BCREval

BCREval estimates the bisulfite conversion ratio (BCR) in whole genome shotgun bisulfite sequencing (WGSBS/WGBS, also BS-seq) by calculating the unconverted rate (UCR) from telomeric repetitive DNA as a native spike-in control to support accurate DNA methylation analysis.

Key Features:

• UCR estimation: Calculates the unconverted rate (UCR) to infer bisulfite conversion efficiency.
• Telomeric native spike-in: Leverages telomeric repetitive DNA as an internal/native spike-in control for conversion assessment.
• Binomial modeling: Models non-CpG DNA methylation at telomeres using a binomial model (observed ratio < 0.4%).
• BCR reporting: Reports bisulfite conversion ratio (BCR) metrics derived from telomeric UCR estimates.
• Public WGBS validation: Validated on public WGBS datasets showing most assays exceed 99.5% conversion efficiency.
• Comparative performance: Includes comparative analysis versus Bismark indicating faster and more efficient evaluation.

Scientific Applications:

• WGBS quality control: Provides QC metrics for whole genome bisulfite sequencing and WGSBS datasets.
• Conversion efficiency assessment: Quantifies bisulfite conversion to identify incomplete conversion that can lead to false positive methylation calls.
• Methylation data validation: Supports validation of DNA methylation measurements in BS-seq experiments by estimating BCR/UCR.
• Pipeline integration: Can be used to incorporate conversion-efficiency checks into WGBS data analysis pipelines.

Methodology:

Estimates UCR by leveraging telomeric repetitive DNA as a native spike-in control, models non-CpG methylation at telomeres with a binomial model (ratio < 0.4%), and has been validated on public WGBS datasets with comparative analysis against Bismark.