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== '''Welcome to the Computational Genomics Lab''' ==  
== '''Computational Cancer Epigenomics and Transcriptomics (PI: Wei Li)''' ==  


[http://www.bcm.edu/cancercenter/ Dan L. Duncan Cancer Center], [http://www.bcm.edu/mcb/index.html Department of Molecular and Cellular Biology], [http://www.bcm.edu/ Baylor College of Medicine]
[http://www.bcm.edu/cancercenter/ Dan L. Duncan Cancer Center], [http://www.bcm.edu/mcb/index.html Department of Molecular and Cellular Biology], [http://www.bcm.edu/ Baylor College of Medicine]
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==Recent News==
==Recent News==
. '''11/2010, New Paper'''
. 03/2015:  Kaifu's MeCP2 mCH binding paper (w/ Zoghbi lab) is accepted to '''PNAS'''.
 
A paper titled "MM-ChIP enables integrative analysis of cross-platform and between-laboratory ChIP-chip/seq data" has been accepted by '''Genome Biology'''.
 
. '''10/2010, New Grant'''


A Texas CPRIT grant has been funded. We will work with Dr. Goodell at BCM to understand the Role of DNA Methylgransferase 3B in normal and malignant hematopoiesis.  
. 01/2015:  Deqiang, HJ and Ben's HSC novel noncoding RNA paper is accepted to '''Cell Stem Cell''' -- the 100th paper we published.


. '''09/2010, New Paper'''
. 01/2015:  Zheng's collaborative work on PRMT9 is accepted to '''Nature Communications'''.


A paper titled "A High Resolution Map of the Drosophila Transcriptome by Paired-End RNA-Sequencing" has been accepted by '''Genome Research'''.
. 12/2014:  Zheng Xia is awarded a '''Keck fellowship''' in Computational Cancer Biology.


. '''08/2010, New Grant'''
. 11/2014:  Zheng's DaPars 3'UTR Pan Cancer analysis paper is published in '''Nature Communications'''.


Our Pilot Project has been funded by BCM Stem Cells and Regenerative Medicine Center (STaR).  
. 09/2014:  Liguo's ChIP-exo methodology paper (MACE) is accepted to '''Nucleic Acids Research'''.  MACE is recommended by Active Motif as the software solution for the company's new [https://www.activemotif.com/catalog/1050/chip-exo ChIP-exo kit and service].


. '''07/2010, New Paper'''
. 09/2014: Deqiang will start his tenure-track assistant professor position. Job well done. 


The Epigenome Consortium paper titled "Sequencing-Based Sequence-based profiling of DNA methylation: comparisons of methods and catalogue of allelic epigenetic modifications" has been accepted by '''Nature Biotechnology'''.
. 09/2014:  Zheng's prostate cancer RNA-seq paper with Dr. Balk at Harvard is accepted to '''Molecular Cancer Research '''.  


. '''06/2010, New Postdoc'''
. 09/2014:  Yuanxin's work on H3K79 Methylation with Dr. Shi is accepted to '''Cell'''.


Hao Zhao will join us as a postdoc fellow. Hao has a PhD in Computer Science from City University of Hong Kong. Welcome!
. 08/2014:  '''Three Collaborative CPRIT grants''' are funded: DNA methylation with Goodell lab, 3'UTR with Wagner lab and ZM11 with Shi lab.


. '''05/2010, New Paper'''
. 08/2014:  Kaifu's "super promoter" paper is under review in '''Nature Genetics'''.


Our paper titled "Histone modifications and chromatin organization in prostate cancer" has been accepted by '''Epigenomics'''.
. 06/2014:  Deqiang's Dnmt3a/3b double KO paper (w/ Goodell Lab) is accepted to '''Cell Stem Cell '''.  


. '''01/2010, New Grant'''
. 06/2014:  Zheng's alternative splicing paper (w/ Cooper Lab) is accepted to '''Molecular Cell '''.


A Texas CPRIT grant has been funded. We will use ChIP-seq and RNA-seq to analyze Androgen Receptor (AR) function in Prostate Cancer with Dr. Weigel at BCM.
. 02/2014:  Zheng's collaborative work on alternative splicing in heart development is accepted to '''Nature Communications'''.  


. '''01/2010, New Grant'''
. 02/2014:  Zheng's brain tumor 3'UTR regulator paper is accepted to '''Nature'''. This paper was initially rejected after review twice. We appealed twice with success and finally made it in the 3rd submission.


A planning award for the Lonestar Oncology Network for EpigeneticS Therapy And Research (LONESTAR) was funded. This project will bring together a "dream team" in epigenetics research from UT Southwestern, Baylor College of Medicine, and M.D. Anderson.  We will direct the bioinformatics component for LONESTAR.
. 02/2014:  Welcome our new postdoc Jianzhong Su and graduate student Xueqiu Lin.


. '''01/2010, [http://www.aacr.org/home/scientists/meetings--workshops/special-conferences/cancer-epigenetics.aspx Conference on Cancer Epigenetics]'''
. 02/2014:  Deqiang's mouse HSC Aging Epigenomics paper is accepted in principle to '''Cell Stem Cell'''.


Wei Li is an invited speaker in the American Association for Cancer Research (AACR) Special Conference on Cancer Epigenetics at Puerto Rico.
. 01/2014:  Deqiang's Methodology paper for the detection of differential DNA Methylation (MOABS) is accepted to '''Genome Biology'''.


. '''12/24/2009, New Paper'''
. 01/2014:  Our collaborative work on Breast Cancer Epigenetics is accepted to '''Science Translational Medicine'''.


Dr.Bert O'Malley's paper, Global Characterization of Transcriptional Impact of the SRC-3 Coregulator, has been accepted by '''Molecular Endocrinology'''. Liguo and Wei are co-authors on the paper.
. 01/2014:  Yuanxin and Zheng's ZM11 paper with Xiaobing Shi lab in MD Anderson is accepted to '''Nature'''. This work links transcription elongation to tumor suppression.


. '''12/08/2009, New Paper'''
. 12/2013: Kaifu's aging nucleosome paper is accepted to ''' Genes & Development'''  


Liguo's paper titled 'A Statistical Method for the Detection of Alternative Splicing Using RNA-seq' has been accepted by '''PLoS ONE'''. Congratulations Liguo!
. 12/2013: We received a 5-year NIH/NHGRI '''R01''' grant (scored at 6 percentile in its first submission) to study DNA Methylation


. '''11/13/2009, New Grant'''
. 11/2013: Wei will serve on the Editorial Board of '''Molecular Endocrinology'''


Wei Li received a '''New Investigator Award''' from the Department of Defense (DOD) Prostate Cancer Research Program (PCRP). Cheers!
. 09/2013:  Deqiang's DNA methylation Canyon paper is accepted to '''Nature Genetics'''.


. '''11/07/2009, Keynote Presentation'''
. 09/2013:  Xueqiu's bisulfite sequencing quality control paper (BSeQC) is accepted to '''Bioinformatics'''.


Wei Li gave a Keynote Presentation at the Symposium on Advances in Cell Signaling, Cancer Prevention and Therapy at South Padre Island, Texas.
. 08/2013:  Kadir's p53 paper is accepted to '''Nucleic Acids Research'''


. '''09/29/2009, New Grant'''
. 01/2013:  [http://www.bcm.edu/news/item.cfm?newsID=6723 BCM News] and [http://epigenie.com/danpos-reveals-dynamic-nucleosomes Epigenie Headline] about our recent work on nucleosome dynamics.
 
A prestigious NIH Challenge grant was funded. We will use ChIP-seq to analyze RXRa binding in mouse liver with Dr. Karpen at Texas Children's Hospital.
 
. '''09/17/2009, New Grant'''
 
A two-year $2.5 million NIH Grand Opportunity (GO) grant was funded. We will study aging epigenomics with Drs. Darlington and Goodell at BCM.
 
. '''09/15/2009, New Grant'''
 
A prestigious NIH Challenge grant was funded. We will use RNA-seq to characterize patient cardiac progenitors with Dr. Pu at Harvard Medical School.
 
. '''06/05/2009, New BMC Bioinformatics Paper'''
 
Yuanxin's paper titled 'BSMAP: whole genome Bisulfite Sequence MAPping program' has been accepted by '''BMC Bioinformatics'''. Congratulations Yuanxin!
 
. '''03/26/2009, New Cell Paper'''
 
A paper titled 'Reprogrammed Androgen Receptor Function in Androgen-Independent Prostate Cancer' has finally been accepted by '''Cell'''.




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[http://openwetware.org/wiki/Li_Lab:news News Archive]
[http://openwetware.org/wiki/Li_Lab:news News Archive]
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== '''A Genomic View of Epigenetic and Transcriptional Regulation''' ==
Our lab is focused on the design and application of bioinformatics algorithms to elucidate global epigenetic mechanisms and transcription dynamics in normal development and diseases such as cancer. Since establishing the lab in early 2008, we have published more than 70 peer-reviewed papers through solid methodology development and extensive collaboration research, including 26 in Nature, Science and Cell series.
 
We have developed a number of widely used algorithms to analyze next generation sequencing data from ChIP-seq (MACS, MACE), DNA methylation Bisulfite-seq (BSMAP/RRBSMAP, BSeQC, MOABS), nucleosome positioning MNase-seq (DANPOS), and RNA-seq (CPAT, RSeQC, DaPars). These algorithms have been broadly adopted by thousands of academic users. For example, the MACS algorithm has gathered >1900 citations since 2008.


In collaboration with experimental biologists, we used these algorithms to gain novel biological insights from various biological processes and disease models.


Our lab is focused on the design and application of statistical and computational algorithms to elucidate global epigenetic and transcriptional regulatory mechanism, by interpreting and integrating data from ChIP-chip/seq, DNA methylation, Nucleosome positioning, Alternative splicing and Motif finding.
* '''Chromatin Factors''': ER in breast cancer, AR in prostate cancer, FoxA1 pioneer factor, Atoh1 in neuron development, NSD2 in oncogenic programming, SIRT7 in cancer transformation, ZM11 in transcription elongation, and p53 in ES differentiation..


An elaborate system of epigenetic and transcription regulation is responsible for the morphological and behavioral complexity in higher eukaryotes. This regulatory system consists of diverse trans-acting protein factors, cis-acting regulatory DNA sequences and the underlying epigenomic background, such as histone modifications, DNA methylation and Nucleosome localizations. Recently, Chromatin ImmunoPrecipitation coupled with whole genome tiled microarray (ChIP-chip) and/or next-generation sequencing (Solexa, SOLiD and 454) has evolved as a powerful and unbiased technique to study this genome-wide regulatory system. The application of this technology to multiple factors and/or in multiple conditions allows biologists to study how transcription is differentially regulated in a combinatorial manner. However, it also poses great challenges for the development of effective algorithms, the key link between massive raw data and biological hypotheses.
* '''DNA Methylation''': DNA methylation Canyon, Epigenetic changes in HSC aging, Dnmt3a in HSC differentiation and cancer transformation.  


We developed a series of algorithms to reliably detect and annotate ChIP-enriched regions using Next-generation sequencing (MACS; Genome Biology 2008) and Affymetrix whole-genome tiling arrays, including 1) Model-based Analysis of Tiling-arrays (MAT; PNAS 2006) and a hidden Markov model (Bioinformatics 2005) for ChIP-region detection, 2) extreme MApping of OligoNucleotide (xMAN; BMC Genomics 2008) for microarray probe mapping, 3) Cis-regulatory Element Annotation System (CEAS; NAR 2006) for ChIP-region annotation. Since the inception in early 2006, they have been adopted by hundreds of academic users and are now considered as the ChIP-chip data analysis standard in many labs.  We worked with ENCODE consortium to systematically analyze the performance variability introduced in ChIP-chip protocols, array platforms, and analysis methods (Genome Res. 2008). Furthermore, we are also in close collaboration with several labs on identifying global regulation targets of several key transcription factors, including Estrogen Receptor (Cell 2005; Nature Genetics 2006); Androgen Receptor (Molecular Cell 2007; Cell 2009) and FoxA1 (Cell 2008).
* '''Nucleosome Organization''': Fragile nucleosome in stress-response, Promoter nucleosome with Tup1, Nucleosome dynamics in ES differentiation, and Global nucleosome loss in yeast aging.


We are currently collaborating with many BCM laboratories to use the Next generation sequencing to study 1) Transcription factor binding and histone modifications (ChIP-seq); 2) DNA methylation at single nucleotide resolution (Bisulfite-seq); 3) Nucleosome remodeling (Mnase-seq); 4) Alternative splicing (RNA-seq).  My laboratory also plays an important role in the BCM Epigenomics Data Analysis and Coordination Center for a five-year [http://nihroadmap.nih.gov/epigenomics/referenceepigenomeconsortium.asp NIH Roadmap Epigenomics Program].  
* '''Transcriptome''': chimeric RNA in prostate cancer, Long non-coding RNA in HSC, 3’UTR deletion in cancer and its master regulator CFIm25. .


[http://sites.google.com/a/bcm.edu/lilab/ Lab Intranet]
[http://sites.google.com/a/bcm.edu/lilab/ Lab Intranet]
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Revision as of 14:09, 27 March 2015

Home        People        Publications        Collaborations        Software        Positions        Contact       


Recent News

. 03/2015: Kaifu's MeCP2 mCH binding paper (w/ Zoghbi lab) is accepted to PNAS.

. 01/2015: Deqiang, HJ and Ben's HSC novel noncoding RNA paper is accepted to Cell Stem Cell -- the 100th paper we published.

. 01/2015: Zheng's collaborative work on PRMT9 is accepted to Nature Communications.

. 12/2014: Zheng Xia is awarded a Keck fellowship in Computational Cancer Biology.

. 11/2014: Zheng's DaPars 3'UTR Pan Cancer analysis paper is published in Nature Communications.

. 09/2014: Liguo's ChIP-exo methodology paper (MACE) is accepted to Nucleic Acids Research. MACE is recommended by Active Motif as the software solution for the company's new ChIP-exo kit and service.

. 09/2014: Deqiang will start his tenure-track assistant professor position. Job well done.

. 09/2014: Zheng's prostate cancer RNA-seq paper with Dr. Balk at Harvard is accepted to Molecular Cancer Research .

. 09/2014: Yuanxin's work on H3K79 Methylation with Dr. Shi is accepted to Cell.

. 08/2014: Three Collaborative CPRIT grants are funded: DNA methylation with Goodell lab, 3'UTR with Wagner lab and ZM11 with Shi lab.

. 08/2014: Kaifu's "super promoter" paper is under review in Nature Genetics.

. 06/2014: Deqiang's Dnmt3a/3b double KO paper (w/ Goodell Lab) is accepted to Cell Stem Cell .

. 06/2014: Zheng's alternative splicing paper (w/ Cooper Lab) is accepted to Molecular Cell .

. 02/2014: Zheng's collaborative work on alternative splicing in heart development is accepted to Nature Communications.

. 02/2014: Zheng's brain tumor 3'UTR regulator paper is accepted to Nature. This paper was initially rejected after review twice. We appealed twice with success and finally made it in the 3rd submission.

. 02/2014: Welcome our new postdoc Jianzhong Su and graduate student Xueqiu Lin.

. 02/2014: Deqiang's mouse HSC Aging Epigenomics paper is accepted in principle to Cell Stem Cell.

. 01/2014: Deqiang's Methodology paper for the detection of differential DNA Methylation (MOABS) is accepted to Genome Biology.

. 01/2014: Our collaborative work on Breast Cancer Epigenetics is accepted to Science Translational Medicine.

. 01/2014: Yuanxin and Zheng's ZM11 paper with Xiaobing Shi lab in MD Anderson is accepted to Nature. This work links transcription elongation to tumor suppression.

. 12/2013: Kaifu's aging nucleosome paper is accepted to Genes & Development

. 12/2013: We received a 5-year NIH/NHGRI R01 grant (scored at 6 percentile in its first submission) to study DNA Methylation

. 11/2013: Wei will serve on the Editorial Board of Molecular Endocrinology

. 09/2013: Deqiang's DNA methylation Canyon paper is accepted to Nature Genetics.

. 09/2013: Xueqiu's bisulfite sequencing quality control paper (BSeQC) is accepted to Bioinformatics.

. 08/2013: Kadir's p53 paper is accepted to Nucleic Acids Research

. 01/2013: BCM News and Epigenie Headline about our recent work on nucleosome dynamics.


News Archive




Our lab is focused on the design and application of bioinformatics algorithms to elucidate global epigenetic mechanisms and transcription dynamics in normal development and diseases such as cancer. Since establishing the lab in early 2008, we have published more than 70 peer-reviewed papers through solid methodology development and extensive collaboration research, including 26 in Nature, Science and Cell series.

We have developed a number of widely used algorithms to analyze next generation sequencing data from ChIP-seq (MACS, MACE), DNA methylation Bisulfite-seq (BSMAP/RRBSMAP, BSeQC, MOABS), nucleosome positioning MNase-seq (DANPOS), and RNA-seq (CPAT, RSeQC, DaPars). These algorithms have been broadly adopted by thousands of academic users. For example, the MACS algorithm has gathered >1900 citations since 2008.

In collaboration with experimental biologists, we used these algorithms to gain novel biological insights from various biological processes and disease models.

  • Chromatin Factors: ER in breast cancer, AR in prostate cancer, FoxA1 pioneer factor, Atoh1 in neuron development, NSD2 in oncogenic programming, SIRT7 in cancer transformation, ZM11 in transcription elongation, and p53 in ES differentiation..
  • DNA Methylation: DNA methylation Canyon, Epigenetic changes in HSC aging, Dnmt3a in HSC differentiation and cancer transformation.
  • Nucleosome Organization: Fragile nucleosome in stress-response, Promoter nucleosome with Tup1, Nucleosome dynamics in ES differentiation, and Global nucleosome loss in yeast aging.
  • Transcriptome: chimeric RNA in prostate cancer, Long non-coding RNA in HSC, 3’UTR deletion in cancer and its master regulator CFIm25. .


Lab Intranet openwetware


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