Abstract
Negative regulatory elements (NREs) down-regulate gene expression by inhibiting the activities of promoters or enhancers. The repressing activity of NREs can be measured globally by massively parallel reporter assays (MPRAs). However, most existing algorithms are designed for the statistical detection of positively enriched signals in MPRA datasets. To identify reduced signals in MPRA experiments, we designed a NRE identification program, fast-NR, by integrating the count and graphic features of sequenced reads to detect NREs using datasets generated by experiments of self-transcribing active regulatory region sequencing (STARR-seq). Fast-NR identified hundreds of silencers in human K562 cells that can be validated by independent methods.
Highlights
Eukaryotic gene expression is tightly controlled by various types of cis-regulatory elements (CREs) that are different in regulatory function, genetic, and epigenetic characteristics (Maston et al, 2006)
We provide a program Fast-NR that is designed for the identification of silencers using STARR-seqgenerated datasets by integrating the sequenced read count and signal shape features which are considered in the design of many ChIP-seq peak callers including Polyapeak, PICS, and CLC (Thomas et al, 2017; Hower et al, 2011; Cremona et al, 2019; Yan et al, 2020) (Zhang et al, 2011; Wu and Ji, 2014; Strino and Lappe, 2016)
We simulated a pair of STARR-seq datasets to test the Negative regulatory elements (NREs) identification powers of Fast-NR and other methods including csaw (Lun and Smyth, 2016), MEDIPS (Lienhard et al, 2014), PePr (Zhang et al, 2014), and CRADLE (Kim et al, 2021) using default parameters
Summary
Eukaryotic gene expression is tightly controlled by various types of cis-regulatory elements (CREs) that are different in regulatory function, genetic, and epigenetic characteristics (Maston et al, 2006). Potential silencers were predicted in cell lines (Doni Jayavelu et al, 2020) by gkmSVM which utilizes sequence features of known silencers (Ghandi et al, 2016). Genomic sequences of regulatory activity can be systematically assessed by STARR-seq, a widely used MPRA method initially designed for enhancer identification (Melnikov et al, 2012; Arnold et al, 2013; Crocker and Stern, 2013; Gisselbrecht et al, 2013; Mogno et al, 2013; Vanhille et al, 2015; Wang et al, 2018; Sun et al, 2019).
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
