My main research interest is to develop novel sequencing methods for detection of DNA epigenetic modifications, which play important roles in a broad range of biological processes from gene regulation to normal development and are related to various diseases including cancer. Bisulphite sequencing has been the gold standard for DNA methylation analysis for decades. However, this harsh method degrades the majority of DNA and generates sequencing libraries with low complexity. Those drawbacks limit the applications on low-input samples and third generation long-read length sequencing, and lead to poor sequencing quality, low mapping rates, uneven genome coverage and increased sequencing cost. To overcome those problems, we have developed TET-Assisted Pyridine borane Sequencing (TAPS) for direct detection of 5-methylcytosine (5mC) and 5-hydroxymethylcytosine (5hmC) without affecting unmodified cytosine. This non-destructive method enables high-throughput sequencing with nanoscale input materials and preserves DNA over 10 kb long. I am currently focusing on developing derivative methods of TAPS for individual detection of 5mC and 5hmC and applying TAPS on single-cell epigenetics and third-generation sequencing platforms such as PacBio SMRT sequencing and Oxford Nanopore.
I completed both my BSc and PhD degrees at the College of Chemistry and Molecular Engineering, Peking University, focused on inhibition of nuclease enzymes using tailor-made nanoparticles. Then I received postdoctoral training at the Dana-Farber Cancer Institute, Harvard Medical School. It is there that I turned my attention to DNA methylation and developed a new method to detect low abundant aberrant DNA methylation in cancer. I joined Chunxiao Song’s group at Ludwig Institute for Cancer Research as a postdoc researcher in August 2017.
TAPS: A bisulfite-free, base-resolution and quantitative sequencing method for cytosine modifications
Liu Y. et al, (2019), CANCER RESEARCH, 79
Bisulfite-free direct detection of 5-methylcytosine and 5-hydroxymethylcytosine at base resolution.
Liu Y. et al, (2019), Nat Biotechnol, 37, 424 - 429
Bisulfite-free, Base-resolution, and Quantitative Sequencing of Cytosine Modifications
Liu Y. et al, (2018)
A specific DNA-nanoprobe for tracking the activities of human apurinic/apyrimidinic endonuclease 1 in living cells
Zhai J. et al, (2017), Nucleic Acids Research, 45, e45 - e45
Methylation-sensitive enrichment of minor DNA alleles using a double-strand DNA-specific nuclease.
Liu Y. et al, (2017), Nucleic Acids Res, 45