Our group focus on application of computational biology and systems biology methods to understand the mechanisms of human complex diseases.

I) Genetic mutations mediated signaling network perturbations

How cancer-associated genetic variants impair protein activities in the context of signaling pathways remains mostly undetermined. Although a few renowned genetic variants are well characterized, functional information is missing for the majority variants. The disease-associated alleles that perturb distinct protein activities rather than grossly affecting folding and stability are relatively widespread. Here, we try to develop computational method to identify the genetic variants that perturbed the human signaling networks/pathways, including protein-protein network, protein-DNA, protein-RNA network, as well as noncoding RNA related networks.

II) Functional analysis of non-coding genetic variants

Whole-genome sequencing has revealed a large number of genetic variants that are associated with various types of tumors. The majority of the discovered genetic variants are located in noncoding regions of the human genome. These mutations affect gene expression to promote tumorigenesis via a wide range of mechanisms. One of the biggest challenges of human genetics is to identify causal mutations and to distinguish them from passengers. Understanding these mutations might unravel novel mechanisms underlying human cancers and provide new tumor-specific targets. Our group focused on developing computational methods for identification of non-coding causal mutations and investigation of varied modes of their action.

III) Regulatory network analysis in human complex diseases

Given the functional dependencies between the molecular components (DNA, RNA and proteins), human cancer is rarely a consequence of an abnormality in a single gene, but reflects the perturbations of the complex regulatory network. We aim to develop tools for analysis of biological network and offer a platform to explore systematically not only the molecular complexity of a particular disease, but also reveal the molecular relationships among distinct phenotypes.

IV) Systematical analysis of human immunome in cancer

Evidence has been accumulating that the immune system can recognise and reject tumours. The goal of tumour immunology has been to understand the components of the immune system that are important for tumour immunosurveillance and tumour rejection. Our group aim to systematical analysis of human immunome across cancer types to identify the critical gene, miRNA or lncRNAs for human immune therapy.

V) Computational epigenetics in human cancer

The potential mechanisms for gene misregulation in cancer involve both genetic mutations (genetic instability) and epigenetic modifications (such as DNA methylation, histone modifications and noncoding RNA regulation) that disrupt the function of genes, including tumor suppressor and oncogenes, as well as other genes related to cancer. We aim to develop computation tools, method to systematically analyze the perturbed pattern of epigenetic modifications in various types of cancer.