SCAFE: a software suite for analysis of transcribed cis-regulatory elements in single cells

Area of Science:

• Genomics
• Computational Biology
• Molecular Biology

Background:

• Cell type-specific cis-regulatory element (CRE) activity is crucial for gene regulation and disease understanding.
• Single-cell RNA 5'end sequencing (sc-end5-seq) measures transcribed CREs (tCREs) via transcription start sites (TSS), but artifactual TSS hinder accurate discovery.

Purpose of the Study:

• To develop a robust computational tool for de novo identification and annotation of tCREs from sc-end5-seq data.
• To overcome limitations of artifactual TSS in sc-end5-seq data for tCRE discovery.

Main Methods:

• Developed SCAFE (Single-Cell Analysis of Five-prime Ends), a software suite processing sc-end5-seq data.
• Employed multiple logistic regression to identify TSS clusters and annotate tCREs.
• Generated a tCRE-by-cell count matrix for downstream analyses.

Main Results:

• SCAFE effectively identifies TSS clusters and annotates tCREs from sc-end5-seq data.
• The software provides a tCRE-by-cell count matrix for advanced analyses.
• SCAFE offers flexible tools for independent or workflow-based execution.

Conclusions:

• SCAFE enhances the utility of sc-end5-seq for de novo discovery of transcribed cis-regulatory elements.
• The developed software facilitates deeper insights into gene regulation at single-cell resolution.
• SCAFE is a valuable resource for researchers studying gene regulation and disease predisposition.