Pathway Tools Release Note History

This document summarizes the release history of the Pathway Tools software. Version numbers not shown here were internal releases only.

Release Notes for Pathway Tools Software Version 12.0

Released on April 1, 2008

General Changes

• Macintosh port. We have ported Pathway Tools to the Macintosh. In this first version of the port, only the Navigator and Editors are supported. PathoLogic is not supported. We expect to add support for PathoLogic in a future version.

• New multi-platform installer. All Pathway Tools platforms now use the same new installation tool, allowing for a consistent installation approach on all platforms.

• Incorporation of genome annotation updates. A new tool supports the user in merging a new, external genome annotation into a PGDB. The tool can be useful for incorporating a new version of a genome annotation into a PGDB. The new annotation is supplied as a PathoLogic-format file. The annotation update tool detects all differences between gene and protein information in the supplied file and that in the PGDB, and presents those differences interactively. The user interactively controls which differences are incorporated into the PGDB, and which are rejected. After the annotation update is complete, PathoLogic can be executed to re-evaluate metabolic pathways. New pathways will be added to the PGDB if either (a) They are new to MetaCyc since the last time PathoLogic was run and have sufficient evidence, or (b) They were previously not predicted as present because of insufficient evidence, but now the presence of additional enzymes provides sufficient evidence, or (c) They were previously manually deleted from the PGDB but now have additional evidence because of the presence of additional enzymes. The user is shown all new pathways and given the opportunity to accept or reject them. This tool can be invoked through the PathoLogic command Build->Update Build for Revised Annotation, and is documented in Section 6.3.8 of the User's Guide.

• New tracks mechanism for ChIP-chip data. A new X-Y plot style of tracks for the Pathway Tools genome browser allows the user to visualize ChIP-chip datasets against the genome. ChIP-chip intensity measurements can be visually correlated with promoters, gene positions, and operon boundaries. For more information see Section 3.8.11 of the User's Guide.

• Attenuation. Pathway Tools has been extended to encode six mechanisms of attenuation. The Editors have been extended to support curation of these attenuation types, and each type is displayed appropriately on operon diagrams and on transcription unit pages.

• NCBI Taxonomy integrated into Pathway Tools. The NCBI Taxonomy DB is now integrated into all Pathway Tools versions that include the MetaCyc DB. This change was made for several reasons including allowing specification of the taxa in which MetaCyc pathways occur using NCBI Taxonomy, and allowing querying of MetaCyc pathways using NCBI Taxonomy.

• Modified GO term presentation. On protein pages and gene pages, the presentation of GO terms has been moved and restructured so that terms are sorted within the three domains of the Gene Ontology.

• Improved storage of sequences and overview graphs. This improvement is relevant only for PGDBs stored in a MySQL or Oracle relational DBMS. We have extended this PGDB storage mechanism so that the nucleic-acid sequence data and cellular overview data are now stored in the relational database. In the past, these data were stored in files that had to be manually replicated on the computer of every person accessing the PGDB in desktop mode. Now that replication is no longer required.

• New configuration parameters. A number of new configuration parameters have been added to ptools-local/ptools-init.dat. The file will be updated to contain the new parameters after you have run the new version of Pathway Tools. Check for new variables that may be relevant to your work. For example, if you operate a Pathway Tools based Web site, there is a new parameter that lets you enter the name of your Web site (e.g., "MouseCyc"), for use in messages and in Web pages generated by Pathway Tools.

• Highlight genes in Genome Overview. The Genome Overview now includes a command Overview->Highlight Genes by Substring, which will highlight in the diagram all genes whose name or synonyms contains a specified substring.

• New refresh command. The new command Tools->Pane->Refresh Panes will redraw the Navigator window in cases where it may have become corrupted.

• Improvements to metabolic map poster. The metabolic map poster than can be generated from a PGDB has undergone several improvements including the addition of pathway class labels to pathway groups, and improvements to the positioning of text.

• Web accounts system. The Pathway Tools Web server now includes a mechanism whereby users can create accounts through the Web. These accounts provide a way of registering the people who use a Pathway Tools operated Web site. Once an account is established, users can define preferences that control the appearance of Pathway Tools generated Web pages. The user accounts can also store configuration information such as organism lists used in the comparative genomics tools, and settings for the omics viewers. User accounts are stored in an external MySQL database. This facility is disabled within Pathway Tools Web servers unless you explicitly turn it on. For details, see Chapter 8 of the User's Guide.

• User access control. Using a facility separate from the Web accounts system, it is possible to limit the accessibility of some or all PGDBs within a Pathway Tools Web server to users who are authorized through a supplied file of usernames and passwords. For example, the Pathway Tools administrator could allow some PGDBs within their Web site to be available with no restriction, but limit access to other PGDBs to specified lists of users. For details, see the descriptions of the -passwd-file and -acl-file options in Section 2.3.1 (Command Line Arguments) of the Pathway Tools User's Guide.

• Advanced Query Page. The Advanced Query Page has undergone a number of improvements, bug fixes, and optimizations.

• Species Comparison on the Cellular Overview. The Cellular Overview Diagram available through the Web can be used to highlight reactions shared with other organisms.

• Genome Overview now available in web mode. When invoking the Web-based omics viewer, the user can specify that omics data should be displayed using the cellular overview, the genome overview, or both.

• Hyperlinkable Omics Displays. Omics Viewer displays are now accessible via the HTTP GET method, with the datafile specified as a URL or file on the server, which means that web developers can now generate hyperlinks that generates an omics display with a supplied omics datafile and set of parameters. For more information, see Section 2.4.5.1 of the User's Guide.

Changes to PathoLogic

Release Notes for Pathway Tools Software Version 11.5

Released on August 15, 2007

General Changes

• We have completed the first phase of an effort to endow Pathway Tools the capability to represent and manipulate information about a wide range of cellular regulation. In this first phase, we designed a new database schema for regulatory information, and we retrofited Pathway Tools existing mechanisms for manipulating information about the regulation of transcription initiation to work with this new and expanded regulatory schema. For example, Pathway Tools components for displaying and editing operons have been reworked to use the new regulatory scheme, as have tools for displaying and editing substrate-level regulation of enzyme activity. These changes required changes in the format of the Pathway Tools flat file dumps as described below.

  In more detail, the new representation is as follows. A new Regulation class has been created, with subclasses for substrate-level enzyme regulation and regulation of transcription initiation, as well as for several other forms of regulation. Each regulation frame forms a link between a regulator and a regulated entity (via the slots REGULATOR and REGULATED-ENTITY). The MODE slot specifies whether the regulatory effect is activatory or inhibitory.

  For enzyme modulation, the regulated entity will be an Enzymatic-Reaction frame. The MECHANISM slot of the Regulation frame specifies whether the modulation is allosteric, competitive, or any one of a number of other controlled vocabulary terms. These regulation frames replace the old ACTIVATORS-* and INHIBITORS-* slots (e.g. ACTIVATORS-ALLOSTERIC, INHIBITORS-COMPETITIVE, etc.), which are now deprecated.

  For regulation of transcription initiation, the regulated entity will typically be a promoter, and the regulator will be a transcription factor. The new slot ASSOCIATED-BINDING-SITE links to the binding-site for the transcription factor. This obviates the need for the binding-site/transcription-factor and promoter/RNA-polymerase complex frames that were part of the previous representation, as well as the DNA-binding-reactions that formed them, and all such complex and DNA-binding-reaction frames have been deleted. A new slot, BINDS-SIGMA-FACTOR, has been added to the Promoters class to indicate which sigma factor(s) are involved with transcription initiation at a given promoter. Since a given DNA binding site may regulate multiple promoters, the locations of the binding sites have been converted to absolute positions (as opposed to relative to a promoter), and the new slot ABS-CENTER-POS replaces the old slots REGULATED-PROMOTER and RELATIVE-CENTER-POSITION, which are now deprecated.

  A new flat file, regulation.dat describes all Regulation objects, with the attributes as described above. The files promoters.dat, dnabindsites.dat, proteins.dat, enzrxns.dat and compounds.dat have all been changed also to the extent necessary to incorporate the above changes.

  These schema changes allow for the representation of additional forms of regulation as well, which will be introduced in the next Pathway Tools release in early 2008.

• Pathway Tools has new support for representing, editing, and displaying electron transport information. The newly introduced Electron Transport Reactions (ETRs) are used to represent the electron transport processes that occur in membrane-associated enzyme complexes, involving membrane-bound electron carriers. These processes are important for energy generation by the cell, by using high energy electrons carried in certain substrates to increase the proton gradient across the membrane. A new graphical diagram for an ETR visually conveys the key features of such processes, like the direction of the electron flow and the cell compartment locations of where the substrates are transformed.

  To capture the complex processes in at least some detail, and to reuse recurring subreactions, ETRs are represented as novel composite reactions that are composed of Redox Half Reactions (RHRs). RHRs have a numerical standard reduction potential value associated with them, which determines the direction of the electron flow. The left and right side substrates of the ETR are inferred computationally from the RHRs used to construct the ETR. The Reaction Editor was augmented with 2 new modes, to allow creating and editing of RHRs and ETRs. Support for ETRs is still somewhat experimental, and while several examples are present in EcoCyc, more extensive curation will occur for the next release. Feedback is welcome.

• The Pathway Tools genome browser now has a zoom bar near its navigation control to facilitate larger changes in magnification of the genome view.

• A number of improvements have been made to the Regulatory Overview released in version 11.0.

• A tooltip window now appears on mouseover of active regions of a display.

• Many reliability improvements have been made to Pathway Tools, in particular to its Web mode.

Changes to PathoLogic

Release Notes for Pathway Tools Software Version 11.0

Released on March 23, 2007

General Changes

• New Genome Overview. This tool provides a one-screen view of every gene on one or more chromosomes and plasmids, and can display omics data across those entire replicons. The current version works in desktop mode only, through Overviews->Show Genome Overview. In the next release of Pathway Tools, the Genome Overview will work through the Web as well. To see the Genome Overview, click here. (See User's Guide Section 3.8.2.4.)

• New Regulatory Overview. This tool displays the transcriptional regulatory network of an organism that is defined in a PGDB. The network can be interrogated in several ways, such as highlighting all genes under a specified Gene Ontology class, and highlighting all genes regulated by a specified transcription factor. The current version works in desktop mode only, through Overviews->Show Complete Regulatory Overview. In the next release of Pathway Tools, the Regulatory Overview will work through the Web as well. To see the Regulatory Overview, click here. (See User's Guide Section 3.8.2.3.)

  The Regulatory Overview depends for its operation on an encoding of the organism's transcriptional regulatory network within a PGDB. Currently, EcoCyc is the only BioCyc PGDB that contains such a regulatory network. PGDB authors can define such a network manually using the interactive editors within Pathway Tools.

• Specify enzymes not used in pathways. A new slot Enzymes-Not-Used complements slot Enzyme-Use. The new slot allows a curator to specify enzymes that are known to not be used in a given metabolic pathway. This slot is accessible through the Pathway Info Editor.

• Catalytic domain protein feature. A new type of protein feature called a catalytic domain allows a PGDB to specify what region of a protein catalyzes which reaction of the protein. This type of feature is particularly useful for multifunctional proteins. These features may be created through the protein editor.

• Automatic patch loading. Whenever Pathway Tools starts up, it now performs its Instant Patch command, so that users will always be running the latest set of patches. This change has negligible impact on startup speed. But if needed, this behavior may be disabled by removing the option "-patch" in the script file pathway-tools under the aic-export/pathway-tools/ptools/* sub-directory.

• Compound display coordinates are now integers rather than real numbers to improve performance. Conversion to the new format is performed automatically when you open a PGDB under Pathway Tools 11.0.

Changes to the Pathway/Genome Navigator

• Tracks in genome browser. The Pathway Tools genome browser now supports tracks, in a manner similar to other genome browsers. Tracks allow genome regions defined in a GFF input file to be graphically highlighted in the genome browser. For more information see Chromosome->Add External Track and Section 3.8.11 of the User's Guide.

• Metabolite tracing. A new metabolite tracing tool allows you to visually trace the path of substrates through the metabolic network within a PGDB, using the Cellular Overview diagram. To see an example of metabolite tracing, click here. (See User's Guide Section 3.8.2.10.)

• Monitor sizing. Through both the desktop and Web versions, Pathway Tools now knows the size of your monitor. For example, this allows you to create very large genome browser displays by reshaping your Web browser to the full screen.

• Display of protein features on protein pages has been improved.

• Gene ontology assignments (both GO and MultiFun) are now displayed on gene-product pages in addition to gene pages.

• Line wrapping of publication references has been fixed.

• Gene-reaction schematic displays in MetaCyc are broken into different sections for each organism.

• New commands Proteins->Search by GO Term and Proteins->Search by MultiFun Term are available.

• The cellular overview diagram can now highlight items stored on the Answer List

• New BioVelo Query Language. We introduce a new advanced query language for querying PGDBs called BioVelo. BioVelo replaces the old Advanced Query Page. Users can construct BioVelo queries interactively through the BioCyc Advanced Query Page [documentation], and they can construct textual queries using BioVelo language [documentation].

• Google searching. The Navigator query page now contains a section for performing a Google-based search of the PGDB, which uses Google's index of a PGDB to perform arbitrary text searches against the PGDB. By default, this is enabled only for installations that serve from port 80. If you serve from another port and wish to add this search box, or if you serve from port 80 but your site is not indexed by google, you can change the default behavior with the command-line arguments -google-text-search or -no-google-text-search.

• New All-Search box. An All-Search box is now present at the bottom of every PGDB web page to allow users to perform a new search without first clicking to the query page.

• Name mouse-overs. Mouseover of compounds, genes, and proteins will additionally show all object synonyms.

Changes to the Pathway/Genome Editors

• Enzyme name editing. A button Edit Enzyme Name has been added to the Protein Editor to allow the enzyme name (as separate from the enzyme activity name) to be edited directly, and to clarify precisely when this should be done. See section 7.6.3.5 of the User Guide for more notes on this.

• External databases. The editors now contain a command for creating or editing the descriptions of external databases for use in PGDB links to those databases. New databases can be added with the command File->Create->External Database. Existing database records can be edited by right-clicking on any link to that database and selecting the command Edit External Database Info.

Changes to PathoLogic

Release Notes for Pathway Tools Software Version 10.5

Released on September 12, 2006

General Changes

• Ontology upgrade for signaling interactions: The Pathway Tools ontology has been enhanced in several respects to provide better support for the types of molecular interactions involved in signaling pathways. When you open your existing PGDBs under Pathway Tools 10.5 for the first time, their schemas will be automatically upgraded to reflect these changes.

• Consistency checker: A set of tools are now available to perform consistency checking and computation of cached data, for a PGDB. The consistency checking tools search for many common types of malformed data within a PGDB, and report their findings through a graphical interface. In many cases the tools repair these malformed data automatically. In other cases, the user must repair the data manually, but is guided in how to do so by the tools.

  In a number of cases, PGDBs cache data that are computed from other data within the PGDB. For example, a PGDB can cache molecular weights computed from the amino acid sequence of the organism, and can cache bulk statistics about the PGDB such as the number of pathways and enzymes. Tools are provided for recomputing these data based on the current state of the PGDB.

  These tools are accessed through the command Tools->Consistency Checker.

Changes to the Pathway/Genome Navigator

• Generate metabolic map poster: Pathway Tools can now automatically generate a poster-size version of the cellular overview diagram from any PGDB that includes the names of pathways, enzymes, genes, and metabolites. The diagram is generated as a postscript file using the command Overview->Print as Poster.

• Generate genome poster: Pathway Tools can now automatically generate a genome map poster using its genome browser, for any replicon in a PGDB. The diagram is generated as a postscript file using the command Chromosome->Print poster of chromosome.

• Zooming in overview: The Pathway Tools overview diagram now has semantic zooming capability -- as the user zooms to higher magnifications, first arrowheads, then pathway and metabolite names, and finally enzyme names appear.

• Sequence retrieval tool: A new tool for retrieving regions of nucleic acid sequence for a given replicon has been implemented. It is available through the command Chromosome->Show Sequence of a Segment of Chromosome

• BioPAX export: A new desktop-mode command is provided called File->Export->Entire DB to BioPAX file

• Pathway page BioPAX: Buttons are now provided on pathway display pages to generate for a given pathway:
  • The BioPAX-format encoding of the pathway

  • A list of all genes in that pathway

Changes to the Pathway/Genome Editors

• New reaction editor: The Pathway Tools Reaction Editor has been completely reimplemented to provide a more intuitive interface for editing biochemical reactions. In addition to providing the ability to enter metabolic reactions and transport reactions, the new Reaction Editor can also edit reactions involved in signal-transduction pathways. This editor is a major step toward full support for signaling pathways within Pathway Tools.

• Compound duplicate checking: The Compound Editor now checks if a newly created chemical compound is a duplicate of an existing compound in either the current PGDB or in MetaCyc, by searching both the names and chemical structure of the new compound.

• Spelling checker: The Pathway/Genome Editors now include a spelling checker that is run on text fields such a comments. It is temporarily disabled until a small glitch is fixed, at which point it will be enabled via a patch. Watch for a "spell check" button near comment entry panes, such as in the protein editor.

Changes to the PathoLogic

Release Notes for Pathway Tools Software Version 10.0

Released on March 15, 2006

General Changes

• Support for Gene Ontology. Pathway Tools now provides display, editing, and schema support for Gene Ontology. Users can assign Gene Ontology terms to genes within a PGDB using the Pathway Tools gene editor.

• New author crediting system. This new system within Pathway Tools allows curators to annotate pathways and proteins with information about who curated and reviewed these data within a PGDB, and when literature searches were last performed. Information about last curation and review dates are displayed within Pathway Tools display pages, and provide a way of crediting collaborators who assist with PGDB curation. Information about last literature-search dates are useful for tracking how up to date are annotations within a PGDB, and what entities should be curated next.

• Improvements to relational database support. The Pathway Tools distribution containing all three Pathway Tools components (Navigator, Editors, and PathoLogic) should now be able to access PGDBs stored in Oracle and MySQL, on the Sun/Solaris, Linux, and Windows platforms. The Oracle-related bug that prevented reliable access to PGDBs stored in Oracle by Pathway Tools version 9.5 has been fixed by a new release of the Oracle InstantClient library.

• New ptools-local directory. In previous versions of Pathway Tools, PGDBS created by users with PathoLogic were stored within the aic-export directory structure that also contained the Pathway Tools software. In version 10.0, the storage location for user-created PGDBs changes to be within a new directory called ptools-local that resides outside the aic-export directory. The ptools-local directory is shared by all users who share a given installation of Pathway Tools, and is retained when new versions of Pathway Tools are installed later. The user specifies the location of the ptools-local directory during the installation process. It can reside anywhere, such as in the home directory of one user of Pathway Tools, or in a more central location. As well as containing PGDBs, ptools-local contains other user data such as the new Pathway Tools initialization file.

• New Pathway Tools initialization file. A new initialization file called ptools-local/ptools-init.dat contains site-specific definitions of Pathway Tools parameters, and is shared by all users who share a Pathway Tools installation. This file must be manually configured by the installer of Pathway Tools.

• aic-export directory structure changed. The structure of the aic-export directory structure containing Pathway Tools has been altered in a number of ways.

• Auto-checkpointing of PGDB updates. For PGDBs stored in a relational DBMS (but not for file PGDBs), Pathway Tools now has an auto-checkpoint capability such that every 5 minutes it automatically checkpoints to a file all PGDB updates that have been made since the last DB save operation. Should the system crash, those updates can be restored by opening the PGDB and executing File->Restore Updates from Checkpoint File.

• New command-line arguments -eval and -load. Pathway Tools recognizes two additional command-line arguments when invoked from Unix: -eval and -load. The former evaluates a specified Lisp expression; the latter loads and evaluates all Lisp expressions within a specified Lisp file.

• User preference defining RDBMS username. A new user preference, under general preferences, allows the user to set the username that will be recorded in save transactions for PGDBs stored in relational DBMSs. This preference is useful when the same user has different computer accounts with different usernames, but wants all their save transactions to be recorded with the same username.

• PTOOLS_RDBMS_LOGIN obselete. This environment variable was previously used to supply relational DBMS login information to Pathway Tools, but is no longer used in favor of two variables in the Pathway Tools initialization file: RDBMS-Username and RDBMS-Password.

Changes to the Pathway/Genome Navigator

• Extensions to Reactions -> Find Rxn by Substrates. This command has been extended to permit more versatile searching of reactions by their substrates, such as searching for reactions based on combinations of exact substrates, chemical substructures within substrates, and substrate chemical classes.

• Compound windows link to regulated enzymes. Compound display windows now list those enzymes that are activated or inhibited by the compound, and those enzymes that require the compound as a substrate.

• Gene and protein windows show sequence length. Gene and protein sequence lengths are displayed in gene and protein display windows, respectively.

Changes to the Pathway/Genome Editors

Release Notes for Pathway Tools Software Version 9.5

Released on September 30, 2005.

General Changes

• New Interfaces to Oracle and MySQL: To facilitate (1) concurrent multi-user editing, (2) auditing of all edits, and (3) faster data access, we've added the option of storing user-created databases in an Oracle 10 or MySQL 4 server. (We haven't tested with Oracle 9.) Previously, Pathway Tools on the Solaris operating system came with an option to use Oracle 8, which is now quite outdated.Now, each curator can run Pathway Tools on their Solaris, Linux, or Windows computer without concern for which operating system other curators of the same database are using, assuming your database administrator installs Oracle or MySQL on a different computer than those computers running Pathway Tools. For more information, and for information on these RDBMS options, see URL http://bioinformatics.ai.sri.com/ptools/installation-guide/released.

• Pathway Tools now uses a new ontology of cellular components to describe cellular locations, such as protein locations, and locations of molecules that are substrates of transport events. A web site describing this ontology will be available shortly at URL http://bioinformatics.ai.sri.com/CCO/.

• The pathways.dat flatfile now includes super-pathways.

Changes to the Pathway/Genome Navigator

• Enhancements to the Cellular Overview diagram:
  • The Web version of the Overview Diagram (example) now provides more interactivity: when a compound icon in a pathway is clicked on, a magnified image of the pathway appears, including all compound names and genes, as well as a menu offering a choice of where to navigate to.

  • Display of Omics data on individual pathways: In the web version of the Omics viewer, Omics data is superimposed on magnified pathway diagrams within the Overview, including showing different colors (data values) for different isozymes where appropriate. There is also the option of generating a table of individual pathway displays for all pathways whose Omics values exceed a specified threshhold. In the desktop version of the software, navigating to an individual pathway page after uploading Omics data to the Overview will show the data on that pathway.

  • The web version of the Omics Viewer now offers a three-color display option in addition to the previously available full color spectrum. This capability was already available in the desktop version of the software.

  • The Omics Viewer now provides instructions for saving the generated display (including animation and/or pathway popups) to your local disk as an html file.

• New Comparative Analysis capabilities
  • The Comparative Genome Browser can be used to examine several replicons (chromosomes or plasmids) simultaneously side-by-side. This allows easy visual comparison of related organisms to observe similarities and differences in their gene arrangements. Orthologous genes are shown in the same color across the organisms. As an example, the trpA gene is aligned here for 3 E. coli strains and one Shigella strain.
    • NOTE: Ortholog information for all BioCyc DBs will be available through the SRI Web site by October 2005. However, ortholog information in the desktop (downloadable) BioCyc is only available for several E. coli related DBs in version 9.5; later versions will contain expanded ortholog information.
  • New Summary Tables compare various attributes relating to reactions, pathways, transcription units, etc. across a specified set of organisms. Note that this functionality is available through the Web mode of Pathway Tools only, that is, you must run Pathway Tools using the -www option to access this functionality.

  • The Cross-Species Comparison button in reaction and pathway displays allows a particular reaction or pathway to be compared across a selected list of organisms.

• The previously separate display pages for a polypeptide and its homomultimeric complex were combined into a single page.

• The Web Query page now allows search by accession number or id from any other database we link to. For example, typing P76078 (a swissprot link) or EG13736 (an ecogene link) into the search box will retrieve the protein or gene that has a unification link to that id (exact match only).

• The Query Results web page now includes a description of what kind of data appears in each type of web page. It also includes links to transcription unit pages.

• Pathway Tools can now generate a Genbank file describing the contents of a PGDB. Because Genbank format was not designed to capture the full range of information within a PGDB, our Genbank file export capability can only partially capture the contents of a PGDB. The exporter can be invoked using the command File->Export->Selected Chromosome to Genbank File...

• Improvements to the new genome browser:
  • The extent of transcription units (operons) is now shown by a grey background color; in addition, genes are colored to reflect membership in transcription units. Mousing over the grey transcription unit region will produce a pop-up showing what transcription factors control the expression of that transcription unit.

  • To re-center the magnified region of the chromosome on a given gene, click on a tick mark under that gene.

• The new command File->Summarize Current Organism displays the organism summary page for the current organism.

• Added new command invoked by right-clicking on an object called Show->Frame in all databases, and renamed right-click Show->Frame in other species to Show->Frame in other database.

• Base position in gene page is now displayed as start arrow end where start is always the smaller base position and arrow indicates the direction of transcription. Examples:
  • 300,001 -> 300,901
  • 200,001 <- 200,601
• In the desktop version, the information in all Database Links can be shown by right-clicking. The creation-date of the link is also shown now.
• Start codons are now denoted in FASTA sequence output in a different case than the remainder of the sequence.

• Transcription unit figures now show promoters and binding sites with low quality evidence using a dashed outline (as opposed to a solid outline for those with high quality evidence).

Changes to the Pathway/Genome Editors

• New Marvin chemical structure editor: The Marvin molecular structure editor java applet has been integrated with Pathway Tools for use as a chemical structure editor. Users now have a choice of using either Marvin or the JME editor. Relative advantages of these two tools are that JME is very simple to use, but Marvin is much more feature-rich. Marvin can be used for entering compound structures with atoms called R, R1, R2, etc., by using the atom-alias feature. For more information see page 81 of the Pathway Tools User's Guide vol.II. Also, it is now possible to clear and completely delete a chemical structure in a PGDB, using Marvin or JME.

• Users can now enter hyperlinks to other PGDB objects within the comment text for any object, allowing clickable references to other PGDB objects to be embedded within comment text.

• To remove an association between an enzyme and a reaction it catalyzes, right click the protein and, in the menu that pops up, select: Edit->Remove Reaction

• To merge two reactions into a single frame, right-click on one of the reactoins and select: Edit->Merge Reactions

Changes to PathoLogic

• Inference of Transport Reactions: PathoLogic contains a new inference module called the Transporter Identification Parser that infers transport reactions within a PGDB from free-text descriptions of transporter function. Inference of transport reactions is valuable because transport reactions allow Pathway Tools to compute with the functions of transporters, such as to add transporters to the Cellular Overview diagram automatically.

  Developed in collaboration with Dr. Ian Paulsen of TIGR, this program performs a textual analysis of the English descriptions of protein function within a PGDB stored within the Common-Name field of each protein. It determines which proteins are transporters, what is the transported substrate and the direction of transport, and what energy coupling mechanism is employed by the transporter. When the program is able to identify all of these fields it creates a reaction object within the PGDB that precisely describes the transport event that the transporter achieves. An example reaction for an ABC transporter for L-lysine for a Gram-negative bacterium is:
  L-lysine [periplasm] + ATP = L-lysine [cytoplasm] + ADP + P_i
  That is, the transporter moves L-lysine from the periplasm to the cytoplasm in conjunction with hydrolysis of ATP.

  A user interface permits review and editing of individual transport reactions.

• PathoLogic is now supported on Windows 2000 and Windows XP. Now, essentially all of Pathway Tools runs on three operating systems: Linux, Solaris, and Windows. NOTE: Due to factors (bugs) beyond our control, release of the Windows version of the full Pathway Tools including PathoLogic will be delayed; we will make an announcement when this build is available thorugh our download site.

• PathoLogic now properly recognizes and processes pseudogenes. PGDB objects are created for pseudogenes, but no objects are created for the gene products since no gene products are produced. See the manual for details on how to specify pseudogenes in the input files.

• PathoLogic can now use other organism PGDBs as additional references for pathway prediction. For examle, if you have curated new pathways into a PGDB you have created, and you wish to create a second PGDB, you can tell PathoLogic to consider pathways in both MetaCyc and in your first PGDB for possible prediction in the second PGDB.

Release Notes for Pathway Tools Software Version 9.0

Released on Feburary 22, 2005.

General Changes

• The Microsoft Windows version of Pathway Tools is easier to install.

• The Microsoft Windows version of Pathway Tools is now easier to run as a web server.

Changes to the Pathway/Genome Navigator

• New Genome Browser: Chromosomes and plasmids can be examined in a new horizontal genome browser. For example, see the browser centered around gene dnaA. Some of the key features are:
  • At the top of the page, the full length of the chromosome is shown at low resolution. A selected region of the chromosome is displayed at higher magnification in the lower part of the screen.
  • The full chromosome view at the very top indicates the magnified region by means of a red, rectangular cursor.
  • Magnified regions can be wrapped over several lines, thus showing more context.
  • Several levels of semantic zooming show increasing detail upon increased magnification.
  • Protein ORFs are visually distinguished from RNA genes, and when genes belong to the same operon, they are assigned the same color.
  • An improved navigation interface offers a panel of control arrows that allow translation and zooming. Additionally, basepair positions or a gene name can be manually entered into text entry boxes to position the browser.
  • Mouse-over of genes shows gene names and intergenic distances to the neighbors in basepairs. Mouse-over of promoters shows the activating and inhibiting transcription factors.

• Improved operon depiction in gene pages: The transcription unit diagram at the bottom of gene pages has been modified to show more of the genome context around a given gene -- it shows the entire operon of the gene, and surrounding genes. Additional diagrams showing all of the gene's transcripts are now generated, and are aligned to the first diagram. For example, see the display for gene dnaA

• More compact pathway diagrams: The pathway-drawing capabilities have been improved so as to produce more compact diagrams in many cases. For example, see this pathway.

Changes to PathoLogic

• Pathway Hole Filler: In the "Candidates to Fill Pathway Hole" page, which displays for each candidate a summary of the evidence used to evaluate the candidate, we have replaced the lists of reactions associated with the candidate and the pathway hole with a Gene-Reaction Schematic for each. The Gene-Reaction Schematic for the candidate displays the candidate and its associated reactions in the user's KB. The schematic for the pathway hole displays the missing reaction and its associated reactions and genes in MetaCyc. A comparison of these two schematics will assist the user in deciding which candidate(s) to assign to each pathway hole.

Release Notes for Pathway Tools Software Version 8.5

Released on September 17, 2004.

General Changes

• Pathway Tools and BioCyc licensing, which formerly required a paper license agreement, are now processed entirely online at http://BioCyc.org/download.shtml.

• Cellular Overview and Omics Viewer Improved: The Cellular Overview diagram within Pathway Tools has been improved in many respects, and the Expression Viewer has been renamed the Omics Viewer to reflect its expanded functionality. See for example the E. coli Omics Viewer. Improvements include:
  • Users can create combined displays of gene expression, proteomics, metabolomics, and reaction flux measurements on the Omics Viewer
  • Drawing speed is improved
  • Metabolic pathways in the Overview are now grouped by pathway class, with additional information shown on mouse-over
  • Zooming of the diagram is supported (desktop version only)
  • The periplasm and outer membrane have been added to the diagram, as have those proteins present in the periplasm and outer membrane
  • The layout of the Cellular Overview can be computed completely automatically by PathoLogic in a new PGDB, obviating the need for users to manually lay out the diagram

• Compound Stereochemistry: Pathway Tools now supports stereochemistry for chemical structures in its schema and in its display of chemical structures. Many chemical compounds in our PGDBs now contain stereochemical information in their structures. Editing of chemical structures is now supported via the JME chemical editor.

• JME Chemical Editor Now Supported: Pathway Tools now provides an interface to the JME chemical editor. JME was written by Peter Ertl of Novartis. It supports editing of stereochemistry, and is generally superior to the native chemical editor provided by Pathway Tools, therefore SRI now encourages the use of JME instead of the old editor. JME is not included in the Pathway Tools distribution, but may be obtained from Novartis. It is freely available for academic users -- see http://www.molinspiration.com/jme/doc/index.html. Instructions on how to install it for Pathway Tools are in Section 2.3.8 of the Pathway Tools User Manual, Volume II.

• Import/Export from/to Molfiles: Chemical structures can now be imported from and exported to the molfile format. This functionality is available under the Edit menu when the user right-clicks on a compound. To use this feature, right click the title of a compound display, and select one of:
  • Edit > Import compound structure from molfile...
  • Edit > Export compound structure to molfile...

Changes to the Pathway/Genome Navigator

• Ontology Viewer Improved (web version): Web pages depicting ontology class hierarchies now use an improved hierarchy browser. See for example the MetaCyc pathway ontology.

• Web Pages Listing Compounds, Enzymes, and Genes: The Web Query Form now allows the user to generate alphabetical listings of all pathways, proteins, genes, and chemical compounds for the selected PGDB, in the third main bullet in this page.

• Species Abbreviations in MetaCyc Pages: In MetaCyc display pages for reactions, pathways, etc, it can be difficult to tell the source species for a given enzyme or gene. Therefore, MetaCyc display pages now include a two-letter species code in gene and enzyme names consisting of the first letter from the genus and species name. For example, the enzyme phosphoglycerate kinase and its gene pgk from Pseudomonas aeruginosa would be depicted as phosphoglycerate kinase (Pa) and Pa-pgk, respectively.

• Changes to Gene-Regulation Schematic: The gene-regulation schematic diagram in pathway pages summarizes genetic regulatory relationships for all genes in a pathway. The node and edge shapes in the diagram have been updated to use more standard conventions for depicting activation, inhibition, and dual regulation.

Changes to PathoLogic

• Pathway Hole Filler: The user interface for the third step of the Pathway Hole Filler (Choose Candidate Holes to Fill in KB) has been completely overhauled to make the process more straightforward and efficient. In the new version, the interface provides the opportunity to review the evidence for all candidates identified for each pathway hole. The first page displays for each pathway hole the top scoring hit above a cutoff determined by the user. From this page, the user may access another window (Candidates to Fill Pathway Hole) which displays for each candidate a summary of the evidence used to evaluate the candidate. This page also includes other data available in the KB for the candidate (e.g., other reactions catalyzed by the candidate) and the pathway hole (e.g., all pathways where the reaction is missing). The process of manually reviewing each candidate and choosing which holes to fill has been drastically streamlined by gathering all the relevant information into one page.

• PathoLogic Accepts NCBI Taxonomy ID: Users can supply the NCBI Taxonomy ID of the organism to which PathoLogic is being applied in the database-creation dialog to facilitate linking of the PGDB to the NCBI Taxonomy database.

Release Notes for Pathway Tools Software Version 8.0

Released on March 12, 2004.

General Changes

• Napster Comes to Bioinformatics: A peer-to-peer sharing mechanism for Pathway/Genome Databases (PGDBs) has been implemented for Pathway Tools. This mechanism consists of a registry server running at SRI that maintains a list of PGDBs that have been registered for sharing. You can use the Pathway Tools program to register PGDBs that you have created for sharing (they are deposited on your own FTP site for downloading by others), and to download PGDBs listed on the registry. You can view the current contents of the Registry on the Web at URL http://biocyc.org/registry.html, or from Pathway Tools 8.0 with the command: Tools->Browse Downloadable PGDBs. We encourage you to register PGDBs that you have created, using the command Tools->Publish PGDBs. For more information, see the Pathway Tools User's Guide.

• Pathway Hole Filler: Metabolic pathways that were computationally predicted by PathoLogic often contain reactions that have no identified enzymes within the genome. We call those reactions pathway holes. A new Pathway Tools prediction algorithm that you can run on an existing PGDB predicts which genes within the genome code for enzymes that fill these holes. When applied to a microbial genome, it can generate 50-100 new gene function identifications. A manuscript describing this algorithm is available here. For more information, see the Pathway Tools User's Guide.

• Protein Features: Pathway Tools now supports editing and display of protein features. The protein editor allows users to define many different types of protein features on a protein, such as metal binding sites, disulfide bond locations, chemically modified residues, homology domains, repeats, signal sequences, DNA binding regions, and transmembrane regions. To add a new feature to a protein, right-click on the name of the protein in a Navigator display, and select Edit->Add Feature. Features are displayed schematically in Navigator protein display windows.

• Oracle passwords: For users who have stored newly created PGDBs within an Oracle server, Pathway Tools no longer requires a fixed Oracle login and password. The following pertains to the Unix environment variable PTOOLS_ORACLE_LOGIN: If the environment variable is:
  • Set to "PROMPT", the software will prompt the user for login/passwd
  • Set to anything else, the software use that value as login/passwd
  • Unset, the software will use the previous hardcoded value

Changes to the Pathway/Genome Navigator

• Navigator main menu redesigned: (Desktop version) The main menu of the desktop version of the Navigator has been completely redesigned. Rather than having query modes such as "Compound Mode," queries are now accessed from a menu-bar whose items include "Compound," "Pathway," etc. This approach is more familiar to most users, and frees up screen real estate.

• Protein display windows redesigned: (Web and desktop) The protein display windows have been redesigned in several respects. The polypeptide display window now displays information about a complex that contains it, much as a complex window contains information about its subunits. The styling of subunit composition has been re-worked somewhat. And in displays of transcription factors, information about all modified forms of the transcription factor are shown on one page.

• New queries: (Desktop) The following new queries have been implemented:
  • New RNA navigation features include Get RNA by name, Get RNA by Substring, Get RNA by Class.

• Retrieve arbitrary DNA sequences: (Web) We have added the ability to retrieve or zoom to arbitary DNA sequence regions from gene pages. Click on the button "Nucleotide Sequence Neighborhood" near the top of each gene page.

• Small map updated: (Web and desktop) The small genome map displayed below a pathway drawing has been improved to print more meaningful information when the user moves the mouse over the tick marks that represent genes within the pathway.

• New Overview metabolite shape: (Web and desktop) We have added a new compound shape to the Overview diagram: upside-down triangles represent cofactors.

Changes to the Pathway/Genome Editors

• The reaction editor now supports fractional coefficients.

• Several bugs in the Create/Add Protein dialogs have been fixed.

• The compound structure editor has been modifed to use a horizontal menu bar instead of the older vertical menu.

• The reaction balance checker has been modified to tell the user that it does not try to balance hydrogens due to the complications with respect to portraying compounds in their correct ionization states, for example, different compounds in our databases are stored in different somewhat inconsisetent ionization states, making balancing of reactions with respect to hydrogens very difficult.

Changes to the PathoLogic

• New batch mode: PathoLogic can now operate in batch mode, meaning that it can automatically create PGDBs for one or more organisms based on invocation from the Unix command line. The command-line invocation specifies a directory that PathoLogic should examine to find input files, such as one or more Genbank files for the PGDB to create. The fact that this processing is completely automated means that the resulting PGDBs lack elements that are created manually, such as an Overview diagram. For more information, see page 1-38 of the Pathway Tools User's Guide, Volume II.

Release Notes for Pathway Tools Software Version 7.5

Released on August 29, 2003.

General Changes

• A general import/export facility for frames has been added. Sets of frames can be exported to and imported from character-delimited files, which can be imported into a spreadsheet program, edited, and re-imported. Frames can also be exported to an attribute-value format similar to MEDLINE format, and re-imported into a different KB.
• The bug report form has been changed to make it easier to use.
• It is now possible to install Pathway Tools with any of the buttons on the main query page (help, pathway tools home, etc.) redirected to a custom user-specified URL.
• An ontology of evidence codes has been added to the Pathway Tools schema, in order to capture the evidence (computational, experimental, type of experiment, etc.) for the existence of various entities (pathways, protein functions, transcription units, etc.) in an organism. Pathway Tools has been extended so that the pathway and operon predictors within PathoLogic decorate the pathway and operon PGDB objects that they create with evidence-code information, indicating computationally predicted objects as such. The Editors have been extended to include functionality that allows users to interactively enter and modify evidence codes within PGDB objects. The Navigator has also been extended to display evidence information.

Changes to the Pathway/Genome Navigator

• Desktop mode (not Web mode): Several new types of queries have been added:
  • Query pathways by reactants and products.
  • Query proteins by molecular weight and pI.
  • Query compounds by conjunctions of name, molecular weight, chemical formula, and substructure properties.
• The bottom of each Pathway Tools object display page now shows the full reference list for all references cited in that page. In desktop mode, a new preference under the Preferences menu allows the user to influence how citations are displayed (e.g., "[1]" vs "[Smith85]").
• Displays of the parent classes of an instance have been reworked to be more intuitive; they now show the complete class inheritance path back to the roots of the class hierarchy.
• Web mode: A new "All" query is available, allowing users to query all object types by substring with one query. The matching objects are grouped by object type (pathways, proteins, etc).
• The list of reactions in the compound display is sorted according to the role that the compound plays in each reaction.
• MetaCyc's pathway displays now has an option to show all enzymes for reactions, even for organisms that do not have the pathway.
• Display of chemical structures has been improved.

Changes to the Pathway/Genome Editors

• There is now an editor for RNAs, which also allows the creation of RNAs for genes.
• The compound structure editor now allows charges to be entered along with each atom.

Release Notes for Pathway Tools Software Version 7.0

Released on February 28, 2003.

General Changes

• The set of flat-file dumps has been expanded somewhat to contain some additional files, and additional fields per file. Comments and citations are now included in the flat files, and there is a new Publications flat file.
• Pathway Tools now supports introns, exons, and alternative splice forms in its display and editing tools.

Changes to the Pathway/Genome Navigator

• Consider the display of a MetaCyc pathway for which data from multiple enzymes from different species is available. Initially the pathway display shows all enymes, but you can use a menu at the top of the pathway page to generate a species-specific views that shows only the enzymes from that species.
• The expression viewer can now load expression data in the format used by the SAM program for Significance Analysis of Microarrays (see URL http://www-stat.stanford.edu/~tibs/SAM/)
• Desktop mode (not WWW mode): Right-clicking on a database link allows you to request additional information about that link.
• Desktop mode: The Overview scaling size preference is now properly saved across sessions.
• WWW mode: You can now query multiple objects by name or identifier simultaneously in the Pathway Tools query form, by entering their names or identifiers, separated by commas
• Chemical Abstracts registry numbers are now implemented in all DBs as database links, rather than as a field in the schema.
• You can view the user guide using a command under the Pathway Tools help menu "Show User Guide"
• WWW mode: The Pathway Tools WWW server now attempts to detect and block web crawlers
• It is possible to run a Pathway Tools WWW server in a mode whereby it suppresses display of gene pages for an organism by generating URL links to another genome database for the organism. This mode allows an existing genome database to interoperate closely with a pathway database for the organism managed by Pathway Tools. See the section on invoking Pathway Tools in the User's Guide for more information.

Changes to the Pathway/Genome Editors

• The chemical compound structure editor has been documented in the User's Guide, and the tool been overhauled and extended. This tool can be used to enter or modify small-molecule structures.
• The pathway editor now allows the user to add/delete arrow links between pathways, and to mark reaction steps as hypothetical.

Changes to PathoLogic

• A new command under the PathoLogic Organism menu allows the user to create a copy of an entire Pathway/Genome Database.

Release Notes for Pathway Tools Software Version 6.5

Released on August 30, 2002.

Changes to the Pathway/Genome Navigator

• The viewer for painting expression data on the full metabolic overview has been expanded to support animated display of multiple expression time-points, and to allow the user to specify the colors used for different ranges of expression values. Several bugs have been fixed in the expression viewer, performance has been improved, and better detection of malformed input files has been added.
• In previous versions of the Navigator, the WWW server capability that allowed the Navigator to publish Pathway/Genome Databases on the WWW ran only on the Sun. Now that capability runs on the PC/Windows platform as well.
• A Perl API called PerlCyc now exists to allow Perl programmers to query Pathway/Genome Databases. See the documentation for the Pathway Tools command-line argument "-api".
• We have expanded the set of flatfiles generated for Pathway/Genome Databases. Click Here for descriptions of the flatfiles.

Changes to the Pathway/Genome Editors

• The Editors can now export a pathway to a file, and import pathway from an exported file. See commands under Special->Misc.
• A publication editor has been added for defining new references in a PGDB.

Changes to PathoLogic

• A new command under the PathoLogic Organism menu allows the user to create a copy of an entire Pathway/Genome Database.

Release Notes for Pathway Tools Software Version 6.0

Released on February 25, 2002.

Changes to the Pathway/Genome Navigator

• The Navigator has been ported to Windows-98 and higher versions of Windows.

• A new facility called Auto-Patch allows you to easily download software patches from the SRI website. The command Special -> Misc -> Install Patches -> Download patches from the Web, will automatically download new software patches from the SRI Web site and load them into your running program. Auto-patch downloads will also occur whenever you install the software.

• A HELP button has been implemented for the Gene-Reaction Schematic, and for the Gene-Regulation Schematic.

• The Organism Summary Page for a given Pathway/Genome DB now includes a listing of the authors and their institutions, and a list of citations, for that DB.

• The local Navigator now allows retrieval of an arbitrary nucleic-acid sequence region (see Show Sequence command under Gene Map Mode).

• A new command-line option allows the user to specify the default organism to which queries will be directed within the Navigator in Web mode.

• Many bug fixes and performance improvements have been made to the Navigator, particularly to the gene-expression pathway viewer.

Changes to PathoLogic

• The documentation for PathoLogic and for the Pathway/Genome Editors has been completely overhauled.

• The PathoLogic graphical user interface has been completely rewritten to facilitate creation of new Pathway/Genome Databases.

• A new PathoLogic interface accessible through the command Refine -> Assign Probable Enzymes assists the users in manually assigning biochemical functions to gene products.

• The PathoLogic pathway evidence report has been improved significantly.

• The Pathway Tools has been upgraded to work in conjunction with Oracle 8i instead of version 7 of Oracle.

Release Notes for Pathway Tools Software Version 5.4

Released on February 10, 2001.

Changes to the Pathway/Genome Navigator

• The hostname in EcoCyc and MetaCyc URLs has changed from ecocyc.PangeaSystems.com to ecocyc.DoubleTwist.com.
• The ability to paint expression data onto the Overview is now available through the WWW. From the query page at http://ecocyc.DoubleTwist.com:1555/server.html, in the first line under "Links to summary information about the selected organism," click on "Expression viewer."
• The Overview visualization now depicts the cytoplasmic membrane and its transporters, for those transporters defined as database objects.
• The Navigator now produces displays of the transcription unit that contains a given gene, and of all transcription units controlled by a given transcription factor.
• The gene window now allows the user to retrieve both the nucleotide sequence of the gene, and the amino-acid sequence of the gene product.
• The chromosome viewer now contains active arrow keys for moving a child map up and down, and for changing the magnification of a child map. The viewer also now depicts promoters at high levels of magnification.
• The Highlight command within Overview mode now includes an option for highlighting reactions according to the cellular locations of the enzymes that catalyze a reaction.
• We have upgraded the look-and-feel of the WWW Navigator.

Release Notes for Pathway Tools Version 5.0

Released on June 1, 1999.

Changes to the Pathway/Genome Editing Tools

• The behavior of the right-click menu Edit->Create-And-Edit-Frame has been modified to allow the user to specify the class of the new instance.
• The GKB Frame Editor now supresses display of many slots that most users will not be concerned with. These slots can be displayed using a selector in the Frame Editor Preferences dialog.
• The Revert and Refresh KB operations now redisplay current Pathway Tools windows in case those operations altered the currently displayed objects.
• The Special->KB menu has been reorganized.
• When an asterisk ("*") is printed next to the name of an organism (such as in the organism-selector menu or in the window title line) it means that unsaved KB changes exist for that organism.

Changes to the Pathway/Genome Predictor (PathoLogic)

• PathoLogic now uses the MetaCyc database as its reference pathway database, thus significantly increasing the range of pathways it can predict for an organism.
• PathoLogic now properly copies its HTML summary reports into a directory that is accessible by the Pathway Tools in WWW mode.