Assistant Professor, Psychiatry and Preventive Medicine; Member, Zilkha Neurogenetic Institute and Norris Comprehensive Cancer Center
- Bioinformatics approaches for high-throughput sequencing data
- Genomic analysis of brain disorders
Research Overview1. Develop bioinformatics and computational biology methods to handle high-throughput genomics data sets, especially next-generation sequencing data. Previously, we have worked on SNP arrays and developed the PennCNV software for identifying copy number variations (CNVs) and the GenGen software for pathway-based association tests. Recently, we focused on whole-genome and whole-exome sequencing data, and developed the ANNOVAR software for functional annotation of genetic variants. With DNA and RNA sequencing data, we are developing methods to identify genetic variants (SNPs and CNVs), annotate variants, impute variants, infer expression level, identify somatic mutations, and perform association tests on genes, genomic regions and biological pathways.
2. Apply genomic approaches to a variety of brain disorders, especially brain cancer and neurodevelopmental diseases. I am currently collaborating with several colleagues at USC to examine brain disorders using high-throughput genomics approaches. For example, neurodevelopmental and neuropsychiatric diseases may result from perturbations of the nervous system, but it is extremely difficult to manipulate or interrogate this system in vivo in humans. Together with colleagues at the USC Broad CIRM center, we are establishing a stem cell model to identify genetic networks that link genetic risk to functional understanding of developmental processes. More importantly, the cellular system may be expanded to determine the functional impact of genetic lesions in other human diseases, or be used for personalized disease characterization and for optimization of therapeutic strategies. We are also interested in identifying genetic factors responsible for malignant transformation of meningioma and other brain tumors. Meningiomas are the most frequently diagnosed primary brain tumors, and can be broadly classified as benign versus anaplastic (malignant). The malignant tumors constitute ~3% of all meningiomas. However, little is known on what genes cause malignant transformation, and this will ultimately delay the development of effective treatment or prognosis strategies. Together with several colleagues at the Department of Neurosurgery, we will use high-throughput DNA and RNA sequencing approaches to identify somatic mutations, copy number alternations, fusion genes and splicing isoforms that make meningiomas become malignant, and test the therapeutic potential of targeted knockdown of gain-of-function mutations.
Gao F, Shi L, Russin J, Zeng L, Chang X, He S, Chen TC, Giannotta SL, Weisenberger DJ, Zada G, Mack WJ, Wang K. DNA Methylation in the Malignant Transformation of Meningiomas. PLoS ONE, 8:e54114, 2013 -PubMed
Chen GK, Wang K, Stram AH, Sobel EM, Lange K. Mendel-GPU: Haplotyping and genotype imputation on Graphics Processing Units. Bioinformatics, in press, 2012 -PubMed
Levinson DF, Shi J, Wang K, Oh S, Riley B, Pulver AE, Wildenauer DB, Laurent C, Mowry BJ, Gejman PV, Owen MJ, Kendler KS, Nestadt G, Schwab SG, Mallet J, Nertney D, Sanders AR, Williams NM, Wormley B, Lasseter VK, Albus M, Godard-Bauché S, Alexander M, Duan J, O'Donovan MC, Walsh D, O'Neill A, Papadimitriou GN, Dikeos D, Maier W, Lerer B, Campion D, Cohen D, Jay M, Fanous A, Eichhammer P, Silverman JM, Norton N, Zhang N, Hakonarson H, Gao C, Citri A, Hansen M, Ripke S, Dudbridge F, Holmans PA; The Schizophrenia Psychiatric GWAS Consortium. American Journal of Psychiatry. 169:963-973, 2012 -PubMed
Lyon GJ, Wang K. Identifying disease mutations in genomic medicine settings: current challenges and how to accelerate progress. Genome Medicine, 4:58, 2012 -PubMed
Qiu S, Luo S, Evgrafov O, Li R, Schroth GP, Levitt P, Knowles JA, Wang K. Single-neuron RNA-Seq: technical feasibility and reproducibility. Frontiers in Genetics, 3:124, 2012 -PubMed
Chang X, Wang K. wANNOVAR: annotating genetic variants for personal genomes via the web. Journal of Medical Genetics. 49:433-436, 2012 -PubMed
Lyon GJ, Jiang T, Van Wijk R, Wang W, Bodily P, Xing J, Tian L, Robison R, Clement M, Yang L, Zhang P, Liu Y, Moore B, Glessner J, Elia J, Reimherr F, van Solinge W, Yandell M, Hakonarson H, Wang J, Johnson WE, Wei Z, Wang K. Exome Sequencing and Unrelated Findings in the context of Complex Disease Research: Ethical and Clinical Implications. Discovery Medicine, 12:41-55, 2011 -PubMed -Link
Pham MH, Zada G, Mosich GM, Chen TC, Giannotta SL, Wang K, Mack WJ. Molecular Genetics of Meningiomas: A Systematic Review of the Current Literature and Potential Basis for Future Treatment Paradigms. Neurosurgical Focus, 30:e7, 2011 -PubMed