Computational systems biology  
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Research

Causal Pathways from Genotype to Phenotype

Elucidating causal pathways bridging genotype and phenotype is one of the fundamental challenges for genetic and genomic research. Gene variants that control phenotypes are typically discovered by combined linkage analysis and molecular validation. However, these genotype-phenotype associations do not expose the underlying causal pathways through which gene variants operate on phenotypes. We are exploring genomic and computational approaches to uncover the causal pathways through which genetic loci influence phenotypes and predict the effects of genetic and transcriptional variations/interventions on gene expression and physiological/behavioral phenotypes of individuals with different genetic backgrounds. We believe research towards this direction will ultimately lead to the development of the computational methods that enable predictive genetics and medicine.

Functional Effects of Genetic and Somatic mutations

Understanding the functional impacts of genetic and somatic mutations will provide a basis for assessing disease mechanism and designing individualized therapy. We have developed machine learning algorithms for predicting the functional effects of coding SNPs. We have also developed web-based platforms and databases for analyzing the genetic and somatic mutations in noncoding genomic regions such as microRNAs and their target sites.

CTCF binding sites and genome organization

CCCTC-binding factor (CTCF) is a versatile transcription regulator. CTCF binds to different DNA sequences through combinatorial use of 11-zinc fingers, and shows distinct functions (transcription activation/repression and chromatin insulation) depending on the biological context. CTCF also plays a crucial role in the global organization of chromatic architecture. We have developed the CTCF binding site database, a comprehensive collection of experimentally determined and computationally predicted CTCF binding sites (CTCFBS). The database is designed to facilitate the studies on CTCFBS as insulators and their roles in demarcating functional genomic domains.