- Biomedical Sciences Graduate Program | Chongzhi Zang

Chongzhi Zang

Education

  • BS, Peking University
  • PhD, George Washington University
  • Postdoc, Harvard University

Contact

Research Interest(s)

Bioinformatics methodology development; Epigenetics and chromatin biology; Transcriptional regulation; Cancer genomics and epigenomics; Statistical methods for biomedical data integration; Theoretical and computational biophysics

Research Description

The research in my lab focuses on developing computational methodologies and integrative genomics approaches to study epigenetics and transcriptional regulation of gene expression in a variety of mammalian cell systems and human diseases such as cancer.

How gene expression is regulated in chromatin is a fundamental question in molecular biology. High-throughput technologies such as next-generation sequencing (NGS) have become powerful tools for studying gene regulation at the genomic scale. We conduct computational research that leverages these genomics technologies. Some research directions include:

1. Next-generation sequencing bioinformatics

We are interested in developing statistical methods and novel algorithms for analyzing massive data from next-generation sequencing (NGS) coupled with various assays for studying genomic chromatin profiles, such as ChIP-seq for transcription factor and histone mark profiling, ATAC-seq and DNase-seq for chromatin accessibility profiling, etc. As a pioneer in ChIP-seq bioinformatics, we developed SICER (Bioinformatics 2009), one of the most widely used methods for ChIP-seq data analysis with exceptional performance for board histone modification marks. We are developing novel statistical models and computational methods for analyzing DNase/ATAC-seq data and for studying chromatin dynamics.

2. Chromatin, epigenetics, and transcriptional regulation

Our ultimate goal is to understand the fundamental mechanisms in transcriptional regulation and the functions of chromatin. We characterized dozens of histone modifications and histone modifying enzymes at the genomic scale (Nat Genet 2008, Nat Genet 2009, Cell 2009, Cell Stem Cell 2009). Leveraging the large amount of publicly available ChIP-seq data, we developed MARGE (Genome Res 2016), a computational method to predict cis-regulatory profiles from differential expression gene sets using integrative learning approaches. We are specifically interested in studying functional enhancer regulation of gene expression in cancers.

3. Genomic data integration for chromatin dynamics and regulatory networks

High-dimensional genomic data analysis is challenging because of noises and biases in high-throughput experiments. We developed MANCIE (Nat Commun 2016), a method for bias correction and data integration of cross-platform genomic profiles on the same samples, using a Bayesian-supported principal component analysis (PCA)-based approach. We are interested in using statistical modeling and machine-learning approaches to integrate public genomic data for characterizing physical properties of mammalian epigenomes and dynamic interactions between chromatin and DNA in human cell systems.

Selected Publications

  • Severson E, Arnett K, Wang H, Zang C, Taing L, Liu H, Pear W, Shirley Liu X, Blacklow S, Aster J. Genome-wide identification and characterization of Notch transcription complex-binding sequence-paired sites in leukemia cells. Science signaling. 2017;10(477). PMID: 28465412
  • Mei S, Qin Q, Wu Q, Sun H, Zheng R, Zang C, Zhu M, Wu J, Shi X, Taing L, Liu T, Brown M, Meyer C, Liu X. Cistrome Data Browser: a data portal for ChIP-Seq and chromatin accessibility data in human and mouse. Nucleic acids research. 2016. PMID: 27789702
  • Qin Q, Mei S, Wu Q, Sun H, Li L, Taing L, Chen S, Li F, Liu T, Zang C, Xu H, Chen Y, Meyer C, Zhang Y, Brown M, Long H, Liu X. ChiLin: a comprehensive ChIP-seq and DNase-seq quality control and analysis pipeline. BMC bioinformatics. 2016;17(1): 404. PMID: 27716038 | PMCID: PMC5048594
  • Wang S, Zang C, Xiao T, Fan J, Mei S, Qin Q, Wu Q, Li X, Xu K, He H, Brown M, Meyer C, Liu X. Modeling cis-regulation with a compendium of genome-wide histone H3K27ac profiles. Genome research. 2016;26(10): 1417-1429. PMID: 27466232 | PMCID: PMC5052056
  • Zang C, Luyten A, Chen J, Liu X, Shivdasani R. NF-E2, FLI1 and RUNX1 collaborate at areas of dynamic chromatin to activate transcription in mature mouse megakaryocytes. Scientific reports. 2016;6 30255. PMID: 27457419 | PMCID: PMC4960521
  • Zang C, Wang T, Deng K, Li B, Hu S, Qin Q, Xiao T, Zhang S, Meyer C, He H, Brown M, Liu J, Xie Y, Liu X. High-dimensional genomic data bias correction and data integration using MANCIE. Nature communications. 2016;7 11305. PMID: 27072482 | PMCID: PMC4833864
  • Finucane H, Bulik-Sullivan B, Gusev A, Trynka G, Reshef Y, Loh P, Anttila V, Xu H, Zang C, Farh K, Ripke S, Day F, Purcell S, Stahl E, Lindstrom S, Perry J, Okada Y, Raychaudhuri S, Daly M, Patterson N, Neale B, Price A. Partitioning heritability by functional annotation using genome-wide association summary statistics. Nature genetics. 2015;47(11): 1228-35. PMID: 26414678 | PMCID: PMC4626285
  • Jiang P, Wang H, Li W, Zang C, Li B, Wong Y, Meyer C, Liu J, Aster J, Liu X. Network analysis of gene essentiality in functional genomics experiments. Genome biology. 2015;16 239. PMID: 26518695 | PMCID: PMC4627418
  • Xu H, Xu K, He H, Zang C, Chen C, Chen Y, Qin Q, Wang S, Wang C, Hu S, Li F, Long H, Brown M, Liu X. Integrative Analysis Reveals the Transcriptional Collaboration between EZH2 and E2F1 in the Regulation of Cancer-Related Gene Expression. Molecular cancer research : MCR. 2015;14(2): 163-72. PMID: 26659825 | PMCID: PMC4828727
  • Gusev A, Lee S, Trynka G, Finucane H, Vilhjálmsson B, Xu H, Zang C, Ripke S, Bulik-Sullivan B, Stahl E, Kähler A, Hultman C, Purcell S, McCarroll S, Daly M, Pasaniuc B, Sullivan P, Neale B, Wray N, Raychaudhuri S, Price A. Partitioning heritability of regulatory and cell-type-specific variants across 11 common diseases. American journal of human genetics. 2014;95(5): 535-52. PMID: 25439723 | PMCID: PMC4225595
  • Luyten A, Zang C, Liu X, Shivdasani R. Active enhancers are delineated de novo during hematopoiesis, with limited lineage fidelity among specified primary blood cells. Genes & development. 2014;28(16): 1827-39. PMID: 25128499 | PMCID: PMC4197967
  • Stoeck A, Lejnine S, Truong A, Pan L, Wang H, Zang C, Yuan J, Ware C, MacLean J, Garrett-Engele P, Kluk M, Laskey J, Haines B, Moskaluk C, Zawel L, Fawell S, Gilliland G, Zhang T, Kremer B, Knoechel B, Bernstein B, Pear W, Liu X, Aster J, Sathyanarayanan S. Discovery of biomarkers predictive of GSI response in triple-negative breast cancer and adenoid cystic carcinoma. Cancer discovery. 2014;4(10): 1154-67. PMID: 25104330 | PMCID: PMC4184927
  • Wang H, Zang C, Liu X, Aster J. The role of Notch receptors in transcriptional regulation. Journal of cellular physiology. 2014;230(5): 982-8. PMID: 25418913 | PMCID: PMC4442318
  • Yashiro-Ohtani Y, Wang H, Zang C, Arnett K, Bailis W, Ho Y, Knoechel B, Lanauze C, Louis L, Forsyth K, Chen S, Chung Y, Schug J, Blobel G, Liebhaber S, Bernstein B, Blacklow S, Liu X, Aster J, Pear W. Long-range enhancer activity determines Myc sensitivity to Notch inhibitors in T cell leukemia. Proceedings of the National Academy of Sciences of the United States of America. 2014;111(46): E4946-53. PMID: 25369933 | PMCID: PMC4246292
  • Zheng X, Zhao Q, Wu H, Li W, Wang H, Meyer C, Qin Q, Xu H, Zang C, Jiang P, Li F, Hou Y, He J, Wang J, Wang J, Zhang P, Zhang Y, Liu X. MethylPurify: tumor purity deconvolution and differential methylation detection from single tumor DNA methylomes. Genome biology. 2014;15(8): 419. PMID: 25103624 | PMCID: PMC4165374
  • He H, Meyer C, Hu S, Chen M, Zang C, Liu Y, Rao P, Fei T, Xu H, Long H, Liu X, Brown M. Refined DNase-seq protocol and data analysis reveals intrinsic bias in transcription factor footprint identification. Nature methods. 2013;11(1): 73-8. PMID: 24317252 | PMCID: PMC4018771
  • Wang H, Zang C, Taing L, Arnett K, Wong Y, Pear W, Blacklow S, Liu X, Aster J. NOTCH1-RBPJ complexes drive target gene expression through dynamic interactions with superenhancers. Proceedings of the National Academy of Sciences of the United States of America. 2013;111(2): 705-10. PMID: 24374627 | PMCID: PMC3896193
  • Wang S, Sun H, Ma J, Zang C, Wang C, Wang J, Tang Q, Meyer C, Zhang Y, Liu X. Target analysis by integration of transcriptome and ChIP-seq data with BETA. Nature protocols. 2013;8(12): 2502-15. PMID: 24263090 | PMCID: PMC4135175
  • Hao H, Kim D, Klocke B, Johnson K, Cui K, Gotoh N, Zang C, Gregorski J, Gieser L, Peng W, Fann Y, Seifert M, Zhao K, Swaroop A. Transcriptional regulation of rod photoreceptor homeostasis revealed by in vivo NRL targetome analysis. PLoS genetics. 2012;8(4): e1002649. PMID: 22511886 | PMCID: PMC3325202
  • Daniel J, Santos M, Wang Z, Zang C, Schwab K, Jankovic M, Filsuf D, Chen H, Gazumyan A, Yamane A, Cho Y, Sun H, Ge K, Peng W, Nussenzweig M, Casellas R, Dressler G, Zhao K, Nussenzweig A. PTIP promotes chromatin changes critical for immunoglobulin class switch recombination. Science (New York, N.Y.). 2010;329(5994): 917-23. PMID: 20671152 | PMCID: PMC3008398
  • Wei L, Vahedi G, Sun H, Watford W, Takatori H, Ramos H, Takahashi H, Liang J, Gutierrez-Cruz G, Zang C, Peng W, O'Shea J, Kanno Y. Discrete roles of STAT4 and STAT6 transcription factors in tuning epigenetic modifications and transcription during T helper cell differentiation. Immunity. 2010;32(6): 840-51. PMID: 20620946 | PMCID: PMC2904651
  • Araki Y, Wang Z, Zang C, Wood W, Schones D, Cui K, Roh T, Lhotsky B, Wersto R, Peng W, Becker K, Zhao K, Weng N. Genome-wide analysis of histone methylation reveals chromatin state-based regulation of gene transcription and function of memory CD8+ T cells. Immunity. 2009;30(6): 912-25. PMID: 19523850 | PMCID: PMC2709841
  • Cui K, Zang C, Roh T, Schones D, Childs R, Peng W, Zhao K. Chromatin signatures in multipotent human hematopoietic stem cells indicate the fate of bivalent genes during differentiation. Cell stem cell. 2009;4(1): 80-93. PMID: 19128795 | PMCID: PMC2785912
  • Jin C, Zang C, Wei G, Cui K, Peng W, Zhao K, Felsenfeld G. H3.3/H2A.Z double variant-containing nucleosomes mark 'nucleosome-free regions' of active promoters and other regulatory regions. Nature genetics. 2009;41(8): 941-5. PMID: 19633671 | PMCID: PMC3125718
  • Wang Z, Zang C, Cui K, Schones D, Barski A, Peng W, Zhao K. Genome-wide mapping of HATs and HDACs reveals distinct functions in active and inactive genes. Cell. 2009;138(5): 1019-31. PMID: 19698979 | PMCID: PMC2750862
  • Wei G, Wei L, Zhu J, Zang C, Hu-Li J, Yao Z, Cui K, Kanno Y, Roh T, Watford W, Schones D, Peng W, Sun H, Paul W, O'Shea J, Zhao K. Global mapping of H3K4me3 and H3K27me3 reveals specificity and plasticity in lineage fate determination of differentiating CD4+ T cells. Immunity. 2009;30(1): 155-67. PMID: 19144320 | PMCID: PMC2722509
  • Zang C, Schones D, Zeng C, Cui K, Zhao K, Peng W. A clustering approach for identification of enriched domains from histone modification ChIP-Seq data. Bioinformatics (Oxford, England). 2009;25(15): 1952-8. PMID: 19505939 | PMCID: PMC2732366
  • Wang Z, Zang C, Rosenfeld J, Schones D, Barski A, Cuddapah S, Cui K, Roh T, Peng W, Zhang M, Zhao K. Combinatorial patterns of histone acetylations and methylations in the human genome. Nature genetics. 2008;40(7): 897-903. PMID: 18552846 | PMCID: PMC2769248