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BISON: Bio-Interface for the Semi- global analysis
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1. The BISON interface Top left page object information page Top right page network visualization page Bottom page navigation page Legend click upper left A to close go to Graph to re open The navigation bar File lets you select your data directory or exit Graph lets you select the legend choose a layout select edge filters zoom in and out Pattern mining lets you select the pattern mining option Help contains the help function File Graph Pattern Mining Help Legend Opens from the Graph tab The legend explains the nodes and edges Red regulator genes Green target genes Yellow selected gene The four link sources resemble the four net files see pages 8 9 Graph Legend Legend Key QO Regulators O Targets OQ Selected Link Source 1 Link type Link type CANG Link type Link Source 2 Linktvpe Link type Link type Link Source 3 Linktype Link type Link type 4 TT Layout options From the Graph tab You get to select either the Fruchterman Reingold FR layout or the circle layout FH layout Edge filters From the Graph tab You get to select either context edges or incident edges Context edges show the connections between all nodes on the graph Incident edges show only edges leaving or entering the selected node 2j EN p AR Z AI
2. or higher on your computer http www java com Hit Download now and then Begin Download Download the bison1 zip file from Source Code for Biology and Medicine http denton cs ndsu nodak edu bison Extract the files into an uncompressed directory so that the original folders are preserved Select bison1 zip and open Right mouse click bison1 and select extract Choose All files hit extract A new folder will appear on your desktop named bison1 Configuration files Within bison1 the single data directory default data contains two configuration files Edge Color file edgeColors txt BEL RED VALUE GREEN VALUE BLUE VALUE ALPHA DOTTED SOLID 1f Of Of 1f SOLID Of Of 1f 1f DOTTED 1f 1f Of 1f SOLID Configuration file bison config E coli from RegulonDB and Dr Pruess data with annotations from Pfam and Wisconsin GENE ID ENTITYFILE ecoli entity txt ALIASFILE ecoli alias txt SYNONYMFILE ecoli syn txt PATTERNFILE patterns out NETWORKFILE flhD microarray net edgeColors txt NETWORKFILE regulon net edgeColors txt NETWORKFILE pruess net edgeColors txt NETWORKFILE 2component net edgeColors txt LINK http www kegg com dbget bin www_bget eco ID The single data directory default data contains five data input files Data input files Entity file ecoli entity txt lists nodes of the network and the set of properties for each node Alias file ecoli alias txt specifies the default gene names f
3. cellular biosynthesis 0 0 0000E000 n ao bonnie Ok m te 0 10 41 3 _H 1 hmm mepsignal 1 PFOOOIS MethyF ac 5 0 _ S7 0 0000e000 A 4 0 1 tb 1 PF07690 Major_Facilitator_Superfamily 6 0 57 0 0000E000 Mo 4 0 1 1 4 Hil hmm lysr substrate 1 hmm hth 1 0 6 0 57 0 0000E000 K SIS ala A start amp Re latest bison Inb 4 1 IZArc Ew bison 1 0 0 Microsoft PowerPoint amp BISON lt Be 2 17 PM Navigation Select a line from the Descriptor column Gene Centered Pattern Centered Subgraph Links Descriptors 0 1 1 4 1 hmm fla_bb_rod 0 hmm flhd E B H 1 K1 1 hmm pts_eiic 0 hmm fihd 6 H 0 1 Lk 1 hmm response_reg 0 hmm fihd 5 0 1 Wi M hmm bpd transp 1 0 hmm Flhd i 0 1 2 01 t M 1 PFOO84 Molybdopterin oxidoreductase 7 2 0 1 1 1CL hmm abc tran 0 hmm Flhd zB PORT 0 1 um 0 1 0 1 0 1 i i m L4 WD mmm 1 0 h 8 1 _ 1 G0 0044249 celller biosynthesis 0 6 1 _ 1 GO 0005975 carbohydrate_metabolism __6 0 1 D hmm mcsignal D PFOOOIS Methy acc 5 QD 1 _ 1 F07690 Major_Faclitator Superfamiy C 6 OF t D hmmysr substrate D hmm hth D 8 6 Jk Mi MQ 4PFODODS ABC transporter I hmm abc 8 VD M PFODODS ABC transporter I hmm
4. 9 cellular biosynthesis GO 0006519 amino acid and derivative metabolism GO 0044271 nitrogen compound biosynthesis GO 0006082 organic acid metabolism 50002 GO 0016301 kinase activity GO 0019538 protein metabolism GO 0016774 phosphotransferase activity carboxyl group as acceptor hmm homoserine dh GO 0000287 magnesium lon binding hmm nad binding 3 GO 0003959 NADPH dehydrogenase activity GO 0044271 nitrogen compound biosynthesis 30O 0006790 2sulfur metabolism GO 0030554 adenyl nucleotide binding GO 0009308 amine metabolism GO 0006519 amino acid and derivative metabolism GO 0044249 cellular biosynthesis hmm aa kinase GO 0016616 0xidoreductase activity acting on the CH OH group of donors NAD or NADP as acceptor PF00696 Amino acid kinase family GO 0006082 organic acid metabolism Alias file Lists each node from the entify file with the name that should be associated with it 50001 b0002 b0003 b0004 b0005 b0006 b0007 b0008 b0009 60010 thrL thrA thrB thrC yaaX yaaA yaad talB mog yaaH Lists nodes from the entity and alias file that have names associated with them Synonym file in addition to the alias b0116 b0161 b0178 50591 b0755 b1009 b1136 lodA htrA skp ybdA pgmA ycdJ ICAA Pattern file In order to create this file you will have to run the pattern mining engine of BISON see page 18 Lists patterns found with the pattern mining library 0 hmm hatpase c 0
5. BISON Bio Interface for the Semi global analysis Of Network Patterns User Manual Christopher Besemann Anne Denton Nathan J Carr Birgit M Pr f North Dakota State University BISON 1 0 BISON is a software for the analysis of transcriptional networks of regulation It combines a pattern mining engine with modern navigation and network visualization techniques The current default directory of data files contains data from Escherichia coli K 12 BISON enables the user to load their own microarray data into the default directory to be analyzed in the context of the network Data for other species can be loaded into BISON constructing a new file directory Contacts Christopher Besemann and Anne Denton Department of Computer Sciences IACC 258 1301 12 Ave N North Dakota State University Fargo ND 58105 Phone 701 231 6748 E mail Anne Denton ndsu edu Nathan J Carr and Birgit M PruB Department of Veterinary and Microbiological Sciences Van Es Hall 108 1523 Centennial Blvd North Dakota State University Fargo ND 58105 Phone 701 231 7848 E mail Birgit Pruess ndsu edu BISON 1 0 ULL Lam j M oW CM ues oystem Requirements Minimum system requirements System 2 GHz 1 GB of RAM Operating system Windows XP BISON might work with slower processors and other operating systems Loading BISON Installation is not necessary for BISON Install Java 5 0
6. N ji Context edges Incident edges Zoom Select Zoom from the Graph tab On the bottom panel of the Satellite Viewer you can choose between zoom in and zoom out The white window lets you navigate within Satellite Viewer to select your view area This function is particularly useful for networks that contain many nodes Please note that it will be slower then Satellite Viewer Pattern mining Copy the patterns out file to a backup file see page 8 Select Pattern mining from the Graph menu Choose minimum pattern occurrence this is your cutoff for meaningfulness of patterns Choose sub graph file 1 edge indicates two proteins 2 edge indicates three proteins Selecting Compute Significance will run a Chi squared test on the patterns this takes about an hour Hit Compute BISON will now run the pattern library and calculate a new patterns out file You will have to reload the data Resizing the pages Left click and drag the border lines of the network visualization page Gene centered analysis Select the Genes tab in the navigation page Use the Find option to find your gene of interest Click Select in graph Dorma Lao wat for browpa no bead on citano Mg kara begs coc Res hn baa 5251222 2 Tepti Fogidusn i Top left screen the object information page will be the gene information page T
7. abc 5 DY HE HD mm melydep bindng CD hmmamoybd 6 gt Re latest bison Inb 1 IZArc page Il d oO Di pty Gene0 FIhD Pvalue 11 0 0000E000 11 000000 D000E000 Significant 0 0 0000E000 njooo oomoo 0 0000E000 OO00E000 OO00E000 0 0 0 57 0 0000E000 0 0 o 57 0 0000E000 7 7 0000E000 0000E000 247 0 0000E000 O LI CID a ci o hnK f bison 1 0 0 EJ Microsoft PowerPoint amp BISON 8 lt gt 2 20 PM Navigation page ll The right portion of the navigation page now contains two gene lists Gene 0 your gene of interest encodes regulator Gene 1 all the genes that are regulated by your regulator and whose encoded proteins contain the property that is listed in the selected line of the Descriptor column and indicated with 1 This combination of properties is blue on the last slide gt omg o Sa a e a 9 90 0 9 p T d pon D a lt viola 5 ws AAEREN AAE o n A zio 3 3 2 zal zBlzelzelzelzelzelzelzelzelze TITI FF FF FF FI t PowerPoint 2 BISON lt J 2 20 PM Pattern information page Select a line from the Descriptor column auem File Graph Pattern Mining Help Pattern Information The object information page will be the pattern Information page It indicates the patterns involved in this regulation we suggest yo
8. atterns tab Use Filter Patterns option to type in your property of interest This can be a gene name an HMM or other property PF GO Click Filter Patterns Top left screen the object information page will be the gene information page Top right screen network visualization page Bottom screen navigation page Navigation page l The Descriptor column lists properties that are found in your gene as well as in the genes that your gene product regulates 0 indicates properties found in the regulator 1 indicates properties found in the regulated genes The Links column indicates the regulation positive regulation negative regulation The p values are from the Chi squared test Gene Centered Pattern Centered FIhD Filter Patterns Subgraph Links Descriptors o E DF Pvalue Significant 0 1 1 d mm fla bb rod 0 hmm flhd Silica 11 0 0000E000 DF it HC Ahmm pts_ eO meihd 6ft 11o 0oooeooo 1 hmm response_reg 0 hmm fihd S5 i81 11 0 0000E000 GA K e2 up 0 KO 1 4 0 1 1 4 CL hmm bpd transp 1 0 hmm flhd 0 13 1 1 hmm hth_1 0 hmm flhd Fli 0 0000E000 AS e ER O n n T in OD 1k _H 1 hmm abe tran 0 hmm fhd DD Tali 110 0000000 _ KOD 1 9 HC hmm abe kran 0 hmm Ah 7 4 11 00008000 _ OD 1 9 W hmmmfsOMhmmfhd 83 nooo MP 4 0 1 1 4 M 1 GO0 0044249
9. experiment If you just want to add your own microarray experiment with E coli K 12 and analyze it in the context of the network add another network file net to the default data directory in the following format the first column is the regulator gene the second the regulated gene You can collect the data in Excel save it as a tab delimited txt file and change txt to net manually b1892 b0019 b1892 b0020 b1892 60030 b1892 b0032 b1892 b0033 b1892 b0036 b1892 b0037 b1892 b0059 b1892 b0064 b1892 b0066 b1892 b0069 b1892 60070 Add the name of your net file to the bison config file Then load the default_data directory into BISON Adding a new network to BISON If you want to add a whole other organism Create a new directory New data The new data directory will need five data files see page 8 Entity file lists each object node in the network Alias file lists the names each object should be known by Synonym file lists additional names objects may be known by Pattern file contains information gathered by pattern mining routines Network file lists the edges in the network The new data directory will also need two configuration files see page 7 Edgecolor file colors edges in the network Configuration file lists all the files the network builds upon Entity file Lists each node that may be in the network 50001 GO 0009308 amine metabolism GO 004424
10. hmm hiska 1 PF00384 Molybdopterin oxidoreductase 1 hmm molyb dopterin 1 hmm molydop binding 5 0 821119550753283 4 6117 1016 0 PASS 0 1 1 b3404 b0894 b3404 b1224 b3404 b1468 b3911 b1468 b3911 b1224 Lists node pairs from the entity file that form edges in the network b0020 b0020 b0034 b0034 b0034 b0034 b0034 b0034 b0034 b0034 b0034 b0034 b0064 b0064 b0064 b0064 b0064 b0064 b0019 01482 b0035 b0036 b0037 b0038 b0039 b0040 b0041 b0042 b0043 b0044 b0061 b0061 b0062 b0062 b0063 b0063 Network file I t t t t t t NE NE Configuration file termines how to color edges on the networks RED VALUE GREEN VALUE BLUE VALUE ALPHA DOTTED SOLID 1f Of Of 1f SOLID Of Of 1f 1f DOTTED 1f 1f Of 1f SOLID Bison config details Your new data directory must contain a BISON configuration file note that these files will be replaced by your files E coli from RegulonDB and Dr Pruess data with annotations from Pfam and Wisconsin GENE ID ENTITYFILE ecoli entity txt ALIASFILE ecoli alias txt SYNONYMFILE ecoli syn txt PATTERNFILE patterns out NETWORKFILE flhD microarray net edgeColors txt NETWORKFILE regulon net edgeColors txt NETWORKFILE pruess net edgeColors txt NETWORKFILE 2component net edgeColors txt LINK http Wwww kegg com dbget bin www bget eco ID Opening new data Click Bison exe Click File selec
11. op right screen network visualization page Bottom screen navigation page TWh PEELE 21111113 RREH ml Josh Tuan faf we x Navigation page The two tabs are for gene centered and pattern centered analysis Network visualization page Yellow node in center selected gene Hed nodes genes that serve as regulators Green nodes genes that serve as regulated genes Hed solid arrows positive regulation Blue dotted arrows negative regulation Please note for regulators that affect the expression of a large number of genes you will need to use the gene lists in the gene information page for your analysis see next page Also use the Zoom function Indicates properties that are associated with the proteins that are encoded by the selected gene Click the link for more information about this gene You will connect to an external data source Lists all the target genes and the regulator genes of the selected gene Selecting the link for any one of these genes will re form the network visualization page around this gene Gene information page Gene Information emo pm Gene ame fma cene Synonym nene ute 20 Targets 7 Regulatore Targets regulated I elect Cragto Target aer 2 Sect Graph Target che 3 elec in Graph Target cheb 4 5 Target che 8 Select in Graph Target fg 9 rec n Graphi Pattern centered analysis Select the P
12. or the nodes oynonym file ecoli syn txt lists additional names for the nodes Pattern file patterns out stores the patterns of entities and properties discovered in the network Network files net list the edges interactions in the network Please note that the patterns out file is generated by BISON Data regulation Interaction data were integrated into the network files from the following sources Source Interactions Regulators Regulated genes Reference File name RegulonDB 2 537 Salgado et al 2006 regulon net Two comp 1 028 Oshima et al 2002 2component net Compilation 1 969 PruB et al 2006 pruess net FIhD FIhC 896 PruB et al 2003 flhD microarray net Source E coli Genome Project Pfam HMMER Annotations Data properties annotation Proteins 106 2 211 3 124 Reference http www genome wisc edu http www sanger ac uk Software Pfam http hmmer wustl edu Property data were integrated into the entity file from the following sources Designation GO PF HMM Opening BISON Exit Default data directory Click Bison exe Click File select Load File Directory and select Default Data Graph Legend Legend Key Q Regulators e Targets Q Selected Link Source 1 Linktype Link type Link type Link Source 2 Llinktype Link type Link type Link Source 3 Linktype Link type
13. t Load File Directory and select New Data Reference Besemann C Denton A Carr N J and Pr f B M BISON A Bio Interface for the Semi global analysis Of Network patterns 2006 oource Code for Biology and Medicine Volume 1 Please reference this paper when using BISON
14. u resize ioum Pattern by Item List the pages to get the best view at the pattern seo ons ma oe o ate information page ua Gene 0 selected gene encodes regulator nd aria IER Descriptors Descriptors 0 properties found in the regulator jan umma neN nmmabe tran PFOODOSABC transporter 0 wb Gene 1 target genes of the regulator EE Descriptors 1 properties found in the proteins that mmn joo nmmabc tran PFOO005ABC transporter are encoded by the regulated genes mp mmi prov lummabc_tran PF00005 ABC transporter jano hmm frost hmmabe tran PFOOOOSABC transporter mp tumama toC flummabetran PF00005 ABC transporter hrmm abc membrane hmm abc tran PF00005 ABC transporter You can select the Table and use CTRL C to copy the table into a Microsoft Office document Network visualization page Select a line in the Gene column of the navigation page The network visualization page will re arrange around this new gene The object information page will switch to the gene information page and provide you with the information for your newly selected gene Your own data Your own data In addition to the network that is provided with BISON you can add your own data Download detailed instructions from http denton cs ndsu nodak edu bison 32 Adding a microarray
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