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We are working on RNA at the interface of Systems Biology, Computer Science and Molecular Neuroscience, currently sponsored by NIH, Simons Foundation, and Columbia University Medical Center.
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__NOTOC__
  
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=Organizational principles and functional impact of neuronal RNA-regulatory networks=
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[[Publications|Papers]] | [[Talks]]
  
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The importance of post-transcriptional regulation at the RNA level for orchestrated gene expression in mammalian systems is increasingly recognized.  Such regulation is dictated by interaction of at least several hundred RNA-binding proteins (RBPs) with their target transcripts, or RNA-regulatory networks, and has profound impact on the output of the transcriptome, especial for the development and function of the nervous system. 
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['''*''' co-first authors; '''†''' co-corresponding authors]
  
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To understand the function of RNA regulatory network, a first step is to infer the structure of such networks, which is challenging due in part to the fact that most RBPs recognize very short and generate sequence motifs with limited information content.  In the past few years, we took advantage of advances in high-throughput biochemical and molecular biology assays (most of which are related to next-generation sequencing), such as HITS-CLIP (or CLIP-Seq) and RNA-Seq that profile transcriptomes and protein-RNA interactomes.  We applied these assays to specific neuronal RBPs,mostly using mouse brain as a model system, and intersect them with statistical and machine learning approaches to identify exons under tissue-specific regulation and predict specific protein-RNA interactions at single nucleotide resolution.  Importantly, we also developed an integrative modeling approach to combine multiple modalities of data to infer direct and functional targets of specific RBPs with high accuracy and sensitivity. Investigation of the resulting networks allow us to make unexpected findings such as combinatorial regulation by multiple RBPs.
 
  
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For our current work, one focus is to investigate systematically how multiple RBPs work together to derive dynamic regulation during neurodevelopment. We aim to find predictive rules of combinatorial regulation, and how groups of RBPs define subsets of target transcripts that are functional distinct.  To this end, we rely on the structure of RBPs defined by integrative modeling approaches, and statistical inference to determine the correlation structure underlying time series transcriptome data.
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==2015==
  
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Another exciting direction is the use of embryonic stem cells (ESCs) and in vitro differentiation of neurons from (ESCs).  We collaborate with Hynek Wichterle group at Columbia, who developed and optimized the directed, in vitro differentiation of motor neurons, a group of nerve cells through which the brain controls muscle contraction. Motor neurons are also the primary targets in several devastating neuron degenerative diseases including amyotrophic lateral sclerosis (ALS) and spinal muscular satrapy (SMA).  This system has two key advantages: 1) the differential process recapitulate many key aspects of in vivo motor neuron development; 2) the use of ES cells makes it possible to leverage genome engineering techniques to perturb RNA regulatory networks.  By dissecting RNA regulatory networks in detail, we hope to obtain a deeper understanding of their functional impact and the underlying regulatory mechanisms in this well defined, clinically relevant cell type.
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=====MBNL sequestration by toxic RNAs and RNA misprocessing in the myotonic dystrophy brain=====
  
 +
Goodwin, M., Mohan, A. Batra, R., Lee, K.-Y., Charizanis, K., Francisco Jose Fernandez-Gomez, F.J., Eddarkaoui, S., Sergeant, N., Buee, L., Kimura, T., Clark, H.B., Dalton, J., Takamura, K., <b>Weyn-Vanhentenryck, S.M. </b>, <b>Zhang, C.</b>, Reid, T., Ranum, L.P.W., Day, J.W., Swanson, M.S. 2015.
  
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*Zhang, C.†, Frias, M.A., Mele, A., Ruggiu, M., Eom, T., Marney, C.B., Wang, H., Licatalosi, D.D., Fak, J.J., Darnell, R.B.† 2010. Integrative modeling defines the Nova splicing-regulatory network and its combinatorial controls. ''Science'', 329: 439-443.
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''Cell Rep.'' http://dx.doi.org/10.1016/j.celrep.2015.07.029.
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*Zhang, C.*, Zhang, Z.*, Castle, J., Sun, S., Johnson, J., Krainer, A.R. and Zhang, M.Q. 2008. Defining the regulatory network of the tissue-specific splicing factors Fox-1 and Fox-2. ''Genes Dev'', 22:2550-2563.
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=Variation of RNA-regulatory networks in evolution, human populations and in neuronal disorders=
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[http://www.ncbi.nlm.nih.gov/pubmed/26257173 PubMed]
 +
[http://www.cell.com/cell-reports/pdf/S2211-1247(15)00789-5.pdf PDF]
  
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A second related direction of our lab is to evaluate the impact of mutations on RNA regulation in normal physiology or disease. Our study spans three contexts: comparison of different species (e.g. rodents and primates), different human populations, and patients affected by neurological diseases and normal controls. Such study is facilitated by our ability to determine protein-RNA interactions at a high resolution and distinction of functional vs. nonfunctional interactions.  We will apply this strategy to parallel systems in different species that directly comparable, large transcriptome profiles of human populations generated by consortium efforts, and mutations identified by genomic sequencing compiled from the public domain and collaborators.  
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=====mRIN for direct assessment of genome-wide and gene-specific mRNA integrity from large-scale RNA sequencing data=====
 +
<b>Feng, H.</b>, Zhang, X., <b>Zhang, C.† </b>, 2015.  
  
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*Weyn-Vanhentenryck,S.,M.*, Mele,A.*, Yan,Q.*, Sun,S., Farny,N., Zhang,Z., Xue,C., Herre,M., Silver,P.A., Zhang,M.Q., Krainer,A.R., Darnell,R.B. Zhang,C. † 2014.  HITS-CLIP and integrative modeling define the Rbfox splicing-regulatory network linked to brain development and autism. ''Cell Rep'' In press.
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''Nat Comm.'' '''6''':7816. doi: 10.1038/ncomms8816.
  
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=High-throughput transcriptomic data analysis=
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[http://www.ncbi.nlm.nih.gov/pubmed/26234653 PubMed]
 +
[http://www.pnas.org/content/early/2015/03/02/1502849112.full.pdf PDF]
 +
[http://zhanglab.c2b2.columbia.edu/index.php/mRIN Software]
  
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Our work heavily relies on high-throughput technologies which produce enormous amount of data, and algorithms to transform these data into useful information.  We are interested in developing better algorithms to process transcroptomic data, such as mapping RNA-Seq reads, discovering and quantifying RNA processing in specific conditions, and analyzing CLIP data to map protein-RNA interactions at a single nucleotide resolution.
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- Research highlights, “How good are those RNA-seq data?”, ''Nature Methods'', <b>12</b>:910 (2015).
  
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*Moore, M.*, Zhang, C.*, Gantman, E.C., Mele, A., Darnell, J.C., Darnell, R.B. 2014. Mapping Argonaute and conventional RNA-binding protein interactions with RNA at single-nucleotide resolution using HITS-CLIP and CIMS analysis. Nat Protocols.  9:263-293. ([[CIMS_Documentation|Software]])
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=====Systematic discovery of regulated and conserved alternative exons in the mammalian brain reveals NMD modulating chromatin regulators.=====
  
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*Wu,J., Anczukow,O., Krainer,A.R., Zhang,M.Q. †, Zhang,C. †, 2013. OLego: Fast and sensitive mapping of spliced mRNA-Seq reads using small seeds. ''Nucleic Acids Res.'' , In press. ([[OLego|Software]])
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<b>Yan, Q.*</b>, <b>Weyn-Vanhentenryck, S.M.*</b>,<b>Wu, J.</b>, Sloan, S.A., Zhang, Y., Chen, K., Wu, J.-Q., Barres, B.A.†, <b>Zhang, C.†</b>, 2015.
  
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*Zhang, C.†, Darnell, R.B.† 2011. Mapping in vivo protein-RNA interactions at single-nucleotide resolution from HITS-CLIP data. ''Nat Biotech'', 29:607-614.
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''Proc. Nat. Acad. Sci. USA.'' Mar 3. pii: 201502849.
 +
 
 +
[http://www.ncbi.nlm.nih.gov/pubmed/25737549 PubMed]
 +
[http://www.nature.com/ncomms/2015/150803/ncomms8816/pdf/ncomms8816.pdf PDF]
 +
[http://zhanglab.c2b2.columbia.edu/index.php/Cortex_AS Supp Info]
 +
 
 +
==2014==
 +
 
 +
=====Loss of MBNL function leads to disruption of developmentally regulated alternative polyadenylation in RNA-mediated disease=====
 +
 
 +
Batra, R., Charizanis, K., Manchanda, M., Mohan, A., Li, M., Finn, D.J., Goodwin, <b>Zhang, C.</b>, Sobczak,K., Thornton, C.A., Swanson, M.S. 2014.
 +
 
 +
''Mol Cell.'' 56: 311-322.
 +
 
 +
[http://www.ncbi.nlm.nih.gov/pubmed/25263597 PubMed]
 +
[http://www.sciencedirect.com/science/article/pii/S1097276514006820/pdfft?md5=c81d51c9f97e8d76d1e21a5c75941edd&pid=1-s2.0-S1097276514006820-main.pdf PDF]
 +
 
 +
=====An RNA-Sequencing transcriptome and splicing database of glia, neurons, and vascular cells of the cerebral cortex=====
 +
 
 +
Zhang, Y., Chen, K., Sloan, S., Bennett, M.L., Scholze, A.R., O’Keeffe, S., Phatnani, H.P., Guarnieri, P., Caneda, C., Ruderisch, N., Deng, S., Liddelow, S.A., <b>Zhang, C.</b>, Daneman, R., Maniatis, T., Barres, B.A., Wu, J.-Q. 2014. 
 +
 
 +
''J Neurosci.'' 34:11929-11947.
 +
 
 +
[http://www.ncbi.nlm.nih.gov/pubmed/25186741 PubMed]
 +
[http://www.jneurosci.org/content/34/36/11929.full.pdf+html PDF]
 +
 
 +
=====HITS-CLIP and integrative modeling define the Rbfox splicing-regulatory network linked to brain development and autism=====
 +
 
 +
<b>Weyn-Vanhentenryck, S.M.</b>*, Mele,A.*, <b>Yan,Q.</b>*, Sun,S., Farny,N., Zhang,Z., Xue,C., Herre,M., Silver,P.A., Zhang,M.Q., Krainer,A.R., Darnell,R.B. †, <b>Zhang,C.</b> † 2014. 
 +
 
 +
''Cell Rep.'' 10.1016/j.celrep.2014.02.005.
 +
 
 +
[http://www.ncbi.nlm.nih.gov/pubmed/24613350 PubMed]
 +
[http://download.cell.com/cell-reports/pdf/PIIS2211124714000849.pdf PDF]
 +
[http://zhanglab.c2b2.columbia.edu/index.php/CIMS software]
 +
 
 +
=====Mapping Argonaute and conventional RNA-binding protein interactions with RNA at single-nucleotide resolution using HITS-CLIP and CIMS analysis=====
 +
 
 +
Moore, M.*, <b>Zhang, C.</b>*, Gantman, E.C., Mele, A., Darnell, J.C., Darnell, R.B. 2014.
 +
 
 +
''Nat Protocols'', 9:263-293.
 +
 
 +
[http://www.ncbi.nlm.nih.gov/pubmed/24407355?dopt=Abstract PubMed]
 +
[http://www.nature.com/nprot/journal/v9/n2/pdf/nprot.2014.012.pdf PDF]
 +
[http://zhanglab.c2b2.columbia.edu/index.php/CIMS software]
 +
 
 +
==2013==
 +
 
 +
=====Progressive impairment of muscle regeneration in Muscleblind-like 3 isoform knockout mice=====
 +
 
 +
Poulos, M.G., Batra, R., Li, M., Yuan, Y., <b>Zhang, C.</b>, Darnell, R.B., Swanson, M.S. 2013.
 +
 
 +
''Hum Mol Genet.'' 22:3547-3558.
 +
 
 +
[http://www.ncbi.nlm.nih.gov/pubmed/23660517?dopt=Abstract PubMed]
 +
[http://hmg.oxfordjournals.org/content/early/2013/05/08/hmg.ddt209.full.pdf+html PDF]
 +
 
 +
=====Prediction of clustered RNA-binding protein motif sites in the mammalian genome=====
 +
 
 +
<b>Zhang, C.</b> †, Lee, K.-Y., Swanson, M.S., Darnell, R.B. † 2013.
 +
 
 +
''Nucleic Acids Res.'' 41:6793-6807.
 +
[http://nar.oxfordjournals.org/content/early/2013/05/17/nar.gkt421.full.pdf PDF]
 +
[http://zhanglab.c2b2.columbia.edu/index.php/MCarts_Documentation software]
 +
 
 +
=====OLego: Fast and sensitive mapping of spliced mRNA-Seq reads using small seeds=====
 +
 
 +
<b>Wu,J.</b>, Anczukow,O., Krainer,A.R., Zhang,M.Q. †, <b>Zhang,C.</b> †, 2013.
 +
 +
''Nucleic Acids Res.'' 41:5149-5163.
 +
 
 +
[http://www.ncbi.nlm.nih.gov/pubmed/23571760?dopt=Abstract PubMed]
 +
[http://nar.oxfordjournals.org/content/early/2013/04/08/nar.gkt216.full.pdf+html PDF]
 +
[http://zhanglab.c2b2.columbia.edu/index.php/OLego software]
 +
 
 +
 
 +
 
 +
 
 +
[Publications before my own lab]
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 +
==2012==
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 +
 
 +
 
 +
=====NOVA-dependent regulation of cryptic NMD exons controls synaptic protein levels after seizure=====
 +
 
 +
Eom,T., <b>Zhang,C.</b>, Wang,H., Lay,K., Fak,J., Noebels,J.L., Darnell,R.B. 2012.
 +
 
 +
''eLife'', 2:e00178.
 +
 
 +
[http://www.ncbi.nlm.nih.gov/pubmed/23359859‎?dopt=Abstract PubMed]
 +
[http://elife.elifesciences.org/content/elife/2/e00178.full.pdf PDF]
 +
 
 +
=====Neuronal Elav-like (Hu) Proteins Regulate RNA Splicing and Abundance to Control Glutamate Levels and Neuronal Excitability=====
 +
 
 +
Ince-Dunn, G., Okano, H.J., Jensen, K.B., Park, W.Y., Zhong, R., Ule, J., Mele,A., Fak, J.J., Yang, C., <b>Zhang,C.</b>, Yoo, J., Herre, M., Okano, H., Noebels, J.L., Darnell, R.B., 2012. 
 +
 
 +
''Neuron'', 75:1067-1080.
 +
 
 +
[http://www.ncbi.nlm.nih.gov/pubmed/22998874?dopt=Abstract PubMed]
 +
[http://ac.els-cdn.com/S0896627312006587/1-s2.0-S0896627312006587-main.pdf?_tid=4b5c6686-28eb-11e2-af58-00000aacb35f&acdnat=1352300362_a80f3a1435a1357a9a6b45a3918673c5 PDF]
 +
 
 +
=====The lncRNA Malat1 is dispensable for mouse development but its transcription plays a cis-regulatory role in the adult=====
 +
 
 +
Zhang,B.,  Arun,G., Mao,Y.S., Lazar,Z., Hung,G., Bhattacharjee,G., Xiao,X., Booth,C.J., Wu,J., <b>Zhang,C.</b>, Spector,D.L., 2012. 
 +
 
 +
''Cell Reports'', 2:111-123.
 +
 
 +
[http://pdn.sciencedirect.com/science?_ob=MiamiImageURL&_cid=280959&_user=276325&_pii=S2211124712001635&_check=y&_origin=article&_zone=toolbar&_coverDate=26-Jul-2012&view=c&originContentFamily=serial&wchp=dGLbVlS-zSkWb&md5=8fe31b35ab69517df50fb38ff54ee1ad&pid=1-s2.0-S2211124712001635-main.pdf&sqtrkid=0.7794181457720697 PubMed]
 +
[http://genesdev.cshlp.org/content/26/14/1626.full.pdf PDF]
 +
 
 +
=====Muscleblind-like 2 mediated alternative splicing in the developing brain and dysregulation in myotonic dystrophy=====
 +
 
 +
Charizanis, K., Lee, K.-Y., Batra, R., Goodwin, M., <b>Zhang,C.</b>, Yuan, Y., Shuie, L., Cline, M., Scotti, M.M., Xia, G., Kumar,A., Ashizawa, T., Clark, H.B., Kimura, T., Takahashi, M.P., Fujimura, H., Jinnai, K., Yoshikawa, H., Pereira,M.G., Gourdon,G., Sakai,N., Nishino,S., Foster,T.C., Ares, M. Jr, Darnell, R.B. Swanson, M.S., 2012. 
 +
 
 +
''Neuron'', 75:437-450.
 +
 
 +
[http://www.ncbi.nlm.nih.gov/pubmed/22884328?dopt=Abstract PubMed]
 +
[http://pdn.sciencedirect.com/science?_ob=MiamiImageURL&_cid=272195&_user=276325&_pii=S0896627312005259&_check=y&_origin=article&_zone=toolbar&_coverDate=09-Aug-2012&view=c&originContentFamily=serial&wchp=dGLzVBA-zSkWb&md5=5e68e7ef32a60388a706be10de84c960&pid=1-s2.0-S0896627312005259-main.pdf&sqtrkid=0.5248918924480677&sqtrkid=0.14140767510980368&sqtrkid=0.7367502509150654&sqtrkid=0.6107530847657472&sqtrkid=0.8712234853301197&sqtrkid=0.9306223317980766&sqtrkid=0.6240476940292865&sqtrkid=0.5726298945955932&sqtrkid=0.4283553180284798&sqtrkid=0.6780585322994739&sqtrkid=0.9059713387396187&sqtrkid=0.30562901636585593 PDF]
 +
 
 +
=====Ptbp2 represses adult-specific splicing to regulate the generation of neuronal precursors in the embryonic brain=====
 +
 
 +
Licatalosi,D.D., Yano,M., Fak,J.J., Mele,A., Grabinski,S.E., <b>Zhang,C.</b>, Darnell,R.B., 2012. 
 +
 
 +
''Genes Dev'', 26:1626-1642.
 +
 
 +
[http://www.ncbi.nlm.nih.gov/pubmed/22802532?dopt=Abstract PubMed]
 +
[http://genesdev.cshlp.org/content/26/14/1626.full.pdf PDF]
 +
 
 +
==2011==
 +
 
 +
=====Identification of novel androgen-regulated pathways and mRNA isoforms through genome-wide exon-specific profiling of the LNCaP transcriptome=====
 +
 
 +
Rajan P., Dalgliesh, C., Carling, P., Buist, T., <b>Zhang,C.</b>, Grellscheid, S., Armstrong, K., Stockley, J., Simillion, C., Gaughan, L., Kalna, G., Zhang, M.Q., Robson, C., Leung, H., Elliott, D. 2011. 
 +
 
 +
''PLoS One'', 6: e29088.
 +
 
 +
[http://www.ncbi.nlm.nih.gov/pubmed/22194994?dopt=Abstract PubMed]
 +
[http://www.plosone.org/article/fetchObjectAttachment.action?uri=info%3Adoi%2F10.1371%2Fjournal.pone.0029088&representation=PDF PDF]
 +
 
 +
=====Study of FoxA pioneer factor at silent genes reveals Rfx-repressed enhancer at Cdx2 and a potential indicator of esophageal adenocarcinoma development=====
 +
 
 +
Watts, J.A., <b>Zhang,C.</b>, Klein-Szanto, A.J., Kormish, J.D., Fu, J., Zhang, M.Q., Zaret, K.S. 2011.
 +
 
 +
''PLoS Genet'', 7: e1002277.
 +
 
 +
[http://www.ncbi.nlm.nih.gov/pubmed/21935353?dopt=Abstract PubMed]
 +
[http://www.plosgenetics.org/article/fetchObjectAttachment.action?uri=info%3Adoi%2F10.1371%2Fjournal.pgen.1002277&representation=PDF PDF]
 +
 
 +
=====FMRP stalls ribosomal translocation on mRNAs linked to synaptic function and autism=====
 +
 
 +
Darnell, J.C., Van Driesche, S.J., <b>Zhang,C.</b>, Hung, K.Y.S., Mele, A., Fraser, C.E., Stone, E.F., Chen, C., Fak, J.J., Chi, S.W., Licatalosi, D.D., Richter, J.D., Darnell, R.B., 2011.
 +
 
 +
''Cell'', 146:247-261.
 +
 
 +
[http://www.ncbi.nlm.nih.gov/pubmed/21784246?dopt=Abstract PubMed]
 +
[http://download.cell.com/pdf/PIIS0092867411006556.pdf PDF]
 +
 
 +
=====Mapping in vivo protein-RNA interactions at single-nucleotide resolution from HITS-CLIP data=====
 +
 
 +
<b>Zhang,C.</b>†, Darnell, R.B.† 2011.  
 +
 
 +
''Nat. Biotech.'' 29:607-614.
 +
 
 +
[http://www.ncbi.nlm.nih.gov/pubmed/21633356?dopt=Abstract PubMed]
 +
[http://www.nature.com/nbt/journal/v29/n7/pdf/nbt.1873.pdf PDF]
 +
[http://zhanglab.c2b2.columbia.edu/index.php/CIMS software]
 +
 
 +
==2010==
 +
 
 +
=====Integrative modeling defines the Nova splicing-regulatory network and its combinatorial controls=====
 +
 
 +
<b>Zhang,C.</b>†, Frias, M.A., Mele, A., Ruggiu, M., Eom, T., Marney, C.B., Wang, H.,  Licatalosi, D.D., Fak, J.J., Darnell, R.B.† 2010.
 +
 
 +
''Science''. 329: 439-443.
 +
[http://www.ncbi.nlm.nih.gov/pubmed/20558669?dopt=Abstract PubMed]
 +
[http://www.sciencemag.org/cgi/rapidpdf/science.1191150v1.pdf PDF]
 +
 
 +
- Editor’s choice, Pickersgill, H. 2010. Making the Final Cut. <i>Sci. Signal.</i> 3:ec234; <br>
 +
 
 +
- Nominated by leading researchers as one of the 33 papers that represent breakthroughs in computational biology in 2010. Mak H.C., 2011. Trends in computational biology-2010. <i>Nat Biotech.</i> 29, doi:10.1038/nbt.1747.
 +
 
 +
=====Dissecting the unique role of the retinoblastoma tumor suppressor during cellular senescence=====
 +
 
 +
Chicas, A., Wang, X., <b>Zhang,C.</b>, McCurrach, M., Zhao Z., Ozlem, M., Dickins, R., Narita, M., Zhang, M.Q., and Lowe, S.W. 2010.
 +
 
 +
''Cancer Cell''. 17:376-387.
 +
 
 +
[http://www.ncbi.nlm.nih.gov/pubmed/20385362?dopt=Abstract PubMed]
 +
[http://www.sciencedirect.com/science/article/pii/S1535610810000723/pdfft?md5=a191ed96242c05f575dfa856697ecbab&pid=1-s2.0-S1535610810000723-main.pd  PDF]
 +
 
 +
- Comment in <i>Cancer Cell.</i> 2010 Apr 13;17(4):313-4.
 +
 
 +
==2008 or earlier==
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 +
=====Expression of 24,426 human alternative splicing events and predicted cis regulation in 48 tissues and cell lines=====
 +
 
 +
Castle, J.C., <b>Zhang,C.</b>, Shah, J.K., Kulkarni, A.V., Cooper, T.A., Johnson, J.M. 2008.
 +
 
 +
''Nature Genet.'' 40:1416-1425.
 +
 
 +
[http://www.ncbi.nlm.nih.gov/pubmed/18978788?dopt=Abstract PubMed]
 +
[http://www.nature.com/ng/journal/v40/n12/pdf/ng.264.pdf PDF]
 +
 
 +
=====Defining the regulatory network of the tissue-specific splicing factors Fox-1 and Fox-2=====
 +
 
 +
<b>Zhang,C.</b>*, Zhang, Z.*, Castle, J., Sun, S., Johnson, J., Krainer, A.R. and Zhang, M.Q. 2008.
 +
 +
''Genes Dev''. 22:2550-2563.
 +
 
 +
[http://www.ncbi.nlm.nih.gov/pubmed/18794351?dopt=Abstract PubMed]
 +
[http://genesdev.cshlp.org/cgi/reprint/22/18/2550 PDF]
 +
 
 +
=====An RNA landscape of evolution for optimal exon and intron discrimination=====
 +
 
 +
<b>Zhang,C.</b>, Li, W.-H., Krainer, A.R. and Zhang, M.Q. 2008.
 +
 
 +
''Proc. Nat. Acad. Sci. USA''. 105:5797-802.
 +
 
 +
[http://www.ncbi.nlm.nih.gov/pubmed/18391195?dopt=Abstract PubMed]
 +
[http://www.pnas.org/content/105/15/5797.full.pdf+html PDF]
 +
 
 +
=====Dual-specificity splice sites function alternatively as 5&#39; and 3&#39; splice sites=====
 +
 
 +
<b>Zhang,C.</b>, Hasting, M.L., Krainer, A.R., Zhang, M.Q. 2007.
 +
 +
''Proc. Nat. Acad. Sci. USA.'' 104(38): 15028-15033
 +
 +
[http://www.ncbi.nlm.nih.gov/pubmed/17848517?dopt=Abstract PubMed]
 +
[http://www.pnas.org/cgi/content/full/104/38/15028 PDF].
 +
 
 +
=====Evolutionary impact of limited splicing fidelity in mammalian genes=====
 +
 
 +
<b>Zhang,C.</b>, Krainer A.R., Zhang, M.Q. 2007.
 +
 
 +
''Trends Genet.'' 23(10): 484-488.
 +
 
 +
[http://www.ncbi.nlm.nih.gov/pubmed/17719121?dopt=Abstract PubMed]
 +
[http://www.sciencedirect.com/science?_ob=ArticleURL&amp;_udi=B6TCY-4PGXF12-1&_user=429752&amp;_coverDate=08/24/2007&amp;_rdoc=1&amp;_fmt=&amp;_orig=search&amp;_sort=d&amp;view=c&amp;_acct=C000020578&amp;_version=1&amp;_urlVersion=0&amp;_userid=429752&amp;md5=18d53f024a0cc53702a98f6b14a7b154 PDF]
 +
 
 +
=====An increased specificity score matrix for the prediction of SF2/ASF-specific exonic splicing enhancers=====
 +
 
 +
Smith, P.J., <b>Zhang,C.</b>, Wang, J., Chew, S.L., Zhang, M.Q., Krainer, A.R. 2006.
 +
 
 +
''Hum Mol Genet'', 15:16):2490-2508.
 +
 
 +
[http://www.ncbi.nlm.nih.gov/pubmed/16825284?dopt=Abstract PubMed]
 +
[http://hmg.oxfordjournals.org/cgi/reprint/ddl171v1 PDF]
 +
 
 +
=====Profiling alternatively spliced mRNA isoforms for prostate cancer classification=====
 +
 
 +
<b>Zhang,C.</b>, Li, H.-R., Fan, J.-B., Wang-Rodriguez, J., Downs, T., Fu, X.-D. and Zhang, M.Q. 2006.
 +
 
 +
''BMC Bioinformatics'', 7:202.
 +
 
 +
[http://www.ncbi.nlm.nih.gov/pubmed/16608523?dopt=Abstract PubMed]
 +
[http://www.biomedcentral.com/content/pdf/1471-2105-7-202.pdf PDF]
 +
 
 +
=====Neighbor Number, Valley Seeking and Clustering=====
 +
 
 +
Zhang,C.</b>, Zhang, X., Zhang, M.Q. and Li, Y. 2007.
 +
 
 +
''Pattern Recognition Letters'',28:173-180.
 +
 
 +
=====A Clustering property of highly-degenerate transcription factor binding sites in the mammalian genome=====
 +
 
 +
<b>Zhang,C.</b>, Xuan, Z., Otto, S., Hover, J.R., McCorkle, S.R., Mandel, G. and Zhang, M.Q. 2006.
 +
 
 +
''Nucl Acids Res'', 34: 2238-2246.
 +
 
 +
[http://www.ncbi.nlm.nih.gov/pubmed/16670430?dopt=Abstract PubMed]
 +
[http://nar.oxfordjournals.org/cgi/reprint/34/8/2238 PDF]
 +
 
 +
=====Significance of Gene Ranking for Classification of Microarray Samples=====
 +
 
 +
<b>Zhang,C.</b>*, Lu, X.* and Zhang, X. 2005.
 +
 
 +
''IEEE/ACM Transactions on Computational Biology and Bioinformatics'', 3(3): 312-320.
 +
 
 +
[http://www.ncbi.nlm.nih.gov/pubmed/17048468?dopt=Abstract PubMed]
 +
 
 +
==Book Chapters==
 +
 
 +
=====Identification of Splicing Factor Target Genes by High-Throughput Sequencing=====
 +
 
 +
<b>Zhang,C.</b>, Zhang,M.Q. 2012.
 +
 
 +
Chapter 51 <i>in Alternative pre-mRNA Splicing: Theory and Protocols. </i>(S. Stamm, C.W. J. Smith, R. Lührmann, ed). Wiley-VCH Verlag GmbH & Co.
 +
 
 +
=====Functional <i>in sillico</i> analysis of gene regulatory polymorphism=====
 +
 
 +
<b>Zhang,C.</b>, Zhao,X. and Zhang,M.Q. 2006. <br>
 +
 
 +
Chapter 12. In <i>Bioinformatics for Geneticists: A Bioinformatics primer for the analysis of genetic data</i>.&nbsp; 2nd Ed. (M.R. Barnes, ed.) &nbsp;John Wiley &amp; Sons, LTD.
 +
 
 +
=====Biomedical literature mining=====
 +
 
 +
<b>Zhang,C.</b>, Zhang,M.Q. 2007. <br>
 +
 
 +
Chap 10. in <i>Introduction to Bioinformatics: A workbook approach</i>. (V. Mathura ed) Elsevier.

Latest revision as of 22:00, 10 March 2016


Papers | Talks

[* co-first authors; † co-corresponding authors]


2015

MBNL sequestration by toxic RNAs and RNA misprocessing in the myotonic dystrophy brain

Goodwin, M., Mohan, A. Batra, R., Lee, K.-Y., Charizanis, K., Francisco Jose Fernandez-Gomez, F.J., Eddarkaoui, S., Sergeant, N., Buee, L., Kimura, T., Clark, H.B., Dalton, J., Takamura, K., Weyn-Vanhentenryck, S.M. , Zhang, C., Reid, T., Ranum, L.P.W., Day, J.W., Swanson, M.S. 2015.

Cell Rep. http://dx.doi.org/10.1016/j.celrep.2015.07.029.

PubMed PDF

mRIN for direct assessment of genome-wide and gene-specific mRNA integrity from large-scale RNA sequencing data

Feng, H., Zhang, X., Zhang, C.† , 2015.

Nat Comm. 6:7816. doi: 10.1038/ncomms8816.

PubMed PDF Software

- Research highlights, “How good are those RNA-seq data?”, Nature Methods, 12:910 (2015).

Systematic discovery of regulated and conserved alternative exons in the mammalian brain reveals NMD modulating chromatin regulators.

Yan, Q.*, Weyn-Vanhentenryck, S.M.*,Wu, J., Sloan, S.A., Zhang, Y., Chen, K., Wu, J.-Q., Barres, B.A.†, Zhang, C.†, 2015.

Proc. Nat. Acad. Sci. USA. Mar 3. pii: 201502849.

PubMed PDF Supp Info

2014

Loss of MBNL function leads to disruption of developmentally regulated alternative polyadenylation in RNA-mediated disease

Batra, R., Charizanis, K., Manchanda, M., Mohan, A., Li, M., Finn, D.J., Goodwin, Zhang, C., Sobczak,K., Thornton, C.A., Swanson, M.S. 2014.

Mol Cell. 56: 311-322.

PubMed PDF

An RNA-Sequencing transcriptome and splicing database of glia, neurons, and vascular cells of the cerebral cortex

Zhang, Y., Chen, K., Sloan, S., Bennett, M.L., Scholze, A.R., O’Keeffe, S., Phatnani, H.P., Guarnieri, P., Caneda, C., Ruderisch, N., Deng, S., Liddelow, S.A., Zhang, C., Daneman, R., Maniatis, T., Barres, B.A., Wu, J.-Q. 2014.

J Neurosci. 34:11929-11947.

PubMed PDF

HITS-CLIP and integrative modeling define the Rbfox splicing-regulatory network linked to brain development and autism

Weyn-Vanhentenryck, S.M.*, Mele,A.*, Yan,Q.*, Sun,S., Farny,N., Zhang,Z., Xue,C., Herre,M., Silver,P.A., Zhang,M.Q., Krainer,A.R., Darnell,R.B. †, Zhang,C. † 2014.

Cell Rep. 10.1016/j.celrep.2014.02.005.

PubMed PDF software

Mapping Argonaute and conventional RNA-binding protein interactions with RNA at single-nucleotide resolution using HITS-CLIP and CIMS analysis

Moore, M.*, Zhang, C.*, Gantman, E.C., Mele, A., Darnell, J.C., Darnell, R.B. 2014.

Nat Protocols, 9:263-293.

PubMed PDF software

2013

Progressive impairment of muscle regeneration in Muscleblind-like 3 isoform knockout mice

Poulos, M.G., Batra, R., Li, M., Yuan, Y., Zhang, C., Darnell, R.B., Swanson, M.S. 2013.

Hum Mol Genet. 22:3547-3558.

PubMed PDF

Prediction of clustered RNA-binding protein motif sites in the mammalian genome

Zhang, C. †, Lee, K.-Y., Swanson, M.S., Darnell, R.B. † 2013.

Nucleic Acids Res. 41:6793-6807. PDF software

OLego: Fast and sensitive mapping of spliced mRNA-Seq reads using small seeds

Wu,J., Anczukow,O., Krainer,A.R., Zhang,M.Q. †, Zhang,C. †, 2013.

Nucleic Acids Res. 41:5149-5163.

PubMed PDF software



[Publications before my own lab]

2012

NOVA-dependent regulation of cryptic NMD exons controls synaptic protein levels after seizure

Eom,T., Zhang,C., Wang,H., Lay,K., Fak,J., Noebels,J.L., Darnell,R.B. 2012.

eLife, 2:e00178.

PubMed PDF

Neuronal Elav-like (Hu) Proteins Regulate RNA Splicing and Abundance to Control Glutamate Levels and Neuronal Excitability

Ince-Dunn, G., Okano, H.J., Jensen, K.B., Park, W.Y., Zhong, R., Ule, J., Mele,A., Fak, J.J., Yang, C., Zhang,C., Yoo, J., Herre, M., Okano, H., Noebels, J.L., Darnell, R.B., 2012.

Neuron, 75:1067-1080.

PubMed PDF

The lncRNA Malat1 is dispensable for mouse development but its transcription plays a cis-regulatory role in the adult

Zhang,B., Arun,G., Mao,Y.S., Lazar,Z., Hung,G., Bhattacharjee,G., Xiao,X., Booth,C.J., Wu,J., Zhang,C., Spector,D.L., 2012.

Cell Reports, 2:111-123.

PubMed PDF

Muscleblind-like 2 mediated alternative splicing in the developing brain and dysregulation in myotonic dystrophy

Charizanis, K., Lee, K.-Y., Batra, R., Goodwin, M., Zhang,C., Yuan, Y., Shuie, L., Cline, M., Scotti, M.M., Xia, G., Kumar,A., Ashizawa, T., Clark, H.B., Kimura, T., Takahashi, M.P., Fujimura, H., Jinnai, K., Yoshikawa, H., Pereira,M.G., Gourdon,G., Sakai,N., Nishino,S., Foster,T.C., Ares, M. Jr, Darnell, R.B. Swanson, M.S., 2012.

Neuron, 75:437-450.

PubMed PDF

Ptbp2 represses adult-specific splicing to regulate the generation of neuronal precursors in the embryonic brain

Licatalosi,D.D., Yano,M., Fak,J.J., Mele,A., Grabinski,S.E., Zhang,C., Darnell,R.B., 2012.

Genes Dev, 26:1626-1642.

PubMed PDF

2011

Identification of novel androgen-regulated pathways and mRNA isoforms through genome-wide exon-specific profiling of the LNCaP transcriptome

Rajan P., Dalgliesh, C., Carling, P., Buist, T., Zhang,C., Grellscheid, S., Armstrong, K., Stockley, J., Simillion, C., Gaughan, L., Kalna, G., Zhang, M.Q., Robson, C., Leung, H., Elliott, D. 2011.

PLoS One, 6: e29088.

PubMed PDF

Study of FoxA pioneer factor at silent genes reveals Rfx-repressed enhancer at Cdx2 and a potential indicator of esophageal adenocarcinoma development

Watts, J.A., Zhang,C., Klein-Szanto, A.J., Kormish, J.D., Fu, J., Zhang, M.Q., Zaret, K.S. 2011.

PLoS Genet, 7: e1002277.

PubMed PDF

FMRP stalls ribosomal translocation on mRNAs linked to synaptic function and autism

Darnell, J.C., Van Driesche, S.J., Zhang,C., Hung, K.Y.S., Mele, A., Fraser, C.E., Stone, E.F., Chen, C., Fak, J.J., Chi, S.W., Licatalosi, D.D., Richter, J.D., Darnell, R.B., 2011.

Cell, 146:247-261.

PubMed PDF

Mapping in vivo protein-RNA interactions at single-nucleotide resolution from HITS-CLIP data

Zhang,C.†, Darnell, R.B.† 2011.

Nat. Biotech. 29:607-614.

PubMed PDF software

2010

Integrative modeling defines the Nova splicing-regulatory network and its combinatorial controls

Zhang,C.†, Frias, M.A., Mele, A., Ruggiu, M., Eom, T., Marney, C.B., Wang, H., Licatalosi, D.D., Fak, J.J., Darnell, R.B.† 2010.

Science. 329: 439-443. PubMed PDF

- Editor’s choice, Pickersgill, H. 2010. Making the Final Cut. Sci. Signal. 3:ec234;

- Nominated by leading researchers as one of the 33 papers that represent breakthroughs in computational biology in 2010. Mak H.C., 2011. Trends in computational biology-2010. Nat Biotech. 29, doi:10.1038/nbt.1747.

Dissecting the unique role of the retinoblastoma tumor suppressor during cellular senescence

Chicas, A., Wang, X., Zhang,C., McCurrach, M., Zhao Z., Ozlem, M., Dickins, R., Narita, M., Zhang, M.Q., and Lowe, S.W. 2010.

Cancer Cell. 17:376-387.

PubMed PDF

- Comment in Cancer Cell. 2010 Apr 13;17(4):313-4.

2008 or earlier

Expression of 24,426 human alternative splicing events and predicted cis regulation in 48 tissues and cell lines

Castle, J.C., Zhang,C., Shah, J.K., Kulkarni, A.V., Cooper, T.A., Johnson, J.M. 2008.

Nature Genet. 40:1416-1425.

PubMed PDF

Defining the regulatory network of the tissue-specific splicing factors Fox-1 and Fox-2

Zhang,C.*, Zhang, Z.*, Castle, J., Sun, S., Johnson, J., Krainer, A.R. and Zhang, M.Q. 2008.

Genes Dev. 22:2550-2563.

PubMed PDF

An RNA landscape of evolution for optimal exon and intron discrimination

Zhang,C., Li, W.-H., Krainer, A.R. and Zhang, M.Q. 2008.

Proc. Nat. Acad. Sci. USA. 105:5797-802.

PubMed PDF

Dual-specificity splice sites function alternatively as 5' and 3' splice sites

Zhang,C., Hasting, M.L., Krainer, A.R., Zhang, M.Q. 2007.

Proc. Nat. Acad. Sci. USA. 104(38): 15028-15033

PubMed PDF.

Evolutionary impact of limited splicing fidelity in mammalian genes

Zhang,C., Krainer A.R., Zhang, M.Q. 2007.

Trends Genet. 23(10): 484-488.

PubMed PDF

An increased specificity score matrix for the prediction of SF2/ASF-specific exonic splicing enhancers

Smith, P.J., Zhang,C., Wang, J., Chew, S.L., Zhang, M.Q., Krainer, A.R. 2006.

Hum Mol Genet, 15:16):2490-2508.

PubMed PDF

Profiling alternatively spliced mRNA isoforms for prostate cancer classification

Zhang,C., Li, H.-R., Fan, J.-B., Wang-Rodriguez, J., Downs, T., Fu, X.-D. and Zhang, M.Q. 2006.

BMC Bioinformatics, 7:202.

PubMed PDF

Neighbor Number, Valley Seeking and Clustering

Zhang,C.</b>, Zhang, X., Zhang, M.Q. and Li, Y. 2007.

Pattern Recognition Letters,28:173-180.

A Clustering property of highly-degenerate transcription factor binding sites in the mammalian genome

Zhang,C., Xuan, Z., Otto, S., Hover, J.R., McCorkle, S.R., Mandel, G. and Zhang, M.Q. 2006.

Nucl Acids Res, 34: 2238-2246.

PubMed PDF

Significance of Gene Ranking for Classification of Microarray Samples

Zhang,C.*, Lu, X.* and Zhang, X. 2005.

IEEE/ACM Transactions on Computational Biology and Bioinformatics, 3(3): 312-320.

PubMed

Book Chapters

Identification of Splicing Factor Target Genes by High-Throughput Sequencing

Zhang,C., Zhang,M.Q. 2012.

Chapter 51 in Alternative pre-mRNA Splicing: Theory and Protocols. (S. Stamm, C.W. J. Smith, R. Lührmann, ed). Wiley-VCH Verlag GmbH & Co.

Functional in sillico analysis of gene regulatory polymorphism

Zhang,C., Zhao,X. and Zhang,M.Q. 2006.

Chapter 12. In Bioinformatics for Geneticists: A Bioinformatics primer for the analysis of genetic data.  2nd Ed. (M.R. Barnes, ed.)  John Wiley & Sons, LTD.

Biomedical literature mining

Zhang,C., Zhang,M.Q. 2007.

Chap 10. in Introduction to Bioinformatics: A workbook approach. (V. Mathura ed) Elsevier.

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