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== '''Computational Cancer Epigenomics and Transcriptomics (PI: Wei Li)''' ==  
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== '''A Genomic View of Epigenetic and Transcriptional Regulation''' ==
[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]


</div>


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.
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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.
 
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).
 
We are currently collaborating with many BCM laboratories to use the Next generation sequencing to study 1) Transcription factor binding (ChIP-seq); 2) DNA methylation at single nucleotide resolution (BS-seq); 3) Nucleosome positioning (Nu-seq); 4) Cancer specific alternative splicing junctions (RNA-seq).  My laboratory also plays an important role in the BCM Epigenomics Data Analysis and Coordination Center for a five-year $190 million [http://nihroadmap.nih.gov/epigenomics/fundedresearch.asp NIH Roadmap Epigenomics Program].
 
[http://sites.google.com/a/bcm.edu/lilab/ Lab Intranet]
 
[[Image:WeiLi.jpg‎]]
 
</div>


==Recent News==
==Recent News==
. '''06/05/2009, New BMC Bioinformatics Paper'''
. 08/2015: Kaifu's Cancer Big-data analysis paper is published in '''Nature Genetics'''. This work links broad H3K4me3 to pan-cancer tumor suppressors. See Nature Editor’s [http://blogs.nature.com/freeassociation/2015/08/methylation-marks-tumor-suppressors.html Blog] and Chinese Report in [http://www.ebiotrade.com/newsf/2015-8/2015825165005119.htm ebiotrade.com]


Yuanxin's paper titled 'BSMAP: whole genome Bisulfite Sequence MAPping program' has been accepted by '''BMC Bioinformatics'''. Congratulations Yuanxin!
. 07/2015: Wei will become a regular member of the '''NIH GCAT''' (Genomics, Computational Biology and Technology) study section.


. 06/2015: Kaifu will start his '''tenure-track faculty''' position at Cornell University & Methodist Hospital. Congratulations!


. '''06/04/2009, New Postdoc (joint with Prof. Xuewen Pan)'''
. 06/2015: We will receive a '''NEW NIH/NCI R01''' grant (scored at 5%ile) to study 3`UTR alternations in human cancers. 


Kaifu Chen has accepted our postdoc offer. Kaifu has a PhD in Genomics and Bioinformatics from Beijing Institute of Genomics, Chinese Academy of Sciences. Welcome Kaifu!
. 03/2015:  Kaifu's MeCP2 mCH binding paper (w/ Zoghbi lab) is accepted to '''PNAS'''.


. 3/2015: We received a NEW '''CPRIT''' grant. 


. '''04/30/2009, New Postdoc (joint with Prof. Huda Zoghbi)'''
. 01/2015:  Deqiang, HJ and Ben's HSC novel noncoding RNA paper is accepted to '''Cell Stem Cell''' -- the 100th paper we published.


Peng Yu has accepted our postdoc offer. Peng will soon finish his PhD in computer engineering at the University of Texas at Austin, and join our lab this summer. Welcome Peng!
. 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'''.


. '''03/26/2009, New Cell Paper'''
. 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].


A paper titled 'Reprogrammed Androgen Receptor Function in Androgen-Independent Prostate Cancer' has finally been accepted by '''Cell'''.
. 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 '''.


. '''03/20/2009, [http://cancerepigenome.pbwiki.com/ Cancer Epigenomics Workshop]'''
. 09/2014:  Yuanxin's work on H3K79 Methylation with Dr. Shi is accepted to '''Cell'''.


Please join us on May 2nd (Saturday) 2009 at MD Anderson Cancer Center. This meeting is organized by Steffi Oesterreich, Wei Li and Jean-Pierre Issa.
. 08/2014:  '''Three Collaborative CPRIT grants''' are funded: DNA methylation with Goodell lab, 3'UTR with Wagner lab and ZM11 with Shi lab.


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


. '''03/18/2009, New Student'''
. 06/2014:  Zheng's alternative splicing paper (w/ Cooper Lab) is accepted to '''Molecular Cell '''.


Julia Kristine Blackmore, a PhD student in BCM MCB dept., will be doing a two-month rotation in our lab.  
. 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.


. '''03/16/2009, New Course'''
. 02/2014:  Deqiang's mouse HSC Aging Epigenomics paper is accepted in principle to '''Cell Stem Cell'''.


[http://sites.google.com/site/mcbseminar/ 320-466 MCB Seminar]
. 01/2014: Deqiang's Methodology paper for the detection of differential DNA Methylation (MOABS) is accepted to '''Genome Biology'''.


. 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.




. '''01/21/2009, New Paper'''


A paper titled 'Integrative analysis of HIF binding and transactivation reveals its role in maintaining histone methylation homeostasis' has been accepted by '''PNAS'''.
[[Image:Banner.jpg‎‎]]


[http://openwetware.org/wiki/Li_Lab:news News Archive]


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===Header===


</div>
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 75 peer-reviewed papers through solid methodology development and extensive collaboration research, including 28 in '''Nature, Science and Cell''' series.


* '''Been well-funded''' by NIH and Texas CPRIT with total external funding >$1.3 million per year. Dr Li is the PI on the following 4 major grants: NIH R01HG007538 (2013-2018) and R01CA193466 (2015-); CPRIT RP110471-C3 (2011-2016) and RP150292 (2015-2018).
* '''Mentored''' the first 3 postdoc trainees to start their tenure track faculty positions in prestigious research institutions in the US.


<div style="border-bottom: 1px dashed #9999CC;">
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.
===Header===
</div>


|}
In collaboration with experimental biologists, we used these algorithms to gain novel biological insights from various biological processes and disease models.
</center>
__NOTOC__


== '''A Genomic View of Epigenetic and Transcriptional Regulation''' ==
* '''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.


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.
* '''Nucleosome Organization''': Fragile nucleosome in stress-response, Promoter nucleosome with Tup1, Nucleosome dynamics in ES differentiation, and Global nucleosome loss in yeast aging.


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.
* '''Transcriptome''': chimeric RNA in prostate cancer, Long non-coding RNA in HSC, 3’UTR deletion in cancer and its master regulator CFIm25. .


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).
[http://sites.google.com/a/bcm.edu/lilab/ Lab Intranet]
[http://openwetware.org/wiki/Li_Lab openwetware]
</div>


We are currently collaborating with many BCM laboratories to use the Next generation sequencing to study 1) Transcription factor binding (ChIP-seq); 2) DNA methylation at single nucleotide resolution (BS-seq); 3) Nucleosome positioning (Nu-seq); 4) Cancer specific alternative splicing junctions (RNA-seq).  My laboratory also plays an important role in the BCM Epigenomics Data Analysis and Coordination Center for a five-year $190 million [http://nihroadmap.nih.gov/epigenomics/fundedresearch.asp NIH Roadmap Epigenomics Program].
[http://sites.google.com/a/bcm.edu/lilab/ Lab Intranet]


<div style="border-bottom: 1px dashed #9999CC;">
[[Image:WeiLi.jpg‎]]
[[Image:WeiLi.jpg‎]]
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__NOTOC__
<div style="clear: right; text-align: left; float: left; padding: .1em 1.5em .9em; ">
 
==Recent News==
. '''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!
 
 
. '''06/04/2009, New Postdoc (joint with Prof. Xuewen Pan)'''
 
Kaifu Chen has accepted our postdoc offer. Kaifu has a PhD in Genomics and Bioinformatics from Beijing Institute of Genomics, Chinese Academy of Sciences.  Welcome Kaifu!
 
 
. '''04/30/2009, New Postdoc (joint with Prof. Huda Zoghbi)'''
 
Peng Yu has accepted our postdoc offer. Peng will soon finish his PhD in computer engineering at the University of Texas at Austin, and join our lab this summer. Welcome Peng!
 
 
. '''03/26/2009, New Cell Paper'''
 
A paper titled 'Reprogrammed Androgen Receptor Function in Androgen-Independent Prostate Cancer' has finally been accepted by '''Cell'''.
 
 
. '''03/20/2009, [http://cancerepigenome.pbwiki.com/ Cancer Epigenomics Workshop]'''
 
Please join us on May 2nd (Saturday) 2009 at MD Anderson Cancer Center. This meeting is organized by Steffi Oesterreich, Wei Li and Jean-Pierre Issa.
 
 
. '''03/18/2009, New Student'''
 
Julia Kristine Blackmore, a PhD student in BCM MCB dept.,  will be doing a two-month rotation in our lab.
 
 
. '''03/16/2009, New Course'''
 
[http://sites.google.com/site/mcbseminar/ 320-466 MCB Seminar]
 
 
 
. '''01/21/2009, New Paper'''
 
A paper titled 'Integrative analysis of HIF binding and transactivation reveals its role in maintaining histone methylation homeostasis' has been accepted by '''PNAS'''.
 
 
 
 
 
 
 
 
 
</div>
</div>

Revision as of 08:23, 26 August 2015

Home        People        Publications        Collaborations        Software        Positions        Contact       


Recent News

. 08/2015: Kaifu's Cancer Big-data analysis paper is published in Nature Genetics. This work links broad H3K4me3 to pan-cancer tumor suppressors. See Nature Editor’s Blog and Chinese Report in ebiotrade.com

. 07/2015: Wei will become a regular member of the NIH GCAT (Genomics, Computational Biology and Technology) study section.

. 06/2015: Kaifu will start his tenure-track faculty position at Cornell University & Methodist Hospital. Congratulations!

. 06/2015: We will receive a NEW NIH/NCI R01 grant (scored at 5%ile) to study 3`UTR alternations in human cancers.

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

. 3/2015: We received a NEW CPRIT grant.

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

. 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.

. 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 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: 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.


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 75 peer-reviewed papers through solid methodology development and extensive collaboration research, including 28 in Nature, Science and Cell series.
  • Been well-funded by NIH and Texas CPRIT with total external funding >$1.3 million per year. Dr Li is the PI on the following 4 major grants: NIH R01HG007538 (2013-2018) and R01CA193466 (2015-); CPRIT RP110471-C3 (2011-2016) and RP150292 (2015-2018).
  • Mentored the first 3 postdoc trainees to start their tenure track faculty positions in prestigious research institutions in the US.

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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