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GoView and GoGet User Manual

1. p lt OUT ZoomBar IN gt View selected Terms in goGet Subgraph function positive regulation of cell growth SS cell growth interpretation of extern signals that regulate SS cell growth negative regulation of EEE EEE gt Figure 14 A snapshot of GoView displaying the cell growth subgraph Once you have selected regulation of cell growth click on the button View Selected Terms in goGet situated on the lower left corner This will open up GoGet in a web browser window with more information on regulation of cell Growth as shown in Figure 15 Before clicking make sure that you have selected a browser The browser that work best with this is mozilla Before selecting a browser make sure that all of your mozilla or safari browsers are closed After closing your browser click on edit at the top of the page then select properties A small window should open Then select select and it should open the applications page which contains mozilla If you are using linux operating systems find mozilla s path and copy and paste in into the text field by browser 22 MacGO goGet and GoView connection Mozilla File Edit View Go Bookmarks Tools Window Help 4 2 23 a CEM m x k Kis http db math macalester edu GoProject connect jsp goview_call minus math
2. and or But Not Term Gene Product 7 Full Name Symbol Contains Partially Synonym C contains Exactly What is Gene Ontology Copyright 2003 Macalester College Valid HTML 4 01 Valid CSS2 Figure 25 Opening view of GoGet 4 2 1 Ontologies In the Ontologies field check which of the three ontologies to search Select one or more ontology by clicking the check boxes on the left 4 2 2 Using Set 1 Inside a set there are a maximum of two text fields you can search You can choose to search terms or gene products for each of these fields Check the term radio button if you wish to search the terms Select if you would like to search the term names their definitions and or their synonyms by checking one or more check boxes Type in the word or phrase you would like to search for Check the gene product radio box if you wish to search by the gene products Select if you would like to search the gene products full name their symbol and or their synonyms by checking one or more check boxes Type in the word or phrase you would like to search for If you use both fields select And Or or But Not by marking the radio box 35 And will only return gene product term pairs the meet the criteria on both sides of the and If you searched DNA binding in terms and DNA repair in gene products it will return only gene products that have DNA repair in the selected gene product fields and are associa
3. Now lets play with the zoom a bit Figure 20 External encapsulating structure graph Using either the lt Out button or the zoom slider bar to zoom all the way in on the graph Full zoom out is shown in Figure 21 Molecular Functions e al Cellular Component J i external encapsulating structu v Figure 21 Zoom out Zoom back in a bit and select all the terms in the last two columns of nodes in the graph as shown in Figure 22 29 GoView ______________ Done Pick a new graph or explore this one Molecular Functions Biological Processes Gell Teel projection CellularComponent cellular_component unknown cell surface extracellular external encapsulating structure immunoglobulin complex immature spore obsolete cellular component intracellular unlocalized membrane virion midbody periplasmic space Close Graph X cell growth X extracellular X external encapsulating structure S S layer slime layer Ni _ _ oalye lignin network Casparian stip ___ capsule sensu Bacteria pse er capsule sensu Fungi secondarycell wall Sapte ena Fund _ oo eee exracellularmarix prmarycet wat gt primarycell wall a sensu Magnoliophyta aa cell wall sensu Magnoliophyta aaaea D _ wa E call wall sensu Fun
4. Refining your search There are some other choices that you can use to refine your search further The buttons at the top of the results page enable you to bring back the boxes that you used when you formulated your search initially Choose the All button to bring back all of the search options as shown in Figure 4 Each of the buttons to the left of the All button will pop up the individual filtering options and search set options Notice that these are toggles and if you click All again the choices go away and you can still see the results from your last query MacGO goGet Mozilla lologies 1 set2 Data Sources Evidenc e Types My Search Search Within results Clear 2 Evidence Types Ontologies Data Sources V Molecular Function v All v All V Bological Process V TIGR_CMR The Institute for Genomic Research v TAS traceable author statement V Cellular Component Comprehensive Microbial Resource V IEA inferred from electronic c Tyu V RGD Rat Genome Database annotation v GeneDB_Tbrucei GeneDB_Tbrucei Jv NR not recorded V WB WormBase database of nematode biology v ISS inferred from sequence or V MGI Mouse Genome Informatics Structural similarity GeneDB_Gmorsitans GeneDB_Gmorsitans Jv IDA inferred from direct eee J Synonym Contains Exactly gt ZFIN The Zebrafish Information Network Vv S from
5. RGD Gene Report Cish Mozilla Hx X Eile Edit View Go Bookmarks Tools Window Help ae Je 2 2 B Hirgd mew iew cgi id 5 fil Back Reload amp http rgd mew edurtools genes genes_view cgi id 69261 z s2 Search F m T Home wf Bookmarks 4 The Mozilla Organiza g Latest Builds l Ay A x S for wildcard co fil e ai Ji FEM Advanced Search Rat Genome Database css Home Data Tools Rat Community Download Submit Data Contact About RGD Help Links Genes atts Strains ontologies SSLPs ESTs Sequences taps References Homologs Lalerpel serats Gene Ontology s Gene Report Cish Related Sites Ra gt oe Symbol Cish TIGR Gene Index Full Name cytokine inducible SH2 containing protein Previous name cytokine inducible SH2 containing protein cytokine inducible SH2 containing protein 1 View Homologs 2 found mRNA AF065161 Ontology Term Evidence Reference Biological Process cytokine and chemokine mediated signaling pathway IEP 724748 intracellular signaling cascade IEA 727223 regulation of cell growth IEA 727223 signal transduction IEA 727223 zl EA F Figure 19 Rat genome database web page for a specific gene product 3 7 Getting multiple nodes from GoView and The GoView Application Connection Go back into Go View If you wish you can close the cell growth graph by hitting the close graph button on the upper right above the readable graph or by choosin
6. GeneDB_Lmajor GeneDB_Lmajor GeneDB_Lmajor DDB DictyBase DDB DictyBase FB FlyBase FB FlyBase GR Gramene A GR Gramene A 4 ia Comparative Mapping Comparative Mapping v 4 gt Close Search 2 Eb w ES GZ Done H F Figure 12 Choosing terms that have mouse gene products but not friutfly gene products Pick MGI Mouse Genome Informatics from the left hand list but not between the two lists and FB Flybase from the right hand list What you are asking for by doing this is those terms from the ones you selected that have mouse gene products associated to them but do not have friutfly gene products associated to them Note that the latest version of the GO database now has species data for each gene product in addition to the data source We plan to use that in the future to help you formulate this question and get more accurate results Pick the Search button at the bottom of the blue box where you chose the two data sources This type of database query takes a fair amount of time to execute so you will need to wait a couple of minutes What is returned is two of the terms and the gene products associated with them as of the May 2004 version of the GO database Using this same analysis box you can also ask for those terms which have both mouse and fruitfly gene products associated to them AND choice or you can ask for those terms that have either mouse or fruitfly gen
7. GeneDB_Spombe GeneDB_Spombe V Name DNA binding Definition Contains Partially J Synonym Contains Exactly Return gene products whose full name partly contains repair in terms whose name partly contains DNA binding but do not include gene products whose full name partly contains replication in terms whose name partly contains DNA binding in all ontologies in all data sources and in all evidence types and Or But Not Term Gene Product v Full Name replication Symbol Contains Partially rr Synonym Contains Exactly What is Gene Ontology Copyright 2003 Macalester College Valid HTML 4 01 Valid CSS2 3 GL w ES Done H a Figure 9 Completed example using set 1 and set 2 Searching Tips This seems like a search that could be worded any number of ways but this is not the case this specific setup is necessary for it to give the results that are most likely desired from the original English query DNA binding proteins that are involved in DNA repair but not involved in DNA replication The set 1 part of the query gives us a list of gene products that involve repair that are associated with DNA binding terms technically it is a set of gene products whose name contains the text repair We then subtract any replication gene products that also have associations to DNA binding terms As a check for what is going on you can try just searching for DNA binding terms
8. button pick Term then pick only name and type in regulation of cell growth in place of the default triphosphatase This is a step that we will eventually remove as we realize that it s a bit awkward and doesn t work well when you ve chosen multiple terms to send to GoGet Choose the Data Sources button select All to toggle off all of the data sources then pick the Rat Genome Database You should get a smaller number of gene products as shown in Figure 17 MacGO goGet and GoView connection Mozilla x Eile Edit View Go Bookmarks Tools Window Help z 2 F a X 2 3 a http db math macalester edu GaProject connectjsp goview_calleminus math macalesteredu gt s2 Search Sd w Back Reload Print Home wf Bookmarks gThe Mozilla Organiza Latest Builds Ontologies Set 1 Set 2 Data Sources Evidence Types My Search All Search Within results Clear ud Search terms which have Rat Genome Database but not Mouse Genome Informatics gene products associated with it from the set of terms regulation of cell growth Results Click here to analyze results Term Name ACC gt All Definition Ontology Term Synonyms Gene Products information of gene products 1558 regulation of cell growth biological_process inone display What is Gene Ontology Copyright 2003 Macalester College Valid HTML 4 01 Valid CSS
9. link and GoGet will come up in its own window We make a lot of use of cascading style sheets in our HTML some of which is not always displayed properly on all browsers We have had the best luck with Mozilla and Mozilla Firefox on all platforms and fairly good luck with Safari on Mac OS X We are still working on how to improve the layout and functionality under Internet Explorer for Windows so if this is your only browser option some things may not look just like the figures in this document AS an initial introduction to the GoGet searching tool we will show you a relatively simple example and describe the features of the interface The tool initially looks like Figure 1 MacGO goGet Mozilla Ontologies Set 1 Set 2 Data Sources Ontologies Jv Molecular Function v Bological Process V Cellular Component Term Gene Product v Name riphosphatase Definition Contains Partially I Synonym Contains Exactly and Or But Not Term Gene Product Full Name Symbol Contains Partially L Synonym Contains Exactly and Or But Not Term Gene Product Full Name Symbol Contains Partially LI Synonym Contains Exactly and Or But Not Term Gene Product 7 Full Name J Symbol Contains Partially L Synonym Contains Exactly 3h EL w EJ Done Figure 1 The tool has several differ
10. ynony Contains Exactly E an The Arabidopsis Information ue i gt lEP inferred from expression pattern e And C Or e But Not E ee See ae for Genomic Research Arabidopsis Iv MP inferred from mutant phenotype Term Gene Product E tigr_cmr The Institute for Genomic Research m C inferred by curator Full Name Pax6 Comprehensive Microbial Resource j NAS non traceable author statement 7 Symbol Contains Partially E pompep Schizosaccharomyces pompbe protein data E FPI inferred from physical interation J Synonym C Contains Exactly rod Rat Genome Database V ND no biological data available ae ee AE tr EMBL IGI inferred from genetic interation E tgi The Institute for Genomic Research TIGR Gene Index M sgd Saccharomyces Genome Database and C or But Not Term Gene Product Name Definition Contains Partially Return gene products whose symbol partly contains Pax6 in terms whose M Synonym C Contains Exactly name partly contains eye morphogenesis in all ontologies in mgi data source and in all evidence types and Or But Not Term Gene Product Full Name J Symbol Contains Partially i Synonym C Contains Exactly What is Gene Ontology Copyright 2003 Macalester College Valid HTML 4 01 Valid CSS2 eB be elm OOOO EO OOOO PE Figure 6 Combining term and gene product search and data source filtering 12 To initiate the
11. Types Jv Molecular Function v All jv All v Bological Process V TIGR_CMR The Institute for Genomic Research v TAS traceable author statement V Cellular Component Comprehensive Microbial Resource V IEA inferred from electronic V RGD Rat Genome Database annotation v GeneDB_Tbrucei GeneDB_Tbrucei Jv NR not recorded Term Gene Product V WB WormBase database of nematode biology 7 ISS inferred from sequence or Jv Name DNA binding V MGI Mouse Genome Informatics structural similarity Definition Contains Partially 7 GeneDB_Gmorsitans GeneDB_Gmorsitans V IDA inferred from direct assay J Synonym Contains Exactly V ZFIN The Zebrafish Information Network a i a from expression ang Or But Not a GeneDE_Lmajor GeneDB_Lmajor V IMP inferred from mutant v DDB DictyBase phenotype Term Gene Product V FB FlyBase IC inferred by curator v Full Name v Shl Gramene A Comparative Mapping Resource for V NAS non traceable author eo 5 rains statement E irae e Cones aa v TAIR The Arabidopsis Information Resource Jv IPI inferred from physical Contains Exactly V UniProt The Universal Protein Knowledgebase interaction ana Or But Not v TIGR_TGI The Institute for Genomic Research V ND no biological data available TIGR Gene Index V IGI inferred from genetic interaction Term Gene Product SGD Saccharomyces Genome Database a Jv
12. are also in the extracellular graph If you chose one of those from the list the graph will center on that term Try closing the graph by clicking on the Close Graph button 31 or the X in the tab and than clicking on a member of that graph Notice that the graph comes back up again with the term you chose centered NOTE The first time you bring up a graph with a term it may not center on that term Just click it again in the list and it will Sometimes Java graphical user interface programming can be painful and produce odd results that are difficult to do much about We ve presented a few features of each of the two tools and shown how they can be used together We hope that you have fun with them and we are always open to suggestions which can be sent to goproject macalester edu 32 4 0 Reference This section should be used as a reference for the specific functions of aspects of the programs after going through the tutorial The information in GoGet can be accessed in two ways Finding terms on a GoView graph or searching using GoGet search tools 4 1 Exploring GoView 4 1 1 Opening a graph Once GoView is open chose between Molecular Functions Biological Processes and Cellular Components in the upper left corner of the screen Clicking on the one of these three will bring up a list of graphs from this Ontology To see the graph of a member of this list click on it Components Functions or Processes with an asteris
13. by repeating this process If you only open up one term in the GoView Application Connection you will only be able to center the graph on that term once but if you add more terms you will be able to do it indefinitely If you close this window it can be opened again by going to View gt Open Graph List This tool is also useful for finding terms on the graphs that we located in a GoGet search If we know a term and we want to see how it fits in the graph we can search for its name in GoGet and then use this tool to find it on the graphs 40 5 0 Contacting Us and Acknowledgments This is a new project and any questions comments and suggestions are welcome Contact us at goproject macalester edu This project was primarily the work of the following Macalester students Paulo Casaes Getiria Onsongo Lisa Lesnett Dennis Tkach Erla Osk Petursdottir Edward Kofi Yeboah Donkor Michael Cosimini Nyalleng Moorosi Daniel Feldman and Elizabeth Gabriel 6 0 Bibliography Ashburner M Ball C Blake J Botstein D Butler H Cherry J Davis A Dolinski K Dwight S Eppig J Harris M Hill D Issel Tarver L Kasarskis A Lewis S Matese J Richardson J Ringwald M Rubin G and Sherlock G 2000 Gene ontology tool for the unification of biology the Gene Ontology Consortium Nat Genet 25 1 25 29 Ashburner M and Lewis S 2002 On ontologies for biologists the gene ontology untangling the web I
14. have NTP in their full names Try this and see what happens If you try Or between the term and Gene Product search choices you would get all terms with triphosphatase in their names and in addition all terms whose associated gene products happen to have NTP in their name This combination using Or might not always be what you re looking for It is there mainly for when you might choose to search for terms with one phrase or another in it you pick Term in each case Please try this on your own 10 AAA MacGO goGet Mozilla Ontologies sett set2 Data Sources Evidence Types My Search Search Within results Clear E Ontologies Data Sources Evidence Types 3 whose full name part V Molecular Function Ince types within the v Al s v All V Bological Process jources and in all evid V TIGR_CMR The Institute for Genomic Research Jv TAS traceable author statement V Cellular Component Comprehensive Microbial Resource V IEA inferred from electronic V RGD Rat Genome Database annotation E e v GeneDB_Tbrucei GeneDB_Tbrucei V NR not recorded Ls eon V WB WormBase database of nematode biology Jv ISS inferred from sequence or Iv st eh ili alas V MGI Mouse Genome Informatics ete similarity Definition Contains Partially v GeneDB_Gmorsitans GeneDB_Gmorsitans V IDA inferred from direct assay V IEP inferred from expression
15. involved in DNA repair but not involved in DNA replication One way to think about doing this is to consider the two parts 1 DNA binding proteins involved in repair and 2 DNA binding proteins involved in replication These two sets overlap since some proteins gene products might have both repair and replication functions Thus subtracting the second set 2 from the first set 1 should give us what we are looking for Steps for this query Without closing the results window click All and then Clear Then select the Term radio box on the top of Set 1 Check the name box and type in DNA binding in the text field Next make sure the And radio button is selected inside of set 1 14 Select the Gene Product radio box on the bottom of set 1 Click the full name radio box and type out repair in the text field Next select the And radio box in the middle of set 2 Then select Gene Product in the lower field and then select the full name checkbox Type replication in to the text field Now select the But not radio box between the two sets Your query should look like Figure 9 Click search Because this is a slightly more complicated search it will take about a minute to return the results AAA MacGO goGet Mozilla S _ Ontologies sett set2 Data Sources Evidence Types i My Search a Search Clear 2 Ontologies Data Sources Evidence
16. macalesteredu v s2 Search FE X m i rin Reload Ak Home wf Bookmarks gThe Mozilla Organiza g Latest Builds Ontologies Set 1 Set 2 Data Sources Evidence Types My Search All Search Within results Clear Search from GoView Results Click here to analyze results Gene Products information of gene products Term Name on I Definition Ontology Term Synonyms ace 1 r regulation of cell growth display biolagical_process jinone dy E What is Gene Ontology Copyright 2003 Macalester College Valid HTML 4 01 Valid CSS2 T5 06 17 04 Figure 15 GoGet when called from GoView Notice that it does not display the Definition or the Gene Products Information To view these click on the display buttons under Definition and Gene Products Information The tables should unfold and the information should be displayed as shown in Figure 16 MacGO qoGet and GoView connection Mozilla e x File Edit View Go Bookmarks Tools Window Help Se Q a B http db math macalester edu GoProject connectjsp goview_call minus math macalester edu z s Search E T Reload amp hir iNe khia 22 Search Print m T AhHome wf Bookmarks 4 The Mozilla Organiza g Latest Builds ieee ba Ontologies Set 1 Set 2 Data Sources Evidence Types My Search All Search Within results Clear jr l Searc
17. of gene ACC All Definition Ontology Synonyms Gene Products information products sensu Mammalia Data Full Product Data Source ice gt Soure Name Symbol Synonyms information Evidence information 979295 paired Pax6 i i H e display display H gene 6 Evidence Name Comment inferred from genetic interaction inferred from mutant phenotype 1747 eye i display biological_pracess none hide 1 morphogenesis L oo What is Gene Ontology Copyright 2003 Macalester College Valid HTML 4 01 Valid CSS2 Figure 7 The types of evidence that tie pax6 to eye morphogenesis in mice A Similar type of search what can go wrong Another question you might have would be along these lines What membrane gene products in C elegans have unc in their symbol A possible way to set up this query is shown in Figure 8 The problem that you will run into is the prevalence of the word membrane in the definition and synonyms for terms in all of the ontologies As it is shown this query returns too many results The way to find what you are really looking for is to only choose to look for membrane in the name of the term Similarly the letters unc occur in far too many words in the full name and or synonyms of gene products in the GO database so you need to pick only the gene product symbol as shown in Fi
18. result should look like Figure 2 Notice that this results page has the English version of your query shown at the top MacGO goGet Mozilla Ontologies T ul Set 2 i Data Sources Evidence Types My Search Search Within results Clear E Return gene products in terms whose name partly contains triphosphatase in all ontologies in all data sources and in all evidence types Results _Click here to analyze results here to _Click here to analyze results results Pee O Name E A fa Products Ea gene 2 ee _Omoooy dae mirt Ea el toes 8 0xo 7 8 dihydroguanine hl _function toes activity rar a ae mea activity iT a S a e What is Gene Ontology Copyright 2003 Macalester College Valid HTML 4 01 Valid CSS2 3 ED w EJ Done a Figure 2 Results from a search for terms partially containing triphosphatase Notice that in the second column from the left are the list of terms from that search Each of these terms has a definition which you can see by choosing the display button in the Definition column That button is a toggle so that you can display and then hide the definition again To use database vernacular providing those display buttons are our way of letting you drill down to see more details about each term Notice on the far right we give you an indication of how many gene products are associated with each term If you choose to display those you get quite a bit
19. search click on the Search button on the top menu This should bring up the terms that have gene products with Pax6 in their symbol from the mouse genome database associated to them To find out what evidence type there is we will need to click on the display button under the gene products information and then again under evidence information The result is in Figure 7 from which we can see that the connection is inferred by both mutant phenotype and genetic interaction evidence To find out more details about each of the types of evidence please see http www geneontology org GO evidence html The evidence codes are another choice of filter that you have and it works like the data sources MacGO goGet and GoView connection Mozilla 5x X Eile Edit View Go Bookmarks Tools Window Help 4 3 B iM yx 5 http db math macalester edu GoProject connectjsp goview_call minus math macalester edu Search X Back Reload e i e 2 Print Im E Ah Home wf Bookmarks gThe Mozilla Organiza g Latest Builds Ontologies Set 1 Set 2 Data Sources Evidence Types My Search l Search Within results Clear 24 Retum gene products whose symbol partly contains pax6 in terms whose name partly contains eye morphogenesis in all ontologies in MGI data source and in all evidence types Results Click here to analyze results Term Name i Tem ik A
20. 2 il ax s Done S E Figure 17 Search results after narrowing by database Now that we have narrowed down our gene products lets get a little more information about them Just to make sure that the gene products are only from rat genome click on the tab Gene Products information this should collapse and display a table with information on the gene products From here click on the display tabs in the column labeled Data Source information and they should all display a rat genome database websitet URL Click on the three display boxes under Product Synonyms Data Source Information and Evidence Information in the row of the first gene product This will bring up more specific information including synonyms the type of evidence that links this gene product to the term and a link to a website with more information Figure 18 shows the data source information displayed for the first gene As of now the URL http rgd mew edu contains only rat genome database 25 M MacGO qoGet and GoView connection Mozilla x Elle Edit View Go Bookmarks Tools Window Help lt Ae A i a X 2 7 Aa B http db math macalester edu GoProject connectjsp goview_call minus math macalesteredu v s2 Search s X Back Reload Print T Home wf Bookmarks gThe Mozilla Organiza g Latest Builds Ontologies Set 1 Set 2 Data Source
21. GoView and GoGet User Manual Macalester College GO Exploration Tool Project goproject macalester edu Professor Libby Shoop Mathematics and Computer Science Department Contents 1 0 Introduction 2 1 1 GoView 3 1 2 GoGet 3 2 0 Installation 4 3 0 Tutorial 4 4 0 Reference 31 4 1 Exploring in GoView 31 4 2 Searching in GoGet 33 5 0 How to contact us and Acknowledgments 40 6 0 Bibliography 40 1 0 Introduction PLEASE NOTE Some of the examples in this manual were made from the May 2004 version of the GO database When you try the tools with a later version of the database things will look different because some of the term names and the structure of the ontologies will have changed The general way that the tools work has not changed GoGet and GoView are two new tools built as part of an extensible web application
22. H ATPase OSA1 none displ displ adenosinetriphosphatase dsp _display _tisplay 4002 adenosinetriphosphatase function 19667 Sarcoplasmictendoptasmic atA1_HUMAN oispry _cispiy ay 1 A full results table Egg T E Term Information ACC Accession number of the term in the database Term Name Full name of the term Definition A brief definition of the term Term Synonyms Other names for this term Gene Products Information Data Source ID ID number of the data source Full Name The full name of the gene product Symbol Symbol of this gene product Product Synonyms Other names for this product These categories will always be listed along with the Term information if you searched by terms or along with the gene products if you searched by gene products Ontology Function process or component Gene Products Terms Information More specific information on the genes and gene products involved in this process function or component or more Information about the terms associated with this gene product of gene products of Terms The number of gene products in the database for this Component Process or Function or the number of terms associated with this gene product This information will always be listed with the terms associated with a gene product or with the gene products of that term 38 Data Source Information The name of the database this product came from comments and a link t
23. again will make them all checked Suppose you want just the gene products from Flybase Pick that data source and choose Within results in this case it also works to choose Search again This should return 1 gene product from 1 term for the version of GO from May 2004 If you want to go back and expand the search you can add data sources but then you should choose Search instead If you had chosen more data sources that produced more results you could then refine your search by executing Within results again You can also try some other was to narrow your search For example go back to All choices pick All data sources and then in the Set 1 box labeled with a 1 in Figure 5 choose Full Name under Gene Product and type in NTP in the box It should look like Figure 5 Choose Search This will return fewer terms and fewer gene products this time only those gene products that contain NTP in their full name Notice this happens because the radio button labeled And is the default This means that you want gene products with NTP in their full name and are associated with terms that have triphosphatase in their name Choosing Or or But Not will have different results be careful For example if you choose But Not you will get all terms and their associated gene products that contain triphosphatase in their term names but not any gene products that
24. ame partly contains DNA binding in all ontologies in all data sources and in all evidence types Results _Glick here to analyze results here to _Glick here to analyze results results Term Name All Definition omoooy onttoay foies Gene Products information 7 DNA Hona ear ee nae Le _ SSE ee damaged _ display ies aha Oooo wy a others _ display ed HE pees _display a T _display i singles andad E a eae binding Product Source Smet o sme pie urce sourco cn eee Bem protein A 32 Peara HUMAN a protein A 70 HUMAN ml ee protein A 14 HUMAN lan kaier subunit epy play eee DNA pee _TREPA la HIES pee recF display Fal a kE ane and aT _CHLTR HAES ane recF DNA replication and me ECOLI Figure 10 Result for DNA binding terms with each associated gene product that contains the word replication in its full name The order of the first two fields in set 1 is significant in terms of what the resulting output looks like Because the first member of both set 1 and set 2 is a term the but not between the two sets pertains to gene products This means any gene products returned by set 2 are removed from set 1 So if a gene product is associated to a term that contains DNA replication it would be removed BEWARE If we had chosen to switch DNA binding and repair in set 1 and DNA binding and replication in set 2 listing the ge
25. and repair gene products in the set 1 box As of the May 2004 version 15 of GO this returns 5 terms with 1204 total gene product associations Then do a second search of DNA binding terms and replication gene products within those terms again using the set 1 box This returns 4 terms with 887 gene products The result of doing the but not a minus of the replication gene products from the repair gene products returns 5 terms with 1067 gene products Also the choice of using just the word repair and just the word replication as opposed to DNA repair and DNA replication are important The reason is illustrated in Figure 10 which shows the results of finding DNA binding terms with associated gene products whose name contains replication Note that the full name of some of the gene products contains the phrase DNA replication and repair protein If we had chosen DNA repair for our first set the text search index that we have set up in our Oracle database would not have found these gene products Similarly there are some named DNA repair and replication protein which also would not be returned if we had chosen DNA replication in set 2 as opposed to replication MacGO goGet Mozilla Ontologies TE ul set2 Data Sources Evidence Types My Search __ Al Search Within results Clear E Return gene products whose full name partly contains replication in terms whose n
26. atches and the very next character is a space to break to the next word You also have the choice of what information about a term you want to search its name its definition or any of its synonyms Typically it is best to start with its name and use the others if you are unsuccessful Important Searching Tips When choosing to return a set of terms you need to carefully consider choosing to search through name definition and synonyms all at once by selecting all three The definitions can be long and contain many words so they might get you off track For example the phrase catalyzes the reaction appears many many times in various term definitions so using catalyze in a search where you chose definition would return too many results The synonyms however might be very useful for terms that might likely have other common names that you are familiar with For example the term called 8 oxo 7 8 dihydroguanine triphosphatase activity has a synonym 8 oxo GTPase Beware Sometimes the text index on the names does not work as you might expect For the preceding example choosing to search contains partially for 8 oxo should return the 8 oxo 7 8 dihydroguanine triphosphatase activity but it currently does not We are working on making this work properly by switching to a new version of the database Oracle 9i will replace Oracle 8i in our implementation eventually and the text indices will improve As a
27. d results Most notably if the result should return nothing you might find that it tells you that the result is too large instead We are working on repairing this anomaly 3 2 Example 2 Another search using filtering Click on the ALF button on the top Menu This will bring up all of the search options again Suppose we wish to find out what type of evidence there is that connects the gene product Pax6 to eye morphogenesis in mice We want to search all three ontologies so make sure that the boxes to the left under the bold heading Ontologies are checked Click on the Term radio box on the top of set 1 Tf you hadn t caught this this button works like a start over button or a refine button to enable you to try again 11 Next click on the Name box on the left This will now let us type in our query In the text field eye morphogenesis It is the default but check to see if the and button is selected under this text field if it not select it Click on the Gene Product radio box above the second text field and the check the Symbol box In this next text field type Pax6 In this case Pax6 is the symbol for the gene as opposed to its full name Be sure the Full Name and Synonym boxes are unchecked If you type in Pax 6 with a space you will get no results The search is not caps sensitive so typing pax6 will return the same results For now we will do a simple search so we can lea
28. dence Types My Search A T Search Within results Clear A Return gene products in terms whose name partly contains triphosphata Please check the desired terms from the results and a Source Resu Search terms which have Mouse Genome Informatics but not FlyBase gene roducts associated with it from the set al Name f terms 8 oxo 7 8 dihydroguanine ad face ean eM Definition triphosphatase activity _ Ae v H Fea Sources oxo 7 8 dihydroguanine TIGR_CMR The None TIGR_CMR The Epeen tiphosphaiase aciviy ___ Institute for Genomic ang Institute for Genomic Research Comprehensive Research Comprehensive 47710 v Bieter eatenney etioeptatans display Microbial Resource Or Microbial Resource H RGD Rat Genome But RGD Rat Genome 17111 V nucleoside triphosphatase ataba sy atabase a E eee GeneDB_Tbrucei GeneDB_Tbrucei GeneDB_Thbrucei GeneDB_Tbrucei E Click nere to ar here to Click nere to ar l J7 thiamin triphosphatase activity a WB WormBase WB WormBase ___ database of nematode _ database of nematode thymidine triphosphatase activity dapiy biology biology nt os Mouse Genome c pas Mouse Genome gt triphosphatase activity informatics informatics ity conan amorstans C GeneD8 Gnorstns GeneDB_Gmorsitans GeneDB_Gmorsitans ZFIN The Zebrafish ZFIN The Zebrafish gy Information Network Information Network SS2 GeneDB_Lmajor
29. display emda ncaa eae eo ees a ee T v hemicellulose network display cellular_component none V hyphal cell wall display ee F itegrltcextrnalmamtrane sensu display cellular ssa cael none lignin network comar component none tok tL aea e a earna a a S l i PELEERE L ax EL w Es Done lt Pp Figure 23 GoGet popup window to send terms back to GoView AAA Graph Name Term Name extracellular Casparian strip a external encapsulating structure Casparian strip external encapsulating structure bud scar external encapsulating structure cell wall sensu Gram negative Bacteria external encapsulating structure cell wall sensu Gram positive Bacteria extracellular cellulose microfibril i external encapsulating structure cellulose microfibril external encapsulating structure chitosan layer of spore wall F Close Clear Figure 24 GoView s graph list window that pops up when you send terms to it from GoGet Minimize the GoGet application or move it out of the way and look at the GoView popup list shown in Figure 24 Notice that the top line shows that the Casparian strip term is also in a graph called extracellular Pick that by clicking once on it in the list GoView will take a few seconds to draw the new graph in a new tab and center the graph at the Casparian strip node Notice that other terms
30. e products associated with them OR choice You may also ask simply for those terms with mouse gene products associated to them by choosing the None choice the right hand column is ignored Note that to do any of these you have to start your initial query for triphosphatase terms again The second analysis tool finding gene products that are shared by a set of terms is currently under development 19 3 6 Starting your exploration in GoView Now we will show you how to use the GoView tool If you want to just explore around a bit and see what kinds of terms are in each ontology and see what the graphs look like this is the place to start Start out by opening up GoView In Section 2 we provide download information GoView looks like Figure 13 when it opens You will need to do this once Choose Properties from the Edit menu located in the menu bar at the top of the tool The only property you need to set is which browser you will use with GoView to display additional information If you are on a Mac you can use the Select button and choose your browser The GoGet tool displays best in the Firefox or Mozilla browser but works pretty well in Safari on Mac OS 10 3 On Windows Mozilla is again better than Internet Explorer On linux Mozilla is also the best choice and you will need to type in the path to your Mozilla executable You must choose a browser this way in GoView otherwise the following tutorial will not wo
31. ecause any child could have more than one parent The paths through the graph are directed because when you explore the graph you think about going from the top root and traveling down through each subcategory The graphs are acyclic because there is not a path from a child cycling back to any of its ancestors GI inferred from genetic interaction Set to Return The box indicated by 2 in Figure 1 enables you to choose which set of terms or associated gene products you would like to have returned The terms may have gene products from various species associated with them For example the molecular function term called nucleoside triphosphatase activity has one gene product from the Mouse Genome Informatics database associated with it whose full name in that database is nucleotriphosphatase and whose gene symbol is Ntp In GoGet we refer to the box indicated by 2 in Figure 1 as the Set 1 box If you choose Term as shown in Figure 1 then what will be returned to you is GO terms along with information about which gene products are associated with those terms Exactly which terms are returned depends on whether you choose Contains partially or Contains exactly The example startup query shown will return any terms that contain the phrase triphosphatase anywhere in it either in a larger word or as its own word The Contains exactly choice will usually return a smaller set of terms where the exact phrase m
32. ent sections where you can indicate what you would like to search for Ontology Choice The box indicated by 1 in Figure 1 let s you choose one of the three GO ontologies The GO database has defined terms in three different ontologies An ontology is a classification system for knowledge about a domain In this case the GO consortium members have developed three different ways to classify genes which are defined in GO2001 as follows Briefly molecular function describes what a gene product does at the biochemical level Biological process describes a broad biological objective Cellular component describes the Data Sources RGD Rat Genome Database GeneDB_Tbrucei GeneDB_Tbrucei WB WormBase database of nematode biology MGI Mouse Genome Informatics GeneDB_Gmorsitans GeneDB_Gmorsitans ZFIN The Zebrafish Information Network GeneDB_Lmajor GeneDB_Lmajor DDB DictyBase FB FlyBase lt lt lt 1 lt 7 lt 1 lt 1 lt 1 lt 1 lt 1 rains V TAIR The Arabidopsis Information Resource V UniProt The Universal Protein Knowledgebase TIGR Gene Index SGD Saccharomyces Genome Database GeneDB_Spombe GeneDB_Spombe K Ka V All Jv TIGR_CMR The Institute for Genomic Ri Comprehensive Microbial Resource GR Gramene A Comparative Mapping Resource for v TIGR_TGI The Institute for Genomic Research Evidence Types My Search All Search Clear 2 Evidence Types V Al
33. expression JV GeneDB_Lmajor GeneDB_Lmajor IMP inferred from mutant V DDB DictyBase a at i er v FB FlyBase v IC inferred by curator and Or But Not Term Gene Product F Full Name jv an Gramene A Comparative Mapping Resource for V NAS non traceable author Emam Cortana Pest rains statement igen e ee Jv TAIR The Arabidopsis Information Resource 7 IPI inferred from physical SETI EL J UniProt The Universal Protein Knowledgebase ae i And Or ButNot TIGR_TGI The Institute for Genomic Research V ND no biological data available e T TIGR Gene Index v IGI inferred from genetic interaction Term Gene Product V SGD Saccharomyces Genome Database a V GeneDB_Spombe GeneDB_Spombe Name Definition Contains Partially J Synonym Contains Exactly amp and Or But Not Term Gene Product Full Name Symbol a Contains Partially Synonym Contains Exactly ae Eb w Es G4 Done map Return gene products in terms whose name partly contains tziphosphatase in all ontologies in all data sources and in all evidence types Figure 4 Bringing the search criteria back up You can refine your search to only show gene products from certain data sources Click the All checkbox under data sources and all of the data sources become unchecked this too is a toggle so clicking it
34. g the X in the tab of the graph to the left of the graph s name Click on the cellular component ontology on the left and then on ce l then on external encapsulating structure to bring up the graph Figure 20 Each time you choose an ontology a subgraph list like cell or a graph itself you have to way a few seconds for the tool to find the next level list or the graph itself and display it Some information about the status is shown in read print above the place where the graph will eventually be displayed You do not have to download it again if you have saved it File Edit View Done Pick a new graph or explor Molecular Functions Biological Processes cell Cellular Component cellular_cornponent unknown extracellular immunoglobulin complex obsolete cellular component unlocalized e this one external encapsulating structure immature spore intracellular membrane midbody Close Graph lt OUT zoom Bar Nee View selected Terms in goGet external encapsulating structure glycocalyx capsule capsule sensu Bacteria capsule sensu Fungi extracellular matrix sensu Magnoliophyta cell wall I wall sensu Magnoliophyta cell wall sensu Fungi cell wall sensu Bacteria H
35. ganized as ontologies which are a diagrammatic and notational tool for describing knowledge about a domain Gruber93 Gruber95 The consortium has built and continues to revise three ontologies molecular function biological process and cellular component These are defined in GO2001 Briefly molecular function describes what a gene product does at the biochemical level Biological process describes a broad biological objective Cellular component describes the location of a gene product within cellular structures and within macromolecular complexes In addition to developing the ontologies the consortium members are assigning gene products from 26 model organism and sequence databases to one or more of the terms in each ontology The assignment is based on a particular kind of evidence including inference by direct assay by sequence similarity or by traceable author statement to name a few The gene products can be associated to more than one term in all three ontologies More information about the Gene Ontology Databases is available at the Gene Ontology Consortium s website www geneontology org 1 1 GoView GoView is used to illustrate the Gene Ontology Database graphically though graphs of different subsections of the three different ontologies It is navigated by selecting parts of the graph and observing the structure of portions of the ontologies The terms found in GoView can then be directly accessed in GoGet for more
36. gi hyphal cell wall innerlayer of spore wall spore wall sensu Fungi yeast frm cell wall chitosan laaro apor o O ef aval gensu Gram positive dityosine layer ofs pore Bacteria wall lt OUT Zoom Bar IN gt i me ell wall sensu Gram negative View selected Terms in goGet Meore J cell wal Cansu arama egati l cell wall sensu Bacteria Figure 22 Choosing multiple nodes in GoView Now that you have selected those nodes click View selected Terms in GoGet The GoGet browser window will display all of the terms and their gene products in a few seconds We now have a big list of terms in GoGet You can browse them in GoGet and see what gene products are associated with those terms Re analysis example The terms on this graph might be in other cellular component graphs This is a byproduct of the way we have to spilt each very large ontology into smaller subgraphs We can see what other graphs these terms are in by sending them back to GoView and getting a list of all graphs those terms are in In GoGet select all of the terms by checking the all box above the column of term names Bring up the analysis tool menu again in GoGet by clicking the Click here to analyze results button The result is shown in Figure 23 This time click on GoView Application Connection A popup window will come up and give you an English version of what you are asking to be sent back to GoView Hit the search butto
37. gure 8 MacGO goGet Mozilla 13 E Ontologies TE l Set 2 Data Sources Evidence Types My Search a Search Within results Clear A Ontologies V Molecular Function regan amao pasthy v Bological Process v Cellular Component Term Gene Product v Name membrane Definition amp Contains Partially vj Synonym Contains Exactly Term Gene Product Full Name junc Jv Symbol Contains Partially J Synonym Contains Exactly and Or ButNot Term Gene Product Name Definition Contains Partially J Synonym Contains Exactly amp and Or But Not Term Gene Product Full Name J Symbol Contains Partially a Synonym e Contains Exactly Done 2 D CZ Figure 8 Data Sources all TIGR_CMR The Institute for Genomic Research Comprehensive Microbial Resource RGD Rat Genome Database GeneDB_Tbrucei GeneDB_Tbrucei V WB WormBase database of nematode biology MGI Mouse Genome Informatics GeneDB_Gmorsitans GeneDB_Gmorsitans ZFIN The Zebrafish Information Network GeneDB_Lmajor GeneDB_Lmajor DDB DictyBase FB FlyBase 5 GR Gramene A Comparative Mapping Resource for Grains m TAIR The Arabidopsis Information Resource 7 UniProt The Universal Protein Knowledgebase TIGR_TGI The Institute for Genomic Research index TIGR Gene SGD Saccharom
38. h from GoView Results Click here to analyze results Tem of Acc Name Definition Ontology lg Tom Gene Products information gene Ma ynony products 1558 biological_process none hide Ee regulation any process that ofc ee ies the Data Product PAA Evidence rowth Source Full Name Symbol Source e g freaueney i a a ID Synonyms formation formation pesa rene BC4V1_OCO012_07582 rere display CE 23804 rene JC1 1_oc0002_03571 rene TF E 35055 Cak4 Cdk4 display display display 43901 foxo foxo display display display 44380 gig gig display display display i dag l E g Mer display display display esr s0 Fas85D Ea display display js fet Tet display display display 66476 Cholinephosphotransferase 1 homolog 8C025 display display display 66477 Cholinephosphotransferase 1 beta QSNRGB none display display 67326 CYR61 protein precursor CYR6_MOUSE display display display iy X EZAC a i i i ag Figure 16 Definition and Gene Products Information As we can see from the of gene products column regulation of cell growth has 504 gene products From here we can narrow our result to be specific to one or more organism Choose the Set 1
39. information about their gene products 1 2 GoGet GoGet searches for terms and gene products using a number of search criteria It then returns the Term Name Definition Ontology Term Synonyms Gene Products Information and of gene products for the term s found in the search It also gives links to the original databases web page for more information about specific gene products 2 0 Getting the Programs To get the GoView and GoGet software go to http db math macalester edu goproject To use GoGet click on the link on the left labeled Search the Gene Ontology with GoGet To get GoView click on the link labeled Explore the Gene Ontology with GoView This will download an executable Java application which should start up if you have Java installed on your computer So if you have a Macintosh this will work without doing anything If you have a Windows or linux machine and have not installed the Java Runtime Environment JRE we have a link for you to use to install it It is a relatively easy procedure 3 0 Tutorial In this section of the manual we will walk through several examples of how to use GoGet and GoView We will start with the querying capabilities of GoGet and then show the ways to explore the ontologies using GoView Lastly we will show how the two tools can be used together 3 1 Example 1 Simple Searches in GoGet From http db math macalester edu click the Search the Gene Ontology with GoGet
40. k the name box and type in triphosphatase in the text field Click Search Select all of the terms returned by the search for analysis by checking the all box under term name Bring up the analysis tool menu again by clicking the Click here to analyze results button Your browser application should look like Figure 11 17 M MacGO goGet Mozilla Build ID 2003021212 Hl File Edit View Go Bookmarks Tools Window Help Debug QA 2 T 2 v A a amp http db coath cnacalester edu GoProjectgoGet5 jsp ViewSubmit Search amp ontology_checkb x asua S 5 rint Back Reload Ah Hore uf Bookmarks ff Red Hat Network L Trining sexpert P Soine P First GP Developers S Erbeddea Pah GP Documentation L Downloads Ontologies Set 1 Set 2 Data Sources Evidence Types My Search all Search Within results Clear Return gene products in terms whose name partly contains triphosphatase im all ontologies in a sources and in all evidence types Results a Click here to analyze results coo Name Gene Products Gene Products Shared by Terms a a RNA dependent adenosinetriphosphatase no display display What is Gene Ontology Copyright 2003 Macalester College Valid HTML 4 01 Valid CSS2 Figure 11 Results before analysis This time click the Gene Products Specific by Terms button You will get a screen like Figure 12 18 MacGO goGet Mozilla Ontologies TE ul set2 Data Sources Evi
41. k will have more subgraphs Once a graph is selected it will appear in the large window and on the left in the context graph To close the graph click on the Close Graph button on the right More than one graph may be open at a time to open additional graphs repeat the above process To switch between open graphs click on the tabs above the graphs To move to a specific place in the graph click where you would like to be centered on the context graph on the left To scroll on the graph use the scroll bars on the larger graph To zoom in or out on the large graph drag the Zoom Bar in the lower right corner or hit the IN gt or lt OUT buttons to zoom in or out 4 1 2 Getting more information in GoGet To find more information on a component highlight it in red by clicking on it To select multiple nodes at once click and drag a box completely around the desired nodes This can be done on the large graph or the small graph on the left Once you have selected the term s you want click View Selected Terms in GoGet in the lower left corner This will open up GoGet in an Internet browser if it is not already open GoGet will come up with all the same information about that term as it would have if you searched for it with GoGet 33 4 2 Searching in GoGet To open GoGet without looking for a specific term from GoView go to the view menu in GoView and click open goGet In GoGet there will be 8 buttons along the top of the screen with the f
42. l v TAS traceable author statement V IEA inferred from electronic annotation NR not recorded ISS inferred from sequence or structural similarity IDA inferred from direct assay IEP inferred from expression pattern IMP inferred from mutant phenotype lt 1 lt lt I lt lt v C inferred by curator NAS non traceable author statement Pl inferred from physical interaction ND no biological data available lt lt 4 v gig Return gene products in terms whose name partly contains triphosphatase in all ontologies in all data sources and in all evidence types What is Gene Onto Copyright 2003 Macalester College Valid HTML 4 01 Valid D A Initial State of the GoGet search tool when you first access it location of a gene product within cellular structures and within macromolecular complexes Terminology Aside Each ontology is a graph structure with a root that is the starting point From the root term each term below it is a subcategory For example some of the subcategories under molecular function are antioxidant activity binding catalytic activity and transporter activity Each of the subcategories may be broken down into additional subcategories In graph terminology the subcategories of a term are called the child terms and the category above the child is called the parent The GO ontologies are graphs b
43. n in that popup window Figure 23 In a moment this will bring up a little window of the GoView application with the names of all of these terms on the right and the graph that each is in on the left Figure 24 30 A 00 MacGO goGet and GoView connection Mozilla gt a 2i amp z Hi 4 http db math macalester edu GoProject connect jsp goview_call geol73 geol m v Search v m 2 Back Forward Reload Stop Print i Ah Home H Bookmarks L Lester Log In Page Ontologies Set 1 set2 Data Sources Evidence Types My Search i Search Within results Clear 2 Search from GoView Please check the desired terms from the results Show the graphs of the set of terms 7 Casparian strip bud scar cell wall i sensu Gram negative Bacteria cell wall Term Name sensu Gram positive Bacteria cellulose 4 I gt All D v icrofibril chitosan layer of spore v v Casparian strip of gene products Close Search v bud scar display cellular_component none display 3 v cell wall sensu Gram negative Bacteria display cellular lt componentl display v cell wall sensu Gram positive Bacteria display cellular component splay G E A T e v cellulose microfibril display cellular_component none i 8 a A N x a Ld 8 5631 l v chitosan layer of spore wall display e ee display i V dityrosine layer of spore wall
44. n Novartis Found Symposium volume 247 pages 66 80 Gruber T R 1993 A translation approach to portable ontology specifications Knowledge Acquisition 5 2 199 220 Gruber T R 1995 Toward principles for the design of ontologies used for knowledge sharing International Journal of Human Computer Studies 43 5 6 907 928 The Gene Ontology Consortium 2001 Creating the gene ontology resource design and implementation Genome Res 11 8 1425 33
45. n alternative to searching for terms you can also to search for particular gene products This will return the gene products that match your text search and the terms that they are associated with If you choose one or two of the ontologies fewer results will be returned because gene products associated with terms that are in an ontology that you left out will be removed from the results You may need to do this kind of filtering if you are searching using words that might be quite prevalent in the names of gene products This happens because there are only so many results that can be displayed in a web page without breaking the browser so we have to check for the number of results coming back and refuse to display them if there are too many You can combine a term and gene product search together we will show examples of this later First you can get a sense for what is returned from a search by simply using the defaults that appear when the tool comes up In Figure 1 notice the area of the tool indicated with a 6 This is an English version of the query that you are formulating This is there to help you envision what will be returned using your choices Read it and make sure that it seems to make sense to you we will explain data sources and evidence types in a while Click on the button labeled Search near the upper right corner When you do subsequent searches it also works to hit return when your cursor is in the text box The
46. n the mouse is over it We did this to enable complete visualization of the longer terms but it might take some getting used to File Edit View 21 _cell growth Molecular Functions Biological Processes Cellular Component Done Pick a new graph or explore this one cell activation a cell death 7 cell growth and or maintenance cell motility cellular defense response cellular response to starvation ZZ cell communication cell differentiation cellular physiological process membrane fusion regulation of cellular process behavior biological_process unknown cellular process development obsolete biological process physiological process regulation of biological process emt ti L Pa eee TES ix autophagy a budding z cell growth 4 cell homeostasis Z cell organization and biogenesi cell proliferation S GET WA Close Graph cell expansion cell wall modification during cell expansion cell elongation ie SNN _ oocyte growth metabolism resulting in cell growth cell growth interpretation of nuclear cyoplasmic ratio regulation of cell growth Insecta oocyte growth sensu SSS WN SSSSSS growth interpretation of nuclear cyto ratio to regulate cell SSS
47. ne A Comparative Mapping Resource for Grains annotation Tem C Gene Product lv fo FlyBase m ENA not recorded 7 Name __ trishosphatase Jv mai Mouse Genome Informatics J 188 inferred from sequence or i structural similarity J Definition Contains Partially Jy wh WormBase 7 IDA inferred from direct assay Synonym Contains Exactly m tairy The Arabidopsis Information Resource gt IEP inferred from expression pattern and C or But Not JY tigr_atht y The Institute for Genomic Research Arabidopsis gt IMP inferred from mutant phenotype C e thaliana database A ms Term Gene Product lv tigr_cmr The Institute for Genomic Research m C inferred by curator 7 Full Name Comprehensive Microbial Resource Jv NAS non traceable author statement E Symbol o i j lv pompep Schizosaccharomyces pompbe protein data m IPI inferred from physical interation Contains Partially Synonym C it 7 rgd Rat Genome Database ND no biological data available Contains Exactly gi j te TrEMBL v IGI inferred from genetic interation m tgi The Institute for Genomic Research TIGR Gene Index Iv sgd Saccharomyces Genome Database and or But Not Term Gene Product Name Definition Contains Partially Return gene products in terms whose name partly contains triphosphatase M Synonym C Contains Exactly in all ontologies in all data sources and in all evidence types
48. ne product first the but not would have been sensitive to terms This means terms that had DNA replication genes would have removed from the set 1 terms This is most likely not what you would want from a query like this one 16 The only change we could have made that would still return the same results are excluding DNA binding from the second Having DNA binding in the second set is unnecessary but it is left in because the but not operation is slow and narrowing the field that is being subtracted will speed it up 3 4 Example 4 Searching Within Results Once you have a set of results you can search within those to refine your results further For example after you have obtained the results from the query in the previous section you could try finding only the gene products that contain the word excision by using the Set 1 box and clearing out the Set 2 box do this by unchecking all choices in Set 2 3 5 Example 5 Another Analysis Tool Gene Products Specific to Terms by Species In certain situations you may want to know whether one species has a particular function that another does not or whether two species share a function or functions We have created some special analysis features to help you ask these questions Let s walk through an example using the molecular function terms that contain the word triphosphatase Start by pressing clear to start a new search Select terms in the top of set 1 chec
49. o the databases specific information on this gene product Evidence information which of the twelve evidence types this information was gotten from Some parts of the table will not be listed and you will need to click the display button in the corresponding space to view them To hide this information click the hide button in the same space 4 2 9 Analysis To analyze the gene products click the click here to analyze results button To hide the analysis tools click the click here to analyze results button again The click here to analyze results button will bring three options Gene Products Specific to Terms Gene Products Shared by Terms and GoView Application Connection To use any of these tools you will need to select one or more terms to analyze If you got your terms through a search by terms or through GoView click on the check boxes to the left of the terms If you got your results by searching for a gene product you will need to click on the display button under Terms Information to bring up the check boxes for the terms Gene Products Specific to Terms This will narrow the gene products by which database they came from Select which term s gene products to look for Choose one or two databases and specify if you want to see the products that are in one both either neither or one but not the other Once you have selected the database s click search in to find the gene products Terms that have no products in the sea
50. of extra information about each gene product including a link back to its original data source For example try choosing to display the gene products information for the third term down from your result then choose to display the data source information for the first gene product Notice that the table increases in size width and height as you drill down The result should look like Figure 3 MacGO goGet Mozilla Ontologie ul Set 2 Data Sources Evidence Types My Search Search Within results Clear E ll ontologies in all data sources and in all evidence types rsults rsults Gene Products information display Evidei informe 29 g5 Hi 7 E S 8 i 47718 NTPase mt Tena Pe METJA NTRAMA S cal display dept s _ a at 8 z 7 o ae Eb w Es G amp Done H F Figure 3 Result of drilling down to obtain more information about gene products associated to a term If you click the link under URL you will get a new window to the original database for this gene product Notice that FlyBase the home of Drosophila melanogaster data calls this gene NTPase and other databases have named the gene product Nucleoside triphosphatase and some don t even have a name yet This is why the GO consortium got together to try to place these gene products together in one category in this case based on their molecular function
51. ollowing functions Ontologies Set 1 Set 2 Data Sources Evidence Types My Search All Search Within results Clear Ontologies Show Hide Ontology search criteria Set 1 Show Hide Set 1 Set 2 Show Hide Set 2 Data Sources Show Hide Data Source search criteria Evidence Types Show Hide Evidence Type search criteria My Search Show Hide English summery of search All Show Hide all search options Search Begin search Within Results Begin search of of results Clear Reset and clear the search fields and select all Ontologies Data Sources and Evidence Types To begin a search click on the All button if the search criteria are not already on the screen The starting point of GoGet is seen in Figure 25 M MacGO goGet Mozilla Build ID 2003021212 z File Edit View Go Bookmarks Tools Window Help Debug QA 2 X D r a 3 amp http vdb oath macalester edu GoProjectigoGet5 jsp a Search s X acl eloa rint Al 4b Home ub Bookmarks L Red Hat Network L Training L Support L Software L Hardware L Developers L Embedded L Search L Documentation L Downloads Ontologies Data Sources Evidence Types My Search Search Clear Ontologies Data Sources Evidence Types Molecular Function Jy all Jy all Bological Process m sp Swiss Prot protein database v TAS traceable author statement Cellular Component 7 ensembl Database of automatically annotated genomic data V IEA inferred from electronic Jv gr Grame
52. pattern J Synonym Contains Exactly a V ZFIN The Zebrafish Information Network v GaneDG_Lmajor GeneD8_Lmajor V IMP inferred from mutant r e V DDB DictyBase phenotype Term Gene Product V FB FlyBase V IC inferred by curator And Or But Not v Full Name NTP v G Gramene A Comparative Mapping Resource for V NAS non traceable author Symbol Contains Partial rains statement 2 synonym e i ly V TAIR The Arabidopsis Information Resource Jv IPI inferred from physical 2 Contains Exaciy J UniProt The Universal Protein Knowledgebase Baan i And or But Not V TIGR_TGI The Institute for Genomic Research Jv ND no biological data available r T TIGR Gene Index V IGI inferred from genetic interaction Term Gene Product V SGD Saccharomyces Genome Database a Name v GeneDB_Spombe GeneDB_Spombe v T Defniton Contains Partiaty L aaau A J Synonym f Contains Exactly Return gene products whose full name partly contains NTP in e e e terms whose name partly contains triphosphatase in all And Or But Not ontologies in all data sources and in all evidence types Term Gene Product Full Name J Symbol Contains Partially 7 Synonym Contains Exactly 3 ED w Es G4 Done H F Figure 5 A refined search to return certain gene products Bug Warning There are some cases when searching within results will return od
53. rch will no longer be displayed To close without searching click cancel This will return results in the same fashion as a search by term name Gene Products Shared by Terms This will find out which products are shared by one or more term s This feature is currently under development Select which terms to check for shared products in Once the terms are selected click search to search To close without searching click cancel This search returns data the same way as if you searched by gene products To further analyze these results you can check the boxes of whatever terms you would like more information on and use the analysis tools on them 39 They will all start out being selected to change this you will need to press the details button to see their check boxes 4 2 10 GoView Application Connection This will center the GoView graph window on specific terms You needed to have started GoGet by launching the browser from GoView as described in section 3 Select which term s you would like to be able to center the GoView graph on Once the terms are selected click the search button This will open up a new popup window that is part of the GoView program It will be a list of the selected terms To cancel and not open this window click close To center the GoView graph on a term click on that term in the new popup window Terms will not be removed from this window until the program is closed More terms can be added
54. rk Each time you use GoView you will need to make sure the browser you have chosen using Edit Properties is not open and running GoView needs to start the browser itself in order to establish a connection between itself and the browser to send information back and forth File Edit View Choose an ontology Molecular Functions Cellular Component Biological Processes Figure 13 GoView at startup The GoView tool is a starting point for exploring the ontologies and their terms To use GoView you will need to start by selecting one of the three ontologies that you would like to explore For this tutorial we shall look at the following example What are the gene products that are associated with cell growth regulation in rats 20 To answer this question try the following e select Biological processes ontology from the list on the upper left hand corner of the screen This will open up a list of graphs of biological processes e Next select cellular processes in the next list The asterisk following cellular process just symbolizes that the graph is very large and so another list will open to show you the terms that are children of cellular process From the resulting list select cellular physiological processes and then from the next list select cell growth and maintenance and finally select cell growth from the last list So the overall sequence is Biological processes cell
55. s Evidence Types My Search All Search Within results Clear Search terms which have Rat Genome Database but not Mouse Genome Informatics gene products associated with it from the set of terms regulation of cell growth Results Click here to analyze results Tem ra Ontology i syromms Gene Products information 7 1558 ov display biological _process none hide regulation Dat f cell a J owth Full Name Symbol Binaan Data Source information He fr ide H 986280 cytokineinducibleSH2 containingprotein Cish display Database kas URL Rat httpvirgd mew edu query query cqi id RGD 69261 Genome Database 298805 neue Stegrowthactortinsingerotens pee display display eesee0 feteuinecostiesH2 contringerotos cions roro E pa enaner Igtop2 aispiay ce _ 007506 rsulinikegrowthfactor bindingproteing pe display display I 287507 insuiin ikeqrowthfactor bindingprateins lotpS aisn disnlaw se YO Se Figure 18 Gene product data source information displayed Now click on the link under the URL column This will open up the web page of the database this gene product is from Figure 19 NOTE these website links are fragile we try to keep up but sometimes they change and may not work 26
56. system based on Java 2 Enterprise Edition technology GoGet has a user interface that enables users to ask biologically interesting questions such as 1 What are the DNA binding proteins involved in DNA repair but not in DNA replication and 2 Of the terms containing the word triphosphatase which have associated gene products from mouse but not fruit fly Results of such queries can be viewed in a collapsed tabular format that eases the burden of getting through large tables of data GoView enables users to explore the large directed acyclic graph structure of the ontologies in the GO database The two tools are coordinated so that results from queries in GoGet can be visualized in GoView in the ontology in which they appear and explorations started from GoView can request details of gene product associations to appear in a result table in GoGet The goal of this project was to provide powerful new ways for biologists and biology students to explore the Gene Ontology GO data that is being developed by the GO consortium The GO Consortium was formed to build a common annotation to describe genes and their products in any organism Ashburner00 GO2001 Ashburner02 As stated in GO2001 one of the consortium s goals was to create a shared language of biology by compiling a comprehensive structured vocabulary of terms describing different elements of molecular biology that are shared among life forms The structured vocabularies are or
57. ted with terms that have DNA binding in the selected term fields Or will return all gene product term pairs that meet either criteria If your searched DNA binding in terms or DNA repair in gene products it will return all gene products that have DNA repair in the selected gene product fields with all terms associated with them and will also return all gene products that are associated with terms that have DNA binding in the selected term fields But not will return all the terms pairs meet the first criteria but do not meet the second So if you searched DNA binding in terms but not DNA repair in gene products it will return all terms that have DNA binding in the specified fields with their gene products but it will not include gene products that have DNA repair in specified fields 4 2 3 Using both sets Start by filling out both sets as if you were using them alone There are three queries options to choose for using both sets and or and but not These have the same names as the searches inside the sets but have different functions They are more general than their counterparts in the sets and have different functions depending on what is in set 1 What determines their function in what is selected in the top of set 1 term or gene product If the very top radio box is gene product than the search will be term sensitive This means if the and radio box is selected the pairs from the top will be compared to the terms from
58. the second box and any pairs from the first set that do not have one of those terms from the second set will be eliminated So the and is sensitive to the terms alone not the pairs But not works the same way Any pairs from the first set that have a term from the second box will be removed Or is different this will just combine the two list together removing any repeat pairs When the top radio box is term than the search will be sensitive to gene products This means if you use and it will look at the list of pairs from the first set and remove all pairs that do not have a gene product that is a member of the second list But not works the same way Any pair from the first set that has a gene product that is a member of the second set result will be removed Or will do the same thing it did before and combine the two lists not repeating pairs it is still sensitive to entire pairs not just gene products 4 2 4 Data Sources Select which of the databases to search Select one or more databases by clicking the check boxes to the left of the name of the database Select or deselect all databases by clicking the All check box You may wish to do this if you are searching for gene products in a specific organism For example if you are looking for gene products in drosophila you want to search Flybase fb 36 4 2 5 Evidence Select which of the 12 types of evidence types that will be allowed in the search Select one or more of the e
59. ular processes cellular physiological processes cell growth and maintenance cell growth This will bring up the graph of cell growth and its related terms There will be two graphs displayed a readable one on the right and a small one to the left called the context graph because it provides the overall context of what this graph looks like This context graph is especially useful for the larger graphs in GoView there are many you can try opening up other graphs if you d like they come up in separate tab windows in GoView We ve chosen this smaller graph to make it easier to show you how to pick terms and get more information about the gene producst in them NOTE The first time the graph is displayed the context view on the left may not appear Just resize your window a bit and it will show up We re trying to fix this problem You can move around the graph by using the scroll bars or by clicking on the context graph on the left where you would like to be centered You can also move the red box in the context graph and the readable graph on the right will move accordingly to match its location on the context graph Now going back to our example select the node term called regulation of cell growth on the readable graph by clicking on it and it should get highlighted in red as shown in the screen shot in Figure 14 Due to the size of some term names each list panel is programmed to become wider whe
60. ve the lower search box blank We only want to find genes in mice so we need to select fewer databases Click the all checkbox to unselect all the data sources and then click the mgi Mouse Genome Informatics box We want to search all evidence types because we are looking to see what type of evidence there is If the AU radio box under evidence is not checked click it W MacGO goGet Mozilla Build ID 2003021212 ca x 7 File Edit View Go Bookmarks Tools Window Help Deug QA 4 ies T 2 Le A a http db math macalester eduGoProject goGet5 j Search S4 X Im Back Forward Reload 4 piat IP 2 Print 4 Home af Bookmarks L Red Hat Network L Training L Support L Software L Hardware L Developers L Embedded L Search L Documentation L Downloads Ontologies Set 1 Set 2 Data Sources Evidence Types My Search All Search Clear Ontologies Data Sources Evidence Types Molecular Function a v al v Bological Process E sp Swiss Prot protein database v TAS traceable author statement 7 Cellular Component ensembl Database of automatically annotated genomic data V IEA inferred from electronic E gr Gramene 4 Comparative Mapping Resource for Grains annotation Term Gene Product fb FlyBase Jv NR not recorded Jv Name fye morphogenesis x mgi Mouse Genome Informatics m c Pe eade sequence or m RAA 2 Contains Partially x oie eee Jv DA inferred from direct assay nonym j aie 3 F
61. vidence types by clicking the check boxes to the left of the type of evidence Select or unselect all evidence types by clicking the All check box The data in the Gene Ontology Database is of variable reliable because of what types of evidence it is based on Depending on how confident you want to be in the information you can choose what types of evidence you want to accept For more information about the evidence types go to http www geneontology org doc GO evidence html 4 2 6 Search Once these fields are filled out click search along the top bar to begin the search If it does not begin to search one of the fields may not be complete If this is the case a box will pop up informing you that your search is incomplete check that you have written something in the text field This may also happen if you have not selected any ontologies data sources or evidence types If the search was successful results will be displayed and the search tools will be hidden If there were no results the search tools will remain open and a box will pop up that says no match found 4 2 7 Searching within results This button works the same as the search button but the search is done only on the results of the previous search and not on the entire database 4 2 8 Results Depending on what how the data in GoGet was searched for it will bring it up data in one of three ways If GoGet was brought up by a search of only terms or through GoView it
62. will have a list of terms and each term will have a list of associated gene products ACC ay easy MLET ec SAANS pae ae 8413 7 8 dihydro 8 oxoquanine triphosphatase none function none 4002 adenosinetriphosphatase hone function none o dipy 7111 T ructeosiae triphosphatase free function frre aw ft A term results table TUM If GoGet was brought up by a search of only gene products it will list the gene products and their information and then list the associated terms under each gene product with the term information 7 Terms information Data Source ID Ontology Product Synonyms Tall of Terms 67898 RNA triphosphatase CTL1 process display display 1 A gene products results table Ui If GoGet was brought up by a search of both gene products and terms it will have a separate column for each gene product term pair with all term and gene product information Term Name A Tem pan Product pas Evidence ACC all Defintion Synonyms Ontology Source Full Name Symbol Synonyms eoue information 8094 DNA dependent disptay__ funetion H ATPase Osat aa Ton adenosinetriphasphatase _tisply_ _display_ _tisplay 8094 i DNA dependent display function 70482 DNA dependent ATPase RAD26 display aaa eines adenosinetriphosphatase dispis human Cockayne _display ispay _ display syndrome B gene ERCC6 homolog 8186 RNA dependent none display function 46251
63. yces Genome Database E GamE craes GeneDB_Spombe Evidence Types V Al v TAS traceable author statement V IEA inferred from electronic annotation Jv NR not recorded Jv ISS inferred from sequence or structural similarity Jv IDA inferred from direct assay V IEP inferred from expression pattern V IMP inferred from mutant phenotype V IC inferred by curator Jv NAS non traceable author statement v IPI inferred from physical interaction V ND no biological data available V IGI inferred from genetic interaction Return gene products whose symbol partly contains unc in terms whose name definition or term synonym partly contains membrane in all ontologies in WB data source and in all evidence types synonym should not all be picked A A query that will return too many results name definition and 3 3 Example 3 A More Advanced Search in GoGet Now let s try a more complicated search In addition to using the Set 1 box that you have used in previous searches we will also use the second Set 2 box below it Notice that set 1 and set 2 have light blue backgrounds and a white background strip between them with a choice of And Or and But Not between set 1 and set 2 A way to distinguish these is to toggle the Set 2 button on and off and see the set 2 box disappear and reappear Lets find DNA binding proteins that are

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