidate sequences are cloned upstream or downstream from a reporter gene tagged by unique DNA sequences. However, tag sequences may themselves affect reporter gene expression and lead to major potential biases in the measured cis-regulatory activity. Here, we present a sequence-based method for correcting tag-sequence-specific effects and show that our method can significantly reduce this source of variation and improve the identification of functional regulatory variants by MPRAs. We also show that our model captures sequence features associated with post-transcriptional regulation of mRNA. Thus, this new method helps not only to improve detection of regulatory signals in MPRA experiments but also to design better MPRA protocols. ER -