Computational Epigenetics

Bioinformatics for DNA methylation: The Computational Epigenetics Lab develops computational methods for DNA methylation assay of the next generation. The team also creates novel analytics to support technologies that integrate DNA methylation, genetic variation, chromatin accessibility and conformation.

Multi-omics data analysis for biological discovery: The Computational Epigenetics Lab does integrative data analysis to understand how cells translate epigenetic information into transcriptional regulation and eventually into phenotypical manifestation. The team focuses on leveraging DNA methylation as a robust readout of the chromatin state and cell identity.

Biomarkers discovery for medical applications: The Computational Epigenetics Lab develops biomarkers and diagnostic methods to aid translational research of childhood disease, including pediatric malignancies, developmental abnormalities, cognitive deficits, and infectious disease.

Project Highlights

• Highly proliferative tissue such as cancer is known for having undergone DNA methylation loss in adult humans. Through analyzing hundreds of human and mice methylomes, Dr. Zhou and his colleagues provided evidences to support mitotic division as the primary driving force of this DNA methylation attrition (Nature Genetics, 2018).
• Infinium microarray has been the primary workhorse of DNA methylation assay. Dr. Zhou and his colleagues comprehensively characterized this array and identified its novel usage (Nucleic Acids Res, 2017). The team developed critical statistical methods that lower Type-I error rate in signal detection calling of this array (Nucleic Acids Res, 2018).
• DNA methylation hypomethylating agent has been proposed as an effective adjuvant therapeutics for cancer immunotherapy. Dr. Zhou and his colleagues have performed data analysis and cell experiments to investigate DNMTi-ascorbate combination treatment for leukemia and MDS patients (PNAS, 2016).
• Ambiguity in variant annotation has been hampering the implementation of precision medicine. Dr. Zhou developed a fuzzy searching algorithm that allows scientists to process and reverse-inference the genomic variants based on isoform-specific notations (Nature Methods, 2015).
• DNA methylation is involved in genomic imprinting and is usually subject to strong purifying selection in the human population. Dr. Zhou and his colleagues identified nc886 genomic imprinting as a prominent example of polymorphic imprinting and linked its imprinting status to multiple human disease phenotypes (PNAS, 2018).