BBS Faculty Member - X. Shirley Liu

X. Shirley Liu

Department of Biostatistics and Computational Biology

Dana-Farber Cancer Institute
Center for Life Science Bldg 11007
450 Brookline Ave.
Boston, MA 02215
Tel: 617-632-2472
Fax: 617-632-2444
Visit my lab page here.

Our research focuses on algorithm development and integrative mining from high throughput data to understand gene regulation in cancer biology. We developed a number of widely used algorithms for transcription factor motif finding, ChIP-chip / ChIP-seq / DNase-seq / CRISPR screen data analysis. Through integrating genome-wide transcription factor binding, chromatin dynamics, gene expression profiles, and chemical and functional screens, we try to model the specificity and function of transcription factors, chromatin regulators, RNA binding proteins, kinases, and lncRNAs in tumor development, progression, drug response and resistance.

Cancer Epigenetics: We have been developing algorithms (MACS, Cistrome, NPS, BETA) to facilitate the analysis of epigenomic data and use integrative modeling approaches to study genomic transcriptional and epigenetic gene regulatory mechanisms underlying tumorigenesis and progression. We are developing new methods to utilize the abundant public ChIP-seq data to infer functional enhancers that regulate the expression, and understand the targets and specificity of epigenetic drugs in cancers.

CRISPR screens: We are developing the computational methods for the design (SSC), analysis (MAGeCK), hit prioritization (NEST), and visualization (VISPR) of genome-wide CRISPR screens. We are also using this technology to identify key genes in breast and prostate tumor progression and drug resistance. We also develop CRISPR screen platforms to understand the functions of enhancers and long-noncoding RNAs, and identify synthetic lethal gene pairs in cancer that leads to optimized cancer precision medicine.

Cancer immunology: We are developing novel computational algorithms to systematically deconvolve the abundance of different immune cell types. Applying the deconvolution method on over 10K tumor samples from TCGA identified widespread clinical associations with tumor infiltrating immune cells. Our investigations on cancer vaccine and checkpoint blockade targets suggest that systematic analyses of tumor immunity have the potential to inform effective cancer immunotherapies.

Last Update: 8/19/2015


Liu XS@, Brutlag DL, Liu JS (2002). An algorithm for finding protein-DNA binding sites with applications to chromatin immunoprecipitation microarray experiments. Nat Biotechnol. 20(8):835-9.

Johnson WE#, Li W#, Meyer CA#, Gottardo R, Carroll JS, Brown M,
Liu XS (2006). MAT: Model-based Analysis of Tiling-arrays for ChIP-chip. Proc Natl Acad Sci U S A. 103(33): 12457-12462. PMCID:PMC1567901

Carroll JS, Meyer CA, Song J, Li W, Brodsky AS, Hall G, Geistlinger TR, Eeckhoute J, Wang QB, Bekiranov S, Sementchenko V, Fox EA, Silver PA, Gingeras TR,
Liu XS*, Brown M* (2006). Genome wide analysis of estrogen receptor binding sites. Nat Genet. 38:1289-97.

Zhang Y#, Liu T#, Meyer CA, Eeckhoute J, Johnson DS, Bernstein B, Nusbaum C, Myers RM, Brown M, Li W,
Liu XS (2008). Model-based analysis of ChIP-Seq (MACS). Genome Biol. 9(9):R137. PMCID:PMC2592715.

Wang Q#, Li W#, Zhang Y, Yuan X, Beroukhim R, Wang H, Lupien M, Wu T, Regan MM, Meyer CA, Carroll JS, Manrai AK, Jänne OA, Balk SP, Mehra R, Chinnaiyan AM, Rubin MA, True L, Giorentino M, Fiore C, Loda M, Kantoff PW,
Liu XS*, Brown M* (2009). Androgen receptor regulates a distinct transcription program in androgen-independent prostate cancer. Cell. 138(2):245-56. PMCID:PMC2726827.

He HH#, Meyer C#, Shin H, Bailey ST, Wei G, Wang Q, Zhang Y, Xu K, Ni M, Lupien M, Mieczkowski P, Lieb JD, Zhao K, Brown M*,
Liu XS* (2010). Nucleosome dynamics defines transcriptional enhancers. Nat Genet, 42(4):343-7. PMCID:PMC2932437.

Liu T#, Rechtsteiner A#, Egelhofer TA#, Vielle A#, et al, Ahringer J*, Strome S*,
Liu XS* (2011). Broad chromosomal domains of histone modification patterns in C. elegans. Genome Res. 21(2):227-36. PMCID:PMC3032926.

Xu K#, Wu ZJ#, Anna C. Groner AC, He HH, Cai C, Lis RT, Wu X, Stack EC, Loda M, Liu T, Xu H, Cato L, Thornton JE, Gregory RI, Morrissey M, Vessella RL, Montironi R, Magi-Galluzzi C, Kantoff PW, Balk SP,
Liu XS*, Brown M* (2012). EZH2 Oncogenic activity in castration resistant prostate cancer is polycomb-independent. Science. 338(6113):1465-9. PMCID:PMC3625962.

Du Z#, Fei T#, Verhaak RGW, Su Z, Zhang Y, Brown M*, Chen C*,
Liu XS* (2013). Integrative genomic analyses reveal clinically relevant long noncoding RNAs in human cancer. Nat Struct Mol Biol. 20:908-13. PMCID:PMC3702647.

He HH#, Meyer CA#, Hu SS#, Chen MW, Zang C, Liu Y, Rao PK, Fei T, Xu H, Long H*,
Liu XS*, Brown M* (2014). Refined DNase-seq protocol and data analysis reveals intrinsic bias in transcription factor footprint identification. Nat Methods 11(1):73-8. PMCID: PMC4018771.

Li W#, Xu H#, Xiao T, Cong L, Love MI, Zhang F, Irizarry RA, Liu JS, Brown M,
Liu XS (2014). MAGeCK enables robust identification of essential genes from genome-scale CRISPR/Cas9 knockout screens. Genome Biol 15(12):554. PMCID:PMC4290824

Jiang P, Freedman ML, Liu JS,
Liu XS (2015). Inference of transcriptional regulation in cancers. Proc Natl Acad Sci U S A 112(25):7731-6. PMCID: PMC4485084.

© 2015 by the President and Fellows of Harvard College