Guocheng Yuan

Department of Biostatistics and Computational Biology, Dana-Farber Cancer Institute

We develop statistical and computational methodologies for genomic data analysis and integration, with the aim to understand systems-level gene regulatory mechanisms. More specifically, our research has been focused on epigenomics. A multi-cellular organism contains only one genome, but different cell types contain different epigenomic patterns: chromatin structure, histone modification, and DNA methylations. These epigenomic marks are important for regulating protein-DNA binding activities and gene transcription. We have developed algorithms to analyze tiling array data, thereby probing genome-scale chromatin structure at high resolutions. We also integrate epigenomic information with other data such as genotypic information and RNA expression in order to estimate the direct regulatory effects of epigenetic factors. We are currently investigating the role of epigenetic effects in cancer cells.

Another area of interest is to build predictive models for important biological pathways. We study how cell behavior is changed under perturbation of regulatory networks, with particular interest in studying how phenotypic diversity can arise in genomically identical cell populations.

Ph.D., 1999, University of Maryland at College Park

Yuan GC. Linking genome to epigenome. WIREs Systems Biology and Medicine. (invited review)

Larson JL, Yuan GC. Chromatin states accurately classify cell differentiation stages. PLoS ONE. accepted.

Pinello L, Lo Bosco G, Hanlon B, Yuan GC. A model-free method for estimating sequence specificity. BMC Bioinformatics. 2011 Oct 21:12(1):408.

Van Rechem C, Black JC, Abbas TA, Allen A, Rinehart CA, Yuan GC, Dutta A, Whetstine JR.  The SKP1 - Cul1 - F-box and Leucine-rich repeat protein 4 (SCF-FbxL4) ubiquitin ligase regulates lysine demethylase 4A (KDM4A)/Jumonji domain-containing 2A (JMJD2A). Journal of Biological Chemistry. 2011 Sep 2;286(35):30462-70.

Larson JL, Yuan GC. Epigenetic domains found in mouse embryonic stem cells via a hidden Markov model. BMC Bioinformatics. 2010 Nov 12;11(1):557.

Rao S, Shao Z, Roumiantsev S, McDonald LT, Yuan GC, Orkin SH. Differential Roles of Sall4 Isoforms in Embryonic Stem Cell Pluripotency. Mol Cell Biol. 2010 Nov;30(22):5364-80

Fang R, Barbera AJ, Xu Y, Rutenberg M, Leonor T, Bi Q, Lan F, Mei P, Yuan GC, Lian C, Peng J, Cheng D, Sui G, Kaiser UB, Shi Y, Shi YG. Human LSD2/KDM1b/AOF1 regulates gene transcription by modulating intragenic H3K4me2 methylation. Molecular Cell 2010. Jul 30;39(2):222-33.

Chastanet A, Vitkup D, Yuan GC, Norman TM, Liu JS, Losick R. Broadly heterogeneous activation of the master regulator for sporulation in Bacillus subtilis.  Proceedings of the National Academy of Sciences 2010 May 4;107(18):8486-91.

Liu Y*, Shao Z*, Yuan GC. Prediction of Polycomb target plasticity in mouse embryonic stem cells.  Genomics 2010. July;96: 17-26. (cover article; * joint first-authors.)

Lantermann AB, Straub T, Strålfors A, Yuan GC, Eckwall K, Korber P. Schizosaccharomyces pombe genome-wide nucleosome mapping reveals positioning mechanisms distinct from Saccharomyces cerevisiae. Nature Structural and Molecular Biology 2010 Feb;17(2):251-7.

Shen X, Kim W, Fujiwara Y, Liu Y, Mysliwiec MR, Yuan GC, Lee Y, Orkin SH. Jumonji modulates Polycomb activity and self-renewal versus differentiation of stem cells. Cell 2009 Dec 24;139(7):1303-14.

Wippo CJ, Krstulovic BS, Ertel F, Musladin S, Blaschke D, Stürzl S, Yuan GC, Hörz W, Korber P, Barbaric S. Differential cofactor requirements for histone eviction from two nucleosomes at the yeast PHO84 promoter are determined by intrinsic nucleosome stability. Molecular and Cellular Biology 2009 June;29(11): 2960-81.

Di Gesù V, Lo Bosco G, Pinello L, Yuan GC, Corona DFV.  A multi-layer method to study genome-scale positions of nucleosomes, Genomics. 2009 Feb;93(2):140-5

Yuan GC. Targeted recruitment of histone modifications in humans predicted by genomic sequences.  Journal of Computational Biology 2009 Feb;16(2): 341-355. (accepted paper for RECOMB Regulatory Genomics).

Shen X, Liu Y, Hsu YJ, Fujiwara Y, Kim J, Mao X, Yuan GC, Orkin SH, EZH1 mediates methylation on histone H3 lysine 27 and complements EZH2 in maintaining stem cell identity and executing pluripotency. Molecular Cell 2008. Nov 21;32(4):491-502.

Yuan, G.C. and J.S. Liu, Genomic sequence is highly predictive of local nucleosome depletion. PLoS Computational Biology 2008 Jan;4(1):e13.

Dennis JH, Fan HY, Reynolds SM, Yuan G, Meldrim JC, Richter DJ, Peterson DG, Rando OJ, Noble WS, Kingston RE. Independent and complementary methods for large-scale structural analysis of mammalian chromatin. Genome Research 2007 Jun;17(6):928-39.

Yuan, G.C.*, P. Ma*, W. Zhong, and J.S. Liu, Statistical Assessment of the Global Regulatory Role of Histone Acetylation in Saccharomyces cerevisiae, Genome Biology, 2006, 7, p. R70. (* equal first author).

Yuan, G.C., Y.-J. Liu, M.F. Dion, M.D. Slack, L.F. Wu, S.J. Altschuler, and O.J. Rando, Genome-scale Identification of Nucleosome Positions in S. Cerevisiae, Science, 2005, 309(5734), p.626