InPAS: An R/Bioconductor Package for Identifying Novel Polyadenylation Sites and Alternative Polyadenylation from...

Area of Science:

• Genomics
• Molecular Biology
• Bioinformatics

Background:

• Alternative cleavage and polyadenylation (APA) is a key post-transcriptional gene regulation mechanism.
• APA increases transcriptome and proteome diversity but remains poorly understood due to experimental limitations.
• RNA sequencing (RNA-seq) data offers a powerful resource for identifying and quantifying APA events.

Purpose of the Study:

• To develop an accurate and versatile R/Bioconductor package for identifying and quantifying APA events from RNA-seq data.
• To enable the detection of both novel and known cleavage and polyadenylation sites (CPSs).
• To facilitate the analysis of APA events across various experimental designs and eukaryotic systems.

Main Methods:

• Development of InPAS (Identification of Novel alternative PolyAdenylation Sites), an R/Bioconductor package.
• Utilizing a naïve Bayes classifier based on flanking sequence features to fine-tune CPS positions.
• Employing linear models for APA event identification in complex experimental designs.
• Benchmarking InPAS against leading tools using simulated and experimental RNA-seq data with matched 3'-end RNA-seq data.

Main Results:

• InPAS accurately identifies novel and known CPSs and quantifies APA events.
• The package outperforms existing tools in precision, sensitivity, and specificity.
• InPAS demonstrates scalability and versatility across large, diverse RNA-seq datasets.
• The tool effectively analyzes APA events from complex experimental designs.

Conclusions:

• InPAS is an efficient and robust tool for APA event identification and quantification using conventional RNA-seq data.
• Its versatility supports APA regulation exploration across diverse eukaryotic systems and experimental designs.
• InPAS is expected to advance APA research, deepen understanding of gene regulation, and aid in biomarker/therapeutic discovery.