GPS™ (Guide Positioning Sequencing)

GPS™ (Guide Positioning Sequencing)

A Whole-Genome DNA Methylation Platform with Unmatched Coverage and Clinical Translation Power

Overview

Guide Positioning Sequencing (GPS™) is a next-generation whole-genome DNA methylation sequencing technology designed to overcome the fundamental limitations of traditional bisulfite-based approaches.

Unlike conventional Whole Genome Bisulfite Sequencing (WGBS), GPS achieves near-complete methylome coverage while simultaneously preserving genomic variation information. This dual capability enables both comprehensive epigenetic profiling and accurate mutation detection within a single workflow.

GPS serves as the foundational discovery engine behind pan-cancer methylation marker development and full-lifecycle cancer monitoring solutions.

The Problem with Conventional Methylation Sequencing

Whole Genome Bisulfite Sequencing (WGBS) is widely used but presents significant limitations:

  • Practical CpG coverage limited to ~50%

  • Degradation of sequence information during bisulfite conversion

  • Reduced SNV detection accuracy

  • High sequencing depth requirements

  • Heavy bioinformatics burden

These constraints limit biomarker discovery depth and clinical translation efficiency.

GPS

The GPS Breakthrough

1. Near-Complete Methylome Coverage

Platform

Coverage Rate

Detection Range

Illumina 850K

3%

CpG islands/promoters

RRBS

15%

CpG islands + enhancers

WGBS

50%

Whole genome

GPS

96%

Whole genome

This means:

  • Nearly complete methylome representation

  • Minimal blind spots

  • Superior biomarker discovery depth

2. Simultaneous Methylation + Variant Detection

GPS preserves genomic sequence integrity and supports robust mutation analysis.

Metric

GPS

WGBS

SNVs detected

127,722

82,498

SNVs overlapping dbSNP

126,089

45,604

Overlap percentage

98.7%

55.3%

  • GPS detects significantly more SNVs

  • GPS achieves 98.7% concordance with dbSNP, nearly double WGBS

This is critical: GPS does not sacrifice mutation detection accuracy while profiling methylation. WGBS partially degrades sequence information due to bisulfite conversion. GPS preserves it.

3. High-Efficiency Library Architecture

GPS incorporates:

  • An innovative library construction system

  • A multi-dimensional bioinformatics architecture

  • Systematic genome-wide epigenetic marker exploration

This design reduces redundancy while increasing signal precision, making it both scientifically rigorous and clinically scalable.

4. From Discovery to Clinical Application

GPS is not merely a sequencing method.

It is the engine that enabled the development of: TAGMe®, Tumor-Aligned General Methylated Epiprobe, A panoramic pan-cancer methylation marker database built on whole-genome GPS profiling.

TAGMe markers exhibit:

  • All-or-none methylation patterns

  • Malignancy specificity

  • Earlier alteration than pathological changes

This binary switching behavior enhances signal clarity in liquid biopsy applications and significantly improves diagnostic sensitivity.

Core Advantages of GPS™

✔ 96% whole-genome CpG coverage

✔ 98.7% SNV concordance

✔ Simultaneous methylation and genomic variant profiling

✔ Superior marker discovery depth

✔ Binary cancer-specific methylation signatures

✔ Scalable for population screening and longitudinal monitoring

Technology Positioning

GPS™ is a whole-genome methylation discovery and translation platform that combines depth, accuracy, and efficiency—enabling next-generation cancer detection, monitoring, and precision oncology applications.

Reference: Li J et al. Guide Positioning Sequencing identifies aberrant DNA methylation patterns that alter cell identity and tumor-immune surveillance networks. Genome Res. 2019 Feb;29(2):270-280.