Telogator: a method for reporting chromosome-specific telomere lengths from long reads

Area of Science:

• Genomics
• Molecular Biology
• Bioinformatics

Background:

• Telomeres, repetitive DNA at chromosome ends, shorten with cell division, acting as a biological clock.
• Abnormal telomere length is linked to aging, cancer, and various diseases.
• Current methods often report average telomere length, missing chromosome-specific variations crucial for disease diagnostics.

Purpose of the Study:

• To introduce Telogator, a novel method for determining chromosome-specific telomere length.
• To evaluate Telogator's performance with simulated and real long-read sequencing data.
• To assess Telogator's utility in identifying subtelomere rearrangements.

Main Methods:

• Development of Telogator, a Python-based tool for analyzing long-read sequencing data.
• Simulation of sequencing data to test Telogator's sensitivity across various read lengths and error rates.
• Application of Telogator to 10 germline samples and comparison with short-read sequencing methods.

Main Results:

• Telogator accurately detects chromosome-specific telomere length in simulated data.
• High correlation observed between Telogator's average telomere length and traditional short-read methods.
• Identification of minimum read lengths required for accurate telomere/subtelomere boundary anchoring.

Conclusions:

• Telogator provides a sensitive and accurate method for chromosome-specific telomere length analysis from long-read sequencing.
• This approach enhances the potential for discovering disease biomarkers associated with specific telomere aberrations.
• Telogator facilitates the study of subtelomere structural variations.