Applying methylation haplotype analysis to cell-free DNA

DNA methylation has once been called the '5th DNA base' due to its importance in gene regulation, and has been studied for decades. With the advent of next-generation sequencing (NGS) methylation has been studied on a genome-wide level, an expensive process requiring both generating sequence data and analyzing sequence data many orders of magnitude higher than what a typical clinical laboratory can handle.

Targeted methylation approaches have historically not been developed due to technical hurdles. Singlera announces a unique approach, examining methylation haplotypes (adjacent methylation sites on the same contiguous strand of DNA) from cell-free DNA as a method for cancer biomarker detection.

By using a highly specific and targeted methylation enrichment method, both the overall sample input requirement is lowered and the overall amount of sequencing necessary for excellent sensitivity is reduced.

  • Empirical Classifier – Derived from over 20,000 methylation haplotypes and 10 years of volunteer samples

  • High Sensitivity and Specificity – Analytical results show greater than 97% sensitivity and over 99% specificity *

  • Early Detection of Cancer – Data suggests detection of cancer four years before earliest conventional diagnosis

* The ColonES assay sensitivity for CRC Stage I in clinical samples

Efficient biomarker screening technology coupled with fast custom targeted methylation haplotyping and proprietary bioinformatics analysis.


Take a closer look at our leading-edge research in methylation and its role in disease in top research publications.


Learn how Singlera’s methylation haplotyping technology can give better cancer biomarker sensitivity.

Available Assays

Learn more about our two assays, PanSeer to detect several cancer types, and ColonES that specifically detects colorectal cancer markers with high sensitivity and specificity.

Collaboration and Co-Development

Do you see promise in our methylation haplotype approach? Do you think it could complement work you are doing in developing in-vitro diagnostics for cancer?


Sensitivity of PanSeer 4 years pre-conventional diagnosis


Specificity of PanSeer across 498 healthy individuals


Sensitivity of ColonES in Stage I Colorectal cancer


Specificity of ColonES in healthy individuals


Taizhou China volunteers
Years volunteers monitored
Number of methylation haplotype markers used in ColonES
Hours from DNA to sequencer-ready library


Three of Five Scientific Co-Founders of Singlera Genomics

Yuan Gao, CEO and Co-Founder of Singlera Genomics

Yuan (Gary) Gao Ph.D.

Chairman and Co-Founder


Dr. Yuan Gao is an innovator of translational technologies for next generation sequencing, non-invasive prenatal testing (NIPT), DNA methylation sequencing, and digital information storage in DNA. He is also a founder and President of Med Data Quest, Inc., developing clinical natural language processing and machine learning tools to aid precision medicine. He has a Bachelor of Bioscience from Beijing University, a Ph.D. in Computer Science from the Memphis University, completed his post-doctoral training with George Church at Harvard University, and most recently was an Associate Professor at Johns Hopkins University.

Dr. Kun Zhang Co-Founder Singlera Genomics

Kun Zhang, Ph.D.

Co-founder and Scientific Advisor


Dr. Zhang is recognized for multiple achievements including single-cell whole genome sequencing, targeted DNA methylation sequencing, somatic genomic instability in induced pluripotent stem cells, Microwell Displacement Amplification System (MIDAS), and methylation haplotyping technology for non-invasive detection of ctDNA. Dr. Zhang holds a Ph.D. in Human and Molecular Genetics from the University of Texas Houston, completed his post-doctoral training with George Church at Harvard Medical School, and has a B.S. in Biophysics from Fudan University. He currently is a Professor in the Dept of Bioengineering at UCSD.

Dr. Rui Liu CTO Singlera Genomics

Rui Liu,Ph.D.

Co-Founder, Chief Technology Officer


Dr. Liu first demonstrated ultra-low input RNA sequencing and whole-genome bisulfite sequencing in germ cells with Dr. Yi Zhang at Harvard University. She then developed large-scale single-cell RNA sequencing technology for the NIH Single Cell Analysis Program (coordinating laboratories at UCSD, Scripps Inst. and Illumina Inc.) to systematically map single-neuron RNA expression. Dr. Liu received a Ph.D. in Genetics from the Univ of Pennsylvania and did her post-doctoral work with Dr. Kun Zhang at UCSD. She also has a Bachelor’s degree in Clinical Medicine from Peking University and a B.S. in Biophysics from Fudan University.

Discover The Future

At the leading edge of biology and assay technology, Singlera Genomics uses a new biomarker type called ctmDNA (circulating tumor methylated DNA) to peer into the future.