Difference between revisions of "Test"

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−	=Introduction=	+	__NOTOC__
−	Crosslinking induced mutation site or CIMS analysis is a computational method for HITS-CLIP data analysis to determine the exact protein-RNA crosslink sites and thereby map protein-RNA interactions at single-nucleotide resolution.  This method is based on the observation that UV cross linked amino-acid-RNA adducts introduce reverse transcription errors in cDNAs at certain frequencies, which are captured by sequencing and comparison of CLIP tags with the reference genome.  More details can be found in the following references:	+	[[Publications|Papers]] | [[Talks]]
−	<pre>	+
−	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.	+
−	Moore, J.*, Zhang, C.*, Grantman 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(2):263-93.  doi:10.1038/nprot.2014.012.	+	['''*''' co-first authors; '''†''' co-corresponding authors]
−	</pre>	+
−	This brief document provides only the most critical information about how to run the program, which complements a more detailed, step-by-step guide described in the second reference above.
−	=Versions=	+	==2015==
−	*v1.0.1 ( 5-22-2013 ), current	+
−	**Minor internal extension	+
−	**Included joinWrapper.py which was missing in the previous version	+
−	*v1.0.0 ( 12-14-2012 )	+
−	**The initial public release	+
−	=Download=	+	=====MBNL sequestration by toxic RNAs and RNA misprocessing in the myotonic dystrophy brain=====
−	'''Source code:'''	+	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.
−	*czplib (perl): a perl library with various functions for genomic/bioinformatic analysis. ([http://sourceforge.net/p/czplib/ download from SourceForge.net])	+	''Cell Rep.'' http://dx.doi.org/10.1016/j.celrep.2015.07.029.
−	*CIMS (perl): the core algorithm. ([http://sourceforge.net/p/ngs-cims/ download from SourceForge.net])	+
−	=Installation=	+	[http://www.ncbi.nlm.nih.gov/pubmed/26257173 PubMed]
		+	[http://www.cell.com/cell-reports/pdf/S2211-1247(15)00789-5.pdf PDF]
−	==Prerequisites==	+	=====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.
−	This software is implemented with perl . It also relies on several standard linux/unix tools such as grep, cat, sort, etc. We have tested the software on RedHat Linux, although it is expected to work on most unix-like systems, including Mac OS X.	+	''Nat Comm.'' '''6''':7816. doi: 10.1038/ncomms8816.
−	==Steps to install the software==	+	[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]
−	* Download the perl library files czplib, if not already.	+	- Research highlights, “How good are those RNA-seq data?”, ''Nature Methods'', <b>12</b>:910 (2015).
−	Decompress it and move it to a place you like	+	=====Systematic discovery of regulated and conserved alternative exons in the mammalian brain reveals NMD modulating chromatin regulators.=====
−	<pre>	+	<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.
−	$tar zxvf czplib.v1.0.x.tgz	+
−	$mv czplib /usr/local/lib	+
−	</pre>	+
−	Add the library path to the environment variable, so perl can find it.	+	''Proc. Nat. Acad. Sci. USA.'' Mar 3. pii: 201502849.
−	<pre>	+
−	PERL5LIB=/usr/local/lib/czplib	+
−	</pre>	+
−	* Download CIMS codes, if not already.	+	[http://www.ncbi.nlm.nih.gov/pubmed/25737549 PubMed]
−	Decompress it and move it to a place you like	+	[http://www.nature.com/ncomms/2015/150803/ncomms8816/pdf/ncomms8816.pdf PDF]
		+	[http://zhanglab.c2b2.columbia.edu/index.php/Cortex_AS Supp Info]
−	<pre>	+	==2014==
−	$tar zxvf CIMS.v1.0.x.tgz	+
−	$cd CIMS	+
−	$chmod 755 *.pl	+
−	$mv CIMS /usr/local/CIMS	+
−	</pre>	+
−	Add the dir to your $PATH environment variable.	+	=====Loss of MBNL function leads to disruption of developmentally regulated alternative polyadenylation in RNA-mediated disease=====
−	=CIMS analysis=	+	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.
−	==Input files==	+
−	The key script one needs to run is CIMS.pl, which will take two BED files as input: a list of unique CLIP tags (properly mapped to the reference genome), and the coordinates of mutations (deletions, insertions, or substitutions) in the reference genome and relative the CLIP tags. It is critical to make sure:	+	''Mol Cell.'' 56: 311-322.
−	* analyze one type of mutations at a time.	+	[http://www.ncbi.nlm.nih.gov/pubmed/25263597 PubMed]
−	* the 4th column of the mutation BED file should match the name of the CLIP tag in the first BED file.	+	[http://www.sciencedirect.com/science/article/pii/S1097276514006820/pdfft?md5=c81d51c9f97e8d76d1e21a5c75941edd&pid=1-s2.0-S1097276514006820-main.pdf PDF]
−	* the coordinates of mutations relative to the CLIP tag (from the 5' end of the Watson strand, 0-based) is correctly specified in the 5' column of the second BED file.	+
−	* only mutations in unique CLIP tags should be included.	+
		+	=====An RNA-Sequencing transcriptome and splicing database of glia, neurons, and vascular cells of the cerebral cortex=====
−	Now you can run something like	+	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.
−	perl /usr/local/CIMS/CIMS.pl -v -n 5 -p -FDR 0.001 -c ./cache_del  test.uniq.bed test.uniq.del.bed test.uniq.del.CIMS.txt	+	''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]
−	The output is a list of CIMS at FDR<0.001, one per line.	+	=====HITS-CLIP and integrative modeling define the Rbfox splicing-regulatory network linked to brain development and autism=====
−	The first six columns of this file follow the definition of a BED file, including coordinates and strand of each CIMS. Columns 7-10 are k, m, FDR, and number of sites with m or more tags with mutations given k tags at that position in total (the denominator to calculate FDR, which gives an idea about the precision of the FDR value).	+	<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.
−	This file can be reordered with the following command:	+	''Cell Rep.'' 10.1016/j.celrep.2014.02.005.
−	<pre>	+	[http://www.ncbi.nlm.nih.gov/pubmed/24613350 PubMed]
−	sort test.uniq.del.CIMS.txt -k 9,9n -k 8,8nr -k 7,7n > test.uniq.del.CIMS.sort.txt	+	[http://download.cell.com/cell-reports/pdf/PIIS2211124714000849.pdf PDF]
−	</pre>	+	[http://zhanglab.c2b2.columbia.edu/index.php/CIMS software]
−	==Usage==	+	=====Mapping Argonaute and conventional RNA-binding protein interactions with RNA at single-nucleotide resolution using HITS-CLIP and CIMS analysis=====
−	<pre>	+
−	CIMS.pl [options] <tag.bed> <mutation.bed> <out.txt>	+
−	</pre>	+
−	Arguments:	+	Moore, M.*, <b>Zhang, C.</b>*, Gantman, E.C., Mele, A., Darnell, J.C., Darnell, R.B. 2014.
−	{|class="wikitable" width="100%" style="border:1px solid"	+
−	|-	+
−	!scope="column" width=150|'''Argument'''	+
−	|'''Description'''	+
−	|-	+
−	|<tag.bed>	+
−	|BED file of unique CLIP tags	+
−	|-	+
−	|<mutation.bed>	+
−	|BED file of mutations in unique CLIP tags. Make sure you paid attention to the notes above	+
−	|-	+
−	|<out.txt>	+
−	| output file with the list of CIMS	+
−	|}	+
		+	''Nat Protocols'', 9:263-293.
−	Options:	+	[http://www.ncbi.nlm.nih.gov/pubmed/24407355?dopt=Abstract PubMed]
−	{|class="wikitable" width="100%" style="border:1px solid"	+	[http://www.nature.com/nprot/journal/v9/n2/pdf/nprot.2014.012.pdf PDF]
−	|-	+	[http://zhanglab.c2b2.columbia.edu/index.php/CIMS software]
−	!scope="column" width=150|'''Option'''	+
−	|'''Description'''	+
−	|-	+
−	| -big	+
−	| input files are big (e.g. over 6 million lines)	+
−	|-	+
−	| -n [int]	+
−	|number of iterations for permutation (default: 5)	+
−	|-	+
−	| -p	+
−	| track mutation position relative to read start	+
−	|-	+
−	| --no-sparse-correct	+
−	| no sparcity correction *	+
−	|-	+
−	| -FDR [float]	+
−	| threshold of FDR (default: 1)	+
−	|-	+
−	| -mkr [float]	+
−	| threshold of m-over-k-ratio (default: 0)	+
−	|}	+
−	<nowiki>*</nowiki>This option should not be used in general, but is included to reproduce our earlier analysis.  We introduced this feature to eliminate an additional filtering step based on mutation freqeuncy (i.e., the "m" value).	+	==2013==
−	=CITS analysis=	+	=====Progressive impairment of muscle regeneration in Muscleblind-like 3 isoform knockout mice=====
−	Some variations of CLIP protocols, including BrdU-CLIP and iCLIP allows capture of tags that are truncated at the cross link sites (and those read through as well).  This section describes our method to detect robust cross link induced truncation sites (CITS).	+
−	CITS analysis requires unique CLIP tags as a BED file, which was used to get the coordinates of the potential truncation site, defined as the position immediately upstream of the first nucleotide of the CLIP tag.	+	Poulos, M.G., Batra, R., Li, M., Yuan, Y., <b>Zhang, C.</b>, Darnell, R.B., Swanson, M.S. 2013.
−	<pre>	+	''Hum Mol Genet.'' 22:3547-3558.
−	perl ~/scripts/bedExt.pl -n up -l "-1" -r "-1" -v tag.uniq.bed tag.uniq.trunc.bed	+
−	</pre>	+
		+	[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]
−	Since CLIP tags with cross linking induced mutations (i.e. deletions) most likely represent tags that read through the cross link site, it is recommended that these tags are removed.	+	=====Prediction of clustered RNA-binding protein motif sites in the mammalian genome=====
−	<pre>	+	<b>Zhang, C.</b> †, Lee, K.-Y., Swanson, M.S., Darnell, R.B. † 2013.
−	cut -f 4 tag.uniq.del.bed | sort | uniq > tag.uniq.del.id	+
−	perl ~/scripts/removeRow.pl -q 3 -v tag.uniq.trunc.bed tag.uniq.del.id > tag.uniq.trunc.clean.bed	+
−	</pre>	+
−	We now cluster all CLIP tags. In the next step below, these clusters will be used to shuffle truncation events to evaluate statistical significance of reproducibility.  This is more stringent than gene-based permutation.	+	''Nucleic Acids Res.'' 41:6793-6807.
−	<pre>	+	[http://nar.oxfordjournals.org/content/early/2013/05/17/nar.gkt421.full.pdf PDF]
−	perl ~/scripts/tag2cluster.pl -s -maxgap "-1" -of bed -v tag.uniq.bed tag.uniq.cluster.0.bed	+	[http://zhanglab.c2b2.columbia.edu/index.php/MCarts_Documentation software]
−	awk '{if($5>2) {print $0}}' tag.uniq.cluster.0.bed > tag.uniq.cluster.bed	+
−	</pre>	+
−	<pre>	+	=====OLego: Fast and sensitive mapping of spliced mRNA-Seq reads using small seeds=====
−	perl ~/scripts/tag2peak.pl -ss -v -gap 25 -p 0.001 tag.uniq.cluster.bed tag.uniq.trunc.clean.bed tag.uniq.CITS.s30.bed	+
−	</pre>	+
−	This script will define CITS with p < 0.001 using scan statistics (instead of actually doing random permutation).  Sites within 25 nt will be clustered together.  One might also do Bonforroni multiple testing correction.  If this is the case, use --multi-test.	+	<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]
		+
		+	==2012==
		+
		+
		+
		+	=====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==
		+
		+	=====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.