Bioinformatics Methodology Development and Applications

science park maggie

We develop statistical genetic methods for accurate genetic association tests and complex disease classification towards generating clinical impact. Working data types include whole genome and exome sequencing data, GWAS, transcriptome, methylation genome, and microbiome. Particularly, we use bioinformatics modelling on capturing the pattern of gene sequence evolution. Our solutions for influenza vaccine has led to proprietary technologies, patents filing, and the founding of a start-up company in the Hong Kong Science and Technology Park (HKSTP). Our research is organized into the following four topics:

  1. Statistical genetic methods for epistasis and association testing in the human genome
  2. Viral genetics
  3. Disease prediction using omics data  
  4. Synergic collaborations in clinical and biomedical sciences  


1.  Statistical genetic methods for epistasis and association testing in the human genome

Genetic epistasis is an important phenomenon in molecular biology, yet its effect is challenging to capture quantitatively in the genome. We devised novel statistical methods to model interaction pattern, enabling efficient evaluation of potential epistasis mechanisms. We balance theoretical rigorousness and practical scalability to exploit pattern in the data fully. This work demonstrated our strength to design new statistical and computational methods to solve real problems in big data analytics. In whole genome/exome sequencing data analysis, testing power is generally low even using rare variant-specific methods. According to variants distribution in a gene, We proposed to enhance the statistical power by optimizing the testing region. The method delicately controls for multiple testing issues, and its application enabled the identification of new biomarkers for the Crohn’s Disease. The development of this method is a combination of multidisciplinary techniques, including statistics, computer science, and human genetics. 

Selected publications:

Maggie Haitian Wang, Rui Sun, Junfeng Guo, Haoyi Weng, Jack Lee, Inchi Hu, Pak Sham and Benny C.Y. Zee (2016). A fast and powerful W-test for pairwise epistasis testing. Nucleic Acids Research. IF = 11.561, 10/293 in Biochemistry & Molecular Biology Science. Doi: 10.1093/nar/gkw347

Maggie Haitian Wang, Haoyi Weng, Rui Sun, Jack Lee, William Ka Kei Wu, Ka Chun Chong, Benny Chung-Ying Zee (2017) A Zoom-Focus Algorithm (ZFA) to locate the optimal testing region for rare variant association tests. Bioinformatics. IF=5.481. Rank 3/59 in Mathematics and Computational Biology.

Rui Sun, Haoyi Weng, Inchi Hu, Junfeng Guo, William K.K. Wu, Benny Chung-Ying Zee, Maggie Haitian Wang (2016) A W-test collapsing method for rare variant association testing in exome sequencing data. Genetic Epidemiology. 2016 Nov;40(7):591-6. IF = 2.116. DOI: 10.1002/gepi.22000.

Rui Sun, Xiaoxuan Xia, Ka Chun Chong, Benny Chung-Ying Zee, William Ka Kei Wu, Maggie Haitian Wang (2019) wtest: an integrated R package for genetic epistasis testing, BMC Medical Genomics. IF= 2.632 Doi:

Maggie Haitian Wang, Heather Cordell, Kristel Van Steen (2019) Statistical Methods for Genome-wide Association Studies. Seminars in Cancer Biology. 2019 April. Rank 13/223 in Oncology. IF = 10.198 Doi: 10.1016/j.semcancer.2018.04.008

William KK Wu, Rui Sun, Tao Zuo, Yuanyuan Tian, Zhirong Zeng, Jeffery Ho, Justin CY Wu, Francis KL Chan, Matthew TV Chan, Jun Yu, Joseph JY Sung, Sunny H Wong, Maggie H Wang, Siew C Ng* (2018) A novel susceptibility locus in MST 1 and gene‐gene interaction network for Crohn’s disease in the Chinese population. Journal of Cellular and Molecular Medicine. 2018 Apr;22(4):2368-77. Rank 25/133 in Medicine, Research & Experimental Science. IF = 4.302 Doi: 10.1111/jcmm.13530

Xiaoxuan Xia, Haoyi Weng, Rui Sun, Ka Chun Chong, Benny Chung Ying Zee, Maggie Haitian Wang Incorporating methylation genome information improves prediction accuracy for drug treatment responses. BMC Genetics. 2018 Sep;19(1):78. IF = 2.569 Doi: 10.1186/s12863-018-0644-5

Svetlana Cherlin, Maggie Haitian Wang, Heike Bickeböller, Rita M. Cantor (2018) Detecting Responses to Treatment with Fenofibrate in Pedigrees. BMC Genetics. 2018 Sep;19(1): p64. IF = 2.569 Doi: 10.1186/s12863-018-0652-5.

Maggie Haitian Wang, Billy Chang, Rui Sun, Inchi Hu, Marc Ka Chun Chong, Benny Chung Ying Zee (2017), A Stratified Polygenic Risk Prediction Model with Application on CAGI Bipolar Disorder Sequencing Data. Human Mutation. 2017 Sep;38(9):1235-9. Rank 24/171 in Genetics & Heredity Science. IF=5.359.


2.  Viral genetics

Since 2013, we have been intensively studied the viral genome of the influenza virus and other pathogens. This area of research aims to develop a more accurate vaccine for infectious diseases using improved design through bioinformatics. We capture the mutation pattern, genome interactions, antibody binding chemical properties, and 3D structures of the virus. More publications are coming under this topic.

Selected publications:

Shi Zhao, Jingzhi Lou, Lirong Cao, Zigui Chen, Renee WY Chan, Marc KC Chong, Benny CY Zee, Paul KS Chan, Maggie H Wang (2020) Quantifying the importance of the key sites on haemagglutinin in determining the selection advantage of influenza virus: using A/H3N2 as an example. Journal of Infection. (2020). IF = 5.099. Rank 19/286 in Infectious Diseases.

Chan MC, Wang MH, Chen Z, Hui DS, Kwok AK, Yeung AC, Liu KM, Yeoh YK, Lee N, Chan PK. Frequent Genetic Mismatch between Vaccine Strains and Circulating Seasonal Influenza Viruses, Hong Kong, China, 1996–2012. Emerging infectious diseases. 2018 Oct;24(10):1825. IF = 7.422. Rank 4/88 in Infectious Disease Doi: 10.3201/eid2410.180652  

Yaqing He, Linjie Zou, Marc Chong, Ruoting Men, Wenbo Xu, Hong Yang, Xiangjie Yao, Long Chen, Huixia Xian, Hailong Zhang, Min Luo, Jinquan Cheng, Hanwu Ma, Qianjin Feng, Yun Huang, Yujie Wang, Eng-kiong Yeoh, Benny Zee, Yuanping Zhou, Ming-Liang He and Maggie Haitian Wang (2016) Genetic Evolution of Human Enterovirus A71 Subgenotype C4 in Shenzhen, China, 1998-2013. Journal of Infection. 2016 Jun 1;72(6):731-7. Rank 14/88 in Infectious Diseases Science. IF = 4.603. Doi: 10.1016/j.jinf.2016.03.014.

Chunli Wu+, Maggie Haitian Wang+, Xing Lu, Ka Chun Chong, Jason He, Chun-Yip Yau, Mark Hui, Xiaowen Cheng, Li Yang, Benny Chung-Ying Zee, Renli Zhang, and Ming-Liang He (2016) Concurrent epidemics of influenza A/H3N2 and A/H1N1pdm in Southern China: a serial cross-sectional study. Journal of Infection. 2016 Mar; 72(3):369-76. Epub 2015 Dec 30. Rank 14/88 in Infectious Diseases Science. IF = 4.603 DOI: 10.1016/j.jinf.2015.12.013.


3.  Disease prediction using omics data

Prediction of disease outcome has clinical significance for precision medicine in terms of treatment selection and early intervention. Development along this line has led to our working paper on the Prism Vote method, and the patent Prediction Models Incorporating Stratification of Data (US Provisional Patent No. 62/915,459, Oct 2019), now being licensed for translation use in the commercial genetic testing market.

Selected Publications:

Maggie Haitian Wang, Shaw-Hwa Lo, Tian Zheng and Inchi Hu (2012) Interaction-based feature selection and classification for high-dimensional biological data. Bioinformatics. 2012 Sep 3;28(21):2834-42. Rank 3/59 in Mathematics and Computational Biology. IF=5.481. Doi: 10.1093/bioinformatics/bts531

Maggie Haitian Wang, Billy Chang, Rui Sun, Inchi Hu, Marc Ka Chun Chong, Benny Chung Ying Zee (2017), A Stratified Polygenic Risk Prediction Model with Application on CAGI Bipolar Disorder Sequencing Data. Human Mutation. IF=5.359. Rank 24/171 in Genetics & Heredity Science

Svetlana Cherlin, Maggie Haitian Wang, Heike Bickeböller, Rita M. Cantor (2018) Detecting Responses to Treatment with Fenofibrate in Pedigrees. BMC Genetics. 2018 Sep;19(1): p64. IF = 2.569 Doi: 10.1186/s12863-018-0652-5.

Maggie Haitian Wang, Kelvin Tsoi, Xin Lai, Marc Chong, Tian Zheng, Shaw-Hwa Lo, Benny Zee and Inchi Hu (2015). Two screening methods for genetic association study with application on psoriasis microarray data sets. IEEE International Congress on Big Data. 2015 Jun 27 (pp. 324-326). Doi: 10.1109/BigDataCongress.2015.55.

Maggie Haitian Wang, Steven YF Lau, Chloe Kwok, Ka Chun Chong, Maria Lai, Anthony HY Chung, Chung Shun Ho, Cheuk-Chun Szeto, Benny Chung-Ying Zee (2017). Estimation of clinical parameters of chronic kidney disease (CKD) by exhaled breath full-scan mass spectrometry data and Iterative PCA with Intensity Screening (IPS) algorithm. Doi: 10.1088/1752-7163/aa7635 Journal of Breath Research. IF=3.489. Rank 20/60 in Respiratory System Science. 

Maggie Haitian Wang, Ka Chun Chong, Hau Yin Chung, Malina Storer, John Pickering, Zoltan Endre, Steven Lau, Chloe Kwok, Maria Lai, Benny Zee (2016). Use of a Least Absolute Shrinkage and Selection Operator (LASSO) Model to Selected Ion Flow Tube Mass Spectrometry (SIFT-MS) Analysis of Exhaled Breath to Predict the Efficacy of Dialysis. Doi: 10.1088/1752-7155/10/4/046004


 4.   Synergic collaborations in clinical and biomedical sciences

Bioinformatics collaborations with biomedical and clinical scientists synergized our expertise in different areas. We characterize biological mechanisms through joint bioinformatics and laboratory experiments in various diseases. We also collaborated closely with clinicians in epidemiology study design and analysis.

Selected Publications:

Xiaoxuan Xia, William K.K. Wu, Sunny H. Wong, Dabin Liu, Thomas N.Y. Kwong, Geicho Nakatsu, Pearlly S. Yan, Yu-Ming Chuang, Michael W.Y. Chan, Olabisi O. Coker, Zigui Chen, Yun K. Yeoh, Liuyang Zhao, Xiansong Wang, Wing Y. Cheng, Matthew T.V. Chan, Paul K.S. Chan, Joseph J.Y. Sung, Maggie H Wang*, Jun Yu* (2020) (co-corresponding author) Bacteria pathogens drive host colonic epithelial cell promoter hypermethylation of tumour suppressor genes in colorectal cancer. Microbiome. IF=10.465, Rank 7/149 in Microbiology

Jin Shen, William K.K. Wu, Maggie H. Wang, Ka F. To, Yangchao Chen, Zhangang Xiao, May S.M. Li, Joanna H. Tong, Wei Kang, Lin Zhang, Lin Wang, Lan Lu, Ruby L.Y. Chan, Jun Yu, Francis K.L. Chan, Joseph J.Y. Sung, Alfred S.L. Cheng, Chi H. Cho (2014) Epigenetic silencing of miR-490-3p reactivates the chromatin remodeler SMARCD1 to promote Helicobacter pylori-induced gastric carcinogenesis. Cancer Research. 2015 Feb 15;75(4):754-65. Rank 17/223 in Oncology Science. IF=9.13. Doi: 10.1158/0008-5472.CAN-14-1301.

Li J, Ogorodova LM, Mahesh PA, Wang MH, Fedorova OS, Leung TF, Fernandez-Rivas M, Mills EC, Potts J, Kummeling I, Versteeg SA, van Ree R, Yazdanbakhsh M, Burney PGJ, Wong GWK. (2019). Comparative study of food allergies in children from China, India and Russia: The EuroPrevall-INCO surveys. 2019 Dec 16. Journal of Allergy and Clinical Immunology. IF= 13.258 Doi: 10.1016/j.jaip.2019.11.042.

XIE Chen; WANG Zhijun; WANG Charles; XU Jun; WEN Zhining; WANG Haitian; SHI Leming; CHOW S.s. Moses; HUANG Ying and ZUO Zhong. (2013) Utilization of Gene Expression Signature for Quality Control of Traditional Chinese Medicine Formula Si-Wu-Tang. The AAPS Journal. 2013 Jul 1;15(3):884-92. IF = 4.374 Doi: 10.1208/s12248-013-9491-5.