overview of subworkflow sketches
Contents
1. additional parameters Are there any additional processes necessary to use the tool Postprocessing After running eHiTS using the command above the conformation with the best score and its score was extracted using a script Network analysis Description of the step Consruction of a drug target network protein graph Tools that participate Analysis O None Use of databases databanks Analysis O Figure None how could this be a sub workflow Draft aproximation Steps 1 Get the output from SMAP step or eHiTS step Fit the number of targets and their connectivity to a power law distribution Build a graph from the drug target network Compute the fraction of the largest connected component by dividing the number of proteins in the largest single linkage cluster by the total number of proteins in the graph How this Method could be linked to other methods subworkflows The input is either obtained from the SMAP step or the eHiTS step nothing is said about the output produced in this step Other questions o Is this step produced manually Ask Lei about this o Is the input taken from the SMAP setp the eHiTS step or other steps o What is the format of the input produced Is it stored somewhere in a table Format AWN o Additional tools used o What is the format of the output Hierarchical clustering of protein and drug binding profiles e Description of the step Hierarchical cluster of the protei2. file in PDB format or SCOP domain code of the 2 entites to compare What are the parameters needed for the tool to work properly No additional parameters are required Can it be run through the command line Apparently Not But it looks like someone just could fill the form automatically submit it and treat the results Is it open source Yes Do I need to install it locally or is it a package library that can download and run Not available to install it locally e Use of databases databanks Analysis o None Steps 1 2 3 4 e Figure how could this be a sub workflow Draft aproximation Query the PDB for the PDB files Are these the same PDB files as in table S4 Use FATCAT to filter the non similar structures Assuming it is table s4 Is each PDB file compared to all the other ones The output would be assuming that we are taking the 749 structures from the PDB in table S4 a file with 794 794 630 436 p values Remove the pairs with high similarity pvalue lt 0 05 e How this Method could be linked to other methods subworkflows O It is not clear how this relates to other sub workflows This step occurs before the SMAP step which uses as input the table S1 How is the list with the non similar structures used later e Other questions O Should ask if they do this step manually or if they access some other service to send multiple queries Check with Sarah I used Andreas JFatCat program Java i
3. uk pub databases chebi or downloaded from the next link http www ebi ac uk chebi downloadsForward do Example of query N A Usage in the step Used for extraction of the names of the active ingredients of the drugs o Table S1 in the Supporting Information Section Information about the approved drug binding sites used in the TB drugome For each drug its name PDB ligand code isomeric SMILES string and known targets are listed and the PDB codes of the protein structures with which it has been crystallized are given Link http Avww ploscompbiol org article fetchSingleRepresentation action uri info doi 10 1371 journal pcbi 1000976 s006 e Figure how could this be a sub workflow Draft aproximation Steps of the task 1 Search for drugs approved by the US and Europe in FDA and EMEA 2 Obtain the names of the active ingredients of the drugs 3 Map the compounds in PubChem DrugBank and ChEBI 4 Remove nutraceuticals and prodrugs 5 Use InChl keys to map the remaining compunds to proteins structures in PDB excluding non protein crystal structures 6 Outcome of the process is table S1 e How this Method could be linked to other methods subworkflows The outcome of this subworkflow is table S1 Still to be seen how it is connected to others e Other questions o Are the InChli keys already provided or are they obtained using their software http www iupac org inchi release102 html Comparison of ligand bind
4. usage from the WS python GenericServiceClient py http kryptonite nbcr net opal2 services SMAPPairComp r launchJob a template_cif_chain a template_pdb_id 1qkt query_cif_chain a query_pdb_id 1ohp VIRTUAL_LIGAND_RANGE_CUTOFF 5 0 LIGAND_CONTACT_DISTANCE_CUTOFF 10 0 SCORE_MATRIX McLACHLAN TEMPLATE_LIGAND_SITE_ONLY false QUERY_LIGAND_SITE_ONLY false Example using the local installation of SMAP http funsite sdsc edu scb smap document himl 20Parameter 20setti ngs o SOIPPA and MWSG algorithms are not described because they are used by the SMAP tool They are not a separate process Use of databases databanks Analysis o None Figure how could this be a sub workflow Draft aproximation Pairs and p values File Table 2222 i l Steps of the task 1 Takes as input table S4 749 proteins the 1446 homology models from table S5 as the first parameter for SMAP The second one is the 962 bindings for the 274 drugs able S4 There is also a script to call the pairs of the proteins 2 Compare the binding sites with the approved drugs in an all against all manner 3 For each pairwise comparison a P value is produced the p value is the probability of obtaining a test statistic at least as extreme as the one that was actually observed assuming that the null hypothesis is true This p value represent the significance of the binding 4 Where is the output located 1 FILE per each pair Additional step to extract all t
5. 5 new Parameter new Parameter input filename new Parameter column distance measure 2 new Parameter row distance measure 0 new Parameter clustering methoa m new Parameter log transform new Parameter row center new Parameter row normalize new Parameter column center new Parameter column normalize new Parameter output base name lt input filename_basename gt Java e Use of databases databanks Analysis o None e Figure how could this be a sub workflow Draft aproximation o There is no need since it is only one step Steps 1 Take the input from SMAP eHITS 2 Use the clustering analysis to make a hierarchy 3 Nothing is said about the output e How this Method could be linked to other methods subworkflows e Other questions Comparison of drug chemical similarity e Description of the step 2D fingerprint similarity e Tools that participate Analysis o OpenBabel 2 1 1 Feature description of the tool http openbabel org wiki Open Babel 2 1 1 chemical toolbox designed to speak the many languages of chemical data The process followed by the tool to produce the expected outcome It gets table S1 drugs assumption as input to calculate the similarity Nothing is said about the output Maybe is it used for another previous step What are the inputs and outputs needed for the tool to work Table S1 What are the parameters needed for the tool to wor
6. Wings Drugome Analysis and extraction of the sub workflows Daniel Garijo amp Yolanda Gil Date 07 09 2011 MM DD YYYY Started 07 05 2011 Analysis of the Methods section of the paper Templates For each Method e Tools that participate Analysis Use of databases databanks Analysis Figure how could this be a sub workflow Draft aproximation How this Method could be linked to other methods subworkflows Other questions For each Tool The analysis of the tools is mainly a Feature description of the tool The process followed by the tool to produce the expected outcome What are the inputs and outputs needed for the tool to work What are the parameters needed for the tool to work properly Can it be run through the command line Is it open source Do need to install it locally or is it a package library that can download and run Example of usage For each Dataset Databank Main features of the dataset databank Is it open access How do query the dataset bank Is there a web service or something like that Can it be accessed remotely Example of query Usage in the step kkkkkkkkkkkkkkkkkkkkkkkkkkkkkkkkkkkkkkkkkkkkkkkkkkkkkkkkkkkkkkkkkkkkkkkkkkkkkkkkkkkkkkkkkkkkkkkkkkkkkkkkkkkkk kkkkkkkkkkkkkkkkkkkkkkkkkkkkkkkkkkkkkkkkkkkkkkkkkkkkkkkkkkkkkkkkkkkkkkkkkkkkkkkkkkkkkkkkkkkkkkkkkkkkkkkkkkkkk kkkkkkkk Structural coverage of the M tb proteome e Description of the method In this s
7. are the inputs and outputs needed for the tool to work Assumption The significance value of the pairs analyzed with the SMAP tool What are the parameters needed for the tool to work properly I had no access to the user manual Can it be run through the command line ask the authors of the study ask for a demo Yes e g ehits sh receptor receptor_file pdb clip clip_file ligand ligand_file pdb workdir accuracy 6 out output_file sdf Is it open source No you have to request for a demo and then purchase the product Do I need to install it locally or is ita package library that can download and run Local install Example of usage N A there is no documentation without a registration e Use of databases databanks Analysis o None e Figure how could this be a sub workflow Draft aproximation Steps 1 2 3 4 Take the output produced by SMAP For those proteins with cofactors add the cofactor as the last residue in the protein Parameters search space of 10A 3 accuracy level 6 eHiTS outcome is produced as a SDF file with the resulting conformations of the molecule and their corresponding energy scores How this Method could be linked to other methods subworkflows Takes as input the output produced by SMAP Nothing is said about the outcome produced Other questions O Ask the authors about the eHiTS tool Is it used automatically What is the format of the outcome Are there any
8. cle fetchSingleRepresentation action uri info doi 10 1371 journal pcbi 1000976 s010 e Figure how could this be a sub workflow Draft aproximation Steps of the task 1 NOAROND Look up in PDB the proteins of the M tb proteome with solved structures Select the multiple structures available for the proteins The outcome of this is table S4 Look up in ModBase the homology models of the proteome Assign to each of them the MPQS Select the models with MPQS gt 1 1 The outcome of this process is table S5 e How this Method could be linked to other methods subworkflows The outcomes produced by this subworkflow are 2 table S4 and table S5 e Additional questions o How is this step done manually o The access to ModBase how is it done I just downloaded the flat files from the database and parsed them using a script o The MPQS assignation is done manually or there is an additional script tool The MPQS was extracted from the flat files Identification of FDA approved drug binding sites e Description of this step In this step takes place the selection of the approved drugs binding sites in the United States and Europe used in the study e Tools that participate Analysis o None e Use of databases databanks Analysis o Food And Drug Administration Orange Book Main features of the dataset databank http www accessdata fda gov scripts cder ob default cfm Drugs for human use Is it open access Yes How do que
9. d http oubchem ncbi nim nih gov idexchange idexchange cqi Can it be accessed remotely ftp ftp ftp ncbi nlm nih gov pubchem bulk data download Example of query N A Usage in the step Used for extraction of the names of the active ingredients of the drugs o DrugBank Main features of the dataset databank Combines detailed drug i e chemical pharmacological and pharmaceutical data with comprehensive drug target i e sequence structure and pathway information Is it open access Yes How do I query the dataset bank Via the web page http Awww drugbank ca extractor Results can be shown in various formats HTML CSV Text query is also possible http Awww drugbank ca search advanced Example of query N A Can it be accessed remotely It can be downloaded http Awww drugbank ca downloads Usage in the step Used for extraction of the names of the active ingredients of the drugs o ChEBI Main features of the dataset databank http www ebi ac uk chebi Stands for Chemical Entities of Biological Interest ChEBI Centered in small molecular entity groups It also provides an ontological classification capturing the relationships between entity classes and their parents childs Is it open access Yes How do I query the dataset Via the web page http www ebi ac uk chebi init do or http www ebi ac uk chebi advancedSearchForward do advanced search Can it be accessed remotely lt can be accessed via ftp ftp ftp ebi ac
10. ded as a xls sheet Example of query N A Usage in the step Used to calculate the in vitro essentiality with the COBRA Toolbox e Figure how could this be a sub workflow Draft aproximation Steps i Use GSMN Tb to carry out the FBA computations Use the single gene knockout tool to run essentiality prediction Constrain some genes in order to simulate multiple gene knockouts Use iNJ661 as input to the COBRA Toolbox to perform single gene deletions and determine in vitro essentiality e How this Method could be linked to other methods subworkflows it is defined as an independent step e Other questions Molecular docking using eHiTS e Description of the step in this step molecular docking to predict the binding pose and affinity of the drug molecule to the drug proteine takes place using eHiTS e Tools that participate Analysis o New tool for doing the docking Autodock vina They have scripts for running it o eHITS Lightning Feature description of the tool http Wwww simbiosys com ehits ehits benefits html According to the web page Fast accurate full automated customizable tool used for docking studies The process followed by the tool to produce the expected outcome Takes the input produced by the SMAP tool For those proteins with cofactors the cofactor was added as the last residue in the protein structure prior to docking Nothing is said about the outcome produced by the tool What
11. he values and drop them into a table They have a script so we would need it PERL scripts How this Method could be linked to other methods subworkflows It uses the outcome of the previous 2 sub workflows as the input to make the comparison and produce the p values I assume that the output from the SMAP tool is a list of p value result one for each comparison this is not specified in the paper It would be a list of 2195 962 2 111 590 entries or a table of 2195 rows and 962 columns Comparison of global protein structures using FATCAT e Description of the step In this step takes place the use of FATCAT e Tools that participate Analysis o FATCAT Feature description of the tool Flexible structure AlignemenT by Chaining Aligned fragment pairs allowing Twists It is used to report the overall similarity between 2 structures using a p value to measure it P value less than 0 05 means that they are similar The process followed by the tool to produce the expected outcome The user fills a form providing either the PDB code file in PDB format or SCOP domain code of the two resources to be aligned and submits it to the server The response is a p value with the similarity and some additional outcomes from the server Example http fatcat burnham org fatcat examples iufhA igheA Form available at http fatcat burnham org fatcat cgi cgi fatcat pl func pairwise What are the inputs and outputs needed for the tool to work PDB code
12. ing sites using SMAP e Description of the step In this step SMAP tool is used to compare the binding sites of of the 749 protein structures 1446 homology models with the 962 binding sites of the 274 approved drugs The outcome is a p value for each pair compared e Tools that participate Analysis o SMAP Features of the tool designed for the comparison and the similarity search of protein three dimensional motifs independent on the sequence order The process followed by the tool to produce the expected outcome Based on a sequence order independent profile profile alignement SOIPPA algorithm It also uses the MWSG algorithm to align two protein structures using a maximum weighed sub graph What are the inputs and outputs needed for the tool to work It requires 2 structures For each it is required 1 PDB ID or PDB File 2 Chain ID What are the parameters needed for the tool to work properly All the parameters are specified at http nbcr sdsc edu pub wiki index php title SMAP Opal Services Prog rammatic Access Can it be run through the command line It offers a WS accesible programatically http nbcr sdsc edu pub wiki index php title SMAP Opal Services Prog rammatic_ Access It can also be downloaded Is it open source Yes Do I need to install it locally or is it a package library that can download and run can download it from http funsite sdsc edu scb smap document html 20Installation Installation instructions Example of
13. k nteraction Networki Interaction Network ll FIRST STEPS Table 1 Filtered drug binding sites Raw Network nteraction Network Interaction Network
14. k properly Can it be run through the command line Yes The obabel command line program converts chemical objects currently molecules or reactions from one file format to another The GUI interface is an alternative to using the command line and has the same capabilities Is it open source Yes Do I need to install it locally or is ita package library that can download and run Libraries can be used from Java http openbabel org docs 2 3 0 Use TheLibrary Java html Example of usage The link above covers them They can be found in the tutorials too http openbabel org wiki Tutorial Fingerprints Eg PROMPT gt babel L fingerprints e Use of databases databanks Analysis o None e Figure how could this be a sub workflow Draft aproximation o There is no need since it is just one step Steps 1 Input Table S1 2 Process OpenBabel 3 Output e How this Method could be linked to other methods subworkflows Nothing is said in the step e Other questions o How is the output of this method used for other methods Additional steps files http funsite sdsc edu drugome TB Summary Overview connection between all the methods Table S4 Table 4 55 Table 1 Table S1 SMAP Output not sure not sure not sure SMAP Output Overview connection between all the methods FIX Table 54 55 Table S14 ll Table S4 S5 Filtered drug binding sites Raw Networ
15. mplementation of FATCAT The PDB files mentioned in the paper is it a reference to table s4 if not which other PDB files are they referring to in this step Visualization of the protein drug interaction network e Description of the step This step describes the use of yEd as a Graphical editor to visualize the protein drug interaction e Tools that participate Analysis o yEd Graph Editor Feature description of the tool Diagram editor The process followed by the tool to produce the expected outcome N A What are the inputs and outputs needed for the tool to work The network from FATCAT A Formatting is required in order to represent the network with yEd Cytoscape could be an alternative Check with Lei and Sarah if they have it wrote a script to generate the input for yEd in the correct format What are the parameters needed for the tool to work properly N A Can it be run through the command line Yed uses a graphical interface It can not be run directly with the command line In fact it is not allowed Clarifies that using yEd as part of an automated process is not allowed Is it open source It is free but not open source Do I need to install it locally or is ita package library that can download and run You need to install it locally Example of usage N A e Use of databases databanks Analysis o NCBI Entrez Main features of the dataset databank collection of sequences from several sources including translations from an
16. n and drug binding profiles using GenePattern 2 0 e Tools that participate Analysis o GenePattern 2 0 Feature description of the tool genomic analysis platform that provides access to more than 150 tools for gene expression analysis proteomics SNP analysis flow cytometry RNA seq analysis and common data processing tasks The process followed by the tool to produce the expected outcome assume it takes the result from eHiTS or SMAP as input file What are the inputs and outputs needed for the tool to work What are the parameters needed for the tool to work properly The parameter is the city block distance Can it be run through the command line It looks that it can be directly accessed from Java and Matlab http Awww broadinstitute org cancer software genepattern tutorial go pro grammer html Matlab_doc Using GenePattern from Java Libraries available at http qgenepattern broadinstitute org go pages downloadProgrammingLiba ries jsf Is it open source It is free but believe is not open Do need to install it locally or is ita package library that can download and run You can either http www broadinstitute org cancer software genepattern installer latest i nstall htm Setting up your own server or use the website login required http genepattern broadinstitute org gp pages index jsf Example of usage JobResult result gpClient runAnalysis urn lsid broad mit edu cancer software genepattern module analysis 00009
17. notated coding regions in GenBank RefSeq and TPA as well as records from SwissProt PIR PRF and PDB Is it open access YES How do query the dataset bank Is there a web service or something like that It offers a web access to the database filling a form or by key words htto Awww ncbi nim nih gov oooks NBK44863 FTP ftp fto ncbi nim nih gov genbank ftp ftp ncbi nih gov refseq Can it be accessed remotely I haven t found any other remote access MANUALLY by filling a form Maybe we can automatize this writing a component Example of query N A Usage in the step To query the names of the M tb proteins in order to avoid inconsistences with the naming proteins of the PDB e Figure how could this be a sub workflow Draft aproximation o No need to represent the workflow for this task I think Steps 1 Assumption Treat the information produced by SMAP into a table Matrix so it can be read directly by yEd 2 Query the M tb protein names to the Entres protein database 3 Represent the graph using yEd How this Method could be linked to other methods subworkflows The input used for the graph representation is the same one produced by SMAP Other questions What is the input received by yEd I have assumed it is the one from SMAP Is this process necessary for the study or for just seeing the results How is this step linked to other parts of the workflow Flux balance analysis Description of the ste
18. own Use of databases databanks Analysis GSMN TB Main features of the dataset databank Web based genome scale network model used to carry out the flux balance analysis Is it open access Yes How do query the dataset bank Is there a web service or something like that http sysbio3 fhms surrey ac uk cqi O bin fba foapy model GSMN_TB Viv amp cmd methods A web form based query is the only available way to use the service It can be modified http sysbio3 fhms surrey ac uk cqi bin foa foapy model GSMN_TB Viv amp cmd fba Can it be accessed remotely Aparently not Have the authors accessed in some other direct way No it was just accessed using the web This didn t matter as it was only for a small number of genes Example of query http sysbio3 fhms surrey ac uk cgi bin fba foapy model GSMN_TB Viv amp cmd fba already shows a query It returns a file like this showing the FBA http sysbio3 fhms surrey ac uk cqi bin fba foapy sid sid5008843 amp cmd showfba amp model GSMN_TB Viv Usage in the step This model is used to calculate the essentiality prediction under conditions optimized for in vivo growth iNJ661 Main features of the dataset databank Is it open access Yes How do query the dataset bank Is there a web service or something like that It can be downloaded through the next link http Avww biomedcentral com 1752 0509 1 26 additional Can it be accessed remotely There is no need it can be downloa
19. p In this step both the in vivo essentiality and the in vitro essentiality are calculated using different toolboxes and databases I assume that non essential genes are discarded Tools that participate Analysis COBRA Toolbox Feature description of the tool http opencobra sourceforge net openCOBRA Welcome html Constraints Based Reconstruction and Analysis COBRA focuses on employing physicochemical constraints to define the set of feasible states for a biological network in a given condition based on current knowledge The process followed by the tool to produce the expected outcome It is used to delete single genes on the iNJ661 model What are the inputs and outputs needed for the tool to work It uses the iNJ661 model grown in 7H9 media No additional information is provided How is the iNJ661 used which functions scripts of the COBRA Toolbox are used What are the parameters needed for the tool to work properly Installations instructions usage available at http Avww nature com protocolexchange protocols 2097 procedure Can it be run through the command line Yes because they are Matlab scripts Is it open source NO It is designed to run with Matlab which is not open source However the toolbox is free Do I need to install it locally or is ita package library that can download and run Local install Matlab Cobra toolbox download Example of usage N A since the methods of the toolbox used for the study are not kn
20. ry it They have a Web page in http www accessdata fda gov scripts cder ob default cfm Can it be accessed remotely There is no need it can be downoladed from http www fda gov Drugs InformationOnDrugs ucm129689 htm Example of query N A direct usage of the web service Usage in the step Query to retrieve the drugs for human use in the US o European Medicines Agency Main features of the dataset databank http www ema europa eu ema Drugs for human use in Europe Monitorized safety of the drugs in the dataset Is it open access Yes How do query the dataset bank Via the frontend exposed at http Awww ema europa eu ema Can it be accessed remotely There is no need It can be downloaded from http Avww ema europa eu ema index jsp curl pages document library d ocument _listing document listing 000312 jso amp murl menus document lib rary document _library jso amp mid WC0b01ac0580022517 Example of query N A since it is done providing the medicine name at the web page Usage in the step Query to retrieve the available drugs for human use in Europe o PubChem Main features of the dataset databank http oubchem ncbi nim nih gov Provides information on the biological activities of small molecules and it is organized as three diferent linked datasets Substance Compbound and BioAssay Is it open access Yes How do query the dataset bank Via its frontend http oubchem ncbi nlm nih gov Lists of IDs can also be querie
21. tep takes place the selection of the proteins and the homology models to be used in the study e Tools that participate Analysis o None e Use of databases databanks Analysis o RCSB PDB Research Collaboratory for Structural Bioinformatics Protein Data Bank http www pdb org pdb home home do Features The Protein Data Bank PDB archive is the single worldwide repository of information about the 3D structures of large biological molecules including proteins and nucleic acids Is it Open Yes free of all copyright restrictions and made fully and freely available for both non commercial and commercial use How to query it the website http www pdb org pdb search advSearch do ftp server Supporting ftp and rsync access ftp ftp wwpdb org Web Services and RSS feeds Can it be accessed remotely YES http Awww pdb org pdb software rest do Query example In the website you can enter a protein ID and search the results It can be also visualized in 3D with some java applets Usage in this step Find which proteins in the M tb proteome have solved structures in the RCSD PDB o ModBase homology models http modbase compbio ucsf edu modbase cqi index cgi Features queryable database of annotated protein structure models MODBASE contains theoretically calculated models which may contain significant errors not experimentally determined structures Open Yes Users of ModBase must cite a specific paper in their publications Ho
22. w to query it ModBase Search form http modbase compbio ucsf edu modbase cgi index cgi Login requested for advanced features Can it be accessed remotely I haven t found any web services to access it Query example No need since it is donde with the graphical interface Usage in this step ModBase is used as the database where the homology models for the M tb proteome have been retrieved Each model is assigned a ModPipe Protein Quality Score and if this score is greater than 1 1 then the model can be considered reliable MPQS is a composite score comprising sequence identity to the template coverage and the three individual scores evalue z Dope and GA341 We consider a MPQS of gt 1 1 as reliable A total of 1446 reliable homology models have been selected o Table S4 in the Supporting Information section O Information about the solved M tb structures used in the TB drugome For each protein the gene name if available gene accession number protein name and corresponding PDB codes are given Link to the sheet http www ploscompbiol org article fetchSingleRepresentation action uri info doi 10 1371 journal pcbi 1000976 s009 Table S5 in the Supporting Information section Information about the M tb homology models used in the TB drugome For each homology model the ModBase model code is given as well as the gene accession number gene name and description of the M tb protein N B Link http www ploscompbiol org arti
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