Xiaole Shirley Liu, PhD
Assistant Professor
Department of Biostatistical Science
Harvard School of Public Health
Dana Farber Cancer Institute
Liu Lab web site
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Xiaole Shirley Liu, PhD Assistant Professor
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Contact: 
Department of Biostatistics and Computational Biology Tel: (617) 632-2472 Dana-Farber Cancer Institute, Harvard School of Public Health Fax: (617) 632-2444 375 Longwood Ave, LW641, Boston MA 02115 Email: xsliu@jimmy.harvard.edu http://genome.dfci.harvard.edu/xsliu/
Teaching:
BIO280: Introduction to Computational Molecular Biology, Spring 2006.
This site received one of three Awards for Achievement in Instructional Technology from the Presidential Instructional Technology Fellows Program at Harvard University.
Research:
Our laboratory focuses on the design of statistical and computational algorithms to discover and explore the genomic sequence elements related to gene regulations. We are especially interested in Chromatin ImmunoPrecipitation coupled with DNA microarray analysis (ChIP-chip) to study the effect of transcription factor binding on transcription regulation.
ChIP-chip studies the in vivo transcription factor binding locations in the genome. Recent commercial high density oligonucleotide arrays that tile all the non-repetitive human genomic sequences allow biologists to conduct unbiased genome-wide ChIP-chip experiments. However, they also generate massive amounts of data (e.g. ChIP-chip on Affymetrix human tiled arrays generates 1.5 GB of data per sample). We design algorithms to identify genomic regions bound by the transcription factor in ChIP-chip on Affymetrix tiled arrays. Our method relies on estimating the array probe behavior by considering probe sequence and copy number in the genome. This method can detect transcription factor binding from a single ChIP-chip experiment without using mismatch probes, control experiments or replicated samples. This is a huge time and money saver for labs testing their ChIP-chip antibodies and protocols, and finding failed replicates contaminating their data.
Once the transcription factor binding locations are determined, we develop a publicly available web server that allows biologists to download genomic sequences, mask sequence repeats, generate sequence conservation plots, map nearby genes, and look for enriched sequence motifs that are bound by the transcription factor and its cooperative binding partners. In the past few years, our laboratory has excelled in computational sequence motif finding and has developed a number of widely-used motif-finding algorithms for different biological applications. For the current study, we integrate ChIP-chip, gene expression microarray, and sequence motif finding to predict the genes regulated by the transcription factor. Our final and most challenging goal in this study is to generalize the global combinatorial regulatory mechanisms of the transcription factor. We are currently collaborating with nine Harvard laboratories to use ChIP-chip to study the regulation of key cancer transcription factors.
In addition, we are interested in bacteria operon prediction, alternative splicing, mRNA stability and translation rate regulation.
Algorithm Software:
BioProspector, MDscan, Motif Regressor, CompareProspector, HMMTiling, MAT, and CEAS.
Selected Publications: Quick Link
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. In press, Nat Gen. *Co-corresponding authors.
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: 12457-12462.
Ji X, Li W, Song J, Wei L, Liu XS (2006). CEAS: Cis-Elements Annotation Systems. Nucleic Acids Res. 34:W551-554.
Zhang Y, Liu XS, Liu Q and Wei L (2006). Genome-wide in silico Identification and Analysis of cis Natural Antisense Transcripts (cis-NATs) in Ten Species. Nucleic Acids Res. 34:3465-3475.
Swinburn IA, Meyer CA, Liu XS, Silver PA, Brodsky AS (2006). Genomic localization of RNA-binding proteins reveals links between pre-mRNA processing and transcription. Genome Res.. 16:912-921
Carroll JS, Liu XS, Brodsky AS, Li W, Szary AJ, Meyer CA, Shao W, Hestermann EV, Geistlinger TR, Fox EA, Silver PA, Brown M (2005). Chromosome-wide mapping of estrogen receptor binding reveals long-range regulation requiring the forkhead protein FoxA1. Cell. 122(1):33-43
Ben-Yehuda S, Jujita M, Liu XS, Gorbatyuk B, Skoko D, Yan J, Eichenberger P, Rudner DZ, Marko JF, Liu JS, Losick R (2005). Defining a centromere-like element in Bacillus subtilis by identifying the binding sites for the chromosome-anchoring protein RacA. Mol Cell. 17(6):773-82.
Li W, Meyer CA, Liu XS (2005). A hidden Markov model for analyzing ChIP-chip experiments on genome tiling arrays and its application to p53 binding sequences. Bioinformatics (ISMB2005). 21 Suppl 1:i274-i282.
Yildiz FH, Liu XS, Heydorn A, Schoolnik GK (2004). Molecular Analysis of Rugosity in a Vibrio cholerae O1 El Tor phase variant. Mol Microbiol. 53(2):497-515.
Liu Y, Wei L, Batzoglou S, Brutlag DL, Liu JS, Liu XS (2004). A suite of web-based programs to search for transcriptional regulatory motifs. Nucleic Acids Res. 32:W204-W207.
Liu Y*, Liu XS*, Wei L, Altman RB, Batzoglou (2004). Conservation of eukaryotic regulatory elements and their identification using comparative genomics. Genome Res. 14:451-8. *Joint first authors.
Conlon EM*, Liu XS*, Lieb JD, Liu JS (2003). Integrating regulatory motif discovery and genome-wide expression analysis. Proc Natl Acad Sci U S A. 100:3339-44. *Joint first authors.
Liu XS*, Brutlag DL, Liu JS (2002). An algorithm for finding protein-DNA binding sites with applications to chromatin immunoprecipitation microarray experiments. Nat Biotechnol. 20:835-9. *Xiaole Liu added middle name Shirley.
Lieb JD, Liu X, Botstein D, Brown PO (2001). Promoter-specific binding of Rap1 revealed by genome-wide maps of protein-DNA association. Nat Gen. 28:327-34.
Liu X, Brutlag DL, Liu JS (2001). BioProspector: discovering conserved DNA motifs in upstream regulatory regions of co-expressed genes. Proc Pac Symp Biocomput. 127-38.