mountainClimber

mountainClimber detects change points in RNA-Seq read coverage to identify alternative transcription start (ATS) and alternative polyadenylation (APA) sites and map transcriptional end diversity.

Key Features:

• De Novo Cumulative-Sum-Based Approach: Uses a cumulative-sum-based method to pinpoint change points in read coverage corresponding to potential ATS or APA sites.
• Single Sample Analysis: Operates on a single RNA-Seq sample to identify multiple ATS and APA sites across the transcriptome without requiring paired data.
• Comprehensive Detection: Detects multiple alternative sites throughout transcripts to provide a detailed map of transcriptional diversity within a sample.

Scientific Applications:

• Large-scale tissue profiling (GTEx): Applied to 2,342 GTEx samples across 36 tissues and 215 individuals, revealing tissue type as a primary factor influencing transcript end variation and reporting that 75% of genes exhibit differential APA and 65% exhibit differential ATS across tissues.
• Tissue-specific UTR characterization (testis): Identified that testis tissues exhibit longer 5' UTRs and shorter 3' UTRs, often in genes associated with testis-specific functions.

Methodology:

Detection of change points using a cumulative-sum approach to identify significant changes in RNA-Seq read coverage corresponding to ATS or APA sites; single-sample analysis to identify multiple alternative sites within one RNA-Seq sample; comprehensive mapping of multiple alternative sites across transcripts.