• PathCase^KEGG : This system features KEGG metabolic pathways. That is, it contains in its database, KEGG metabolic pathways. The KEGG data in the PathCase^KEGG database is refreshed every year, via a license from KEGG.
• PathCase^alpha : This system features BioCyc human pathways. That is, it contains in its database, BioCyc human pathways. It is no longer updated in that we do not refresh its database with recent changes to BioCyc human pathways.
• PathCase^sample : This system features sample pathways from the literature, and is no longer updated.

II. PathCase Systems Biology Workbench

PathCase^SB System, currently being developed by a grant from NSF Biology, features PathCase Systems Biology Workbench that links metabolic pathways with systems biology models. The aim of the PathCase^SB project is to build a framework and tools towards effective and efficient systems biology model development for multiscale mechanistic models of biological systems. Our approach is to integrate the model database with our metabolic network database PathCase^KEGG in order to build “one-shop” querying, visualization, simulation, and modeling capabilities. While the PathCase^SB system is continually being improved and its database is being expanded, it currently has the following components:

• PathCase^SB Database that contains systems biology models from BioModels [BioM] and metabolic pathways from KEGG [Kegg],
• PathCase^SB Browser Interface is a web-based interface that works with popular internet browsers. Its goal is to provide a variety of browsing-based mechanisms for users to access the database, starting from a basic overview that lists the entities in the database to hierarchically drilled-down levels that us, among others, an advanced querying interface and even visualization in the form of a graph.

The browser interface is built primarily for viewing the information related to

(a) systems biology models from Biomodels [BioM, BioM06] (and later from other sources, such as CellML [CellML]) in conjunction with metabolic pathway fragments from KEGG [Kegg] that these models employ, and

(b) metabolic pathways from KEGG, in conjunction with BioModels models, with a focus on presenting the relationships that exist between the various entities of the two types i.e., models and pathways.

• PathCase^SB Visualization that allows visualizations of pathways modeled by specific models as well as cross-reference visualizations between models and pathways. The visualization, made possible via our PathCase graph Viewer, allows for curated layouts for improved model visualization.
• PathCase^SB Querying Interface is designed to allow users to pose built-in (i.e., predefined) or ad hoc (i.e., constructed by the user during a query session as needed) queries involving models and pathways. Currently, built-in queries, which can be characterized as a small set of queries that are the most popular ones by users, are implemented and available. Ad hoc queries are not yet implemented, and will be made available via the Advanced User Interface (AQI) [E+09].
• PathCase^SB Simulation Interface uses SBML-specified systems biology models as input, and provides web-based (i.e., internet browser-based) model-simulation capabilities. It currently has two simulation subsystems:

(a) SimCom (Simulation and Compare) Tool allows users to simulate one or more models for a chosen metabolic patway side-by-side and compare their simulations side-by-side. Users can also choose to change the parameters of the models for simulation with different set of parameters. Another novel feature of this tool is to allow users to add/change experimental values for the chosen pathways behaviour and compare the experimentally observed behavior of the pathway with the simulation results from chosen the model. This tool is aimed to be a basic building block and a major step forward in helping Systems Biologists in composing and designing new models for pathways.

(b) iModel (User-Uploaded Models) Tool allows users to visualize and use simulation and comparison features in PathCas^SB for their own models. Users can upload their model specified in SBML, using a user friendly interface (by just choosing the file to upload their file containing the model).

• PathCase^SB Provenance Tool provides provenance information for the data in PathCase^SB database. Provenance is defined as “metadata that tracks the steps of data derivation, which can add value to the data itself”. Since PathCase^SB System uses third party sources for most of its data (e.g., systems biology models from BioModels and metabolic pathwats from KEGG), it is important for users to assess the trustworthiness of the data used in PathCase^SB. For example, for a systems biology model, metadata information about (i) the creators of the model, (ii) the publication that have lead to the model, and (iii) the references of the model are crucial about assessing the trustworthiness of the model. Provenance subsystem of PathCase^SB aims to provide support for storage, querying and visualization of provenance for the data used by the system. PathCase^SB specifies provenance data as a stand-alone panel. When a model is selected by the user, and the provenance panel is “clicked”, the provenance tool shows the provenance data about the selected model.

III. PathCase Metabolomics Analysis Workbench

PathCase^MAW system, currently being developed by a grant from NSF Biology, features PathCase Metabolomics Analysis Workbench that is designed for metabolomics analysis. Towards this end, PathCase^MAW database contains a fully hierarchically compartmentalized metabolic network for mammalians (humans and mice). Full compartment hierarchy refers to the multi-tissue (e.g., liver, adipose tissue, muscle, etc) environment as well as a complete biological compartment distinction (e.g., liver-cell, liver-cytosol, liver-mitochondrion, etc.). The network is being entered manually via an editor.

Recently, we have developed three frameworks for automated analysis of metabolomics data in terms of the dynamic behavior of the metabolic network:

• Observed Metabolite Analysis (OMA) takes as input observed (measured) metabolite concentration increases and decreases within the metabolic network, and infers, as much as it can, those paths of reactions that “may” have increased and/or decreased fluxes in the metabolic network. The idea of the OMA framework is to (i) chase the implications of observed metabolite concentration increases and decreases within the metabolic network, and (ii) eliminate those metabolic network reaction paths with increased and/or decreased fluxes that could not have happened, and (iii) return those metabolic network reaction paths (with increased and/or decreased fluxes) that may have happened. The OMA framework does not deal with the steady-state of the organism and does not infer whether the reactions of the metabolic network are active or inactive at steady-state. OMA Tool in PathCase^MAW is available and functional.
• Metabolism Query Language (MQL) provides
  • An environment capable of capturing the inner working principles of metabolism under different constraints (such as dietary and physiological condition specifications), and
  • A query language capable of querying the dynamics of the metabolism, given a set of observed metabolite concentration increases and decreases within the metabolic network.

In more detail, MQL enables users to specify multiple and different classes of queries, such as (a) computing (and visualizing) “Activated/Inactivated (metabolic) Paths” with increased and decreased fluxes under specified physiological conditions (MQL_AIP queries), (b) identifying/verifying “Potential Futile Cycles”, (c) querying for required metabolic concentration change sets to prevent a particular futile cycle, (d) searching for concentration change sets which lead to the (in)activation of a user-specified metabolic subnetwork, and (e) exploring the metabolic behavior of a set of (possibly reversible) reactions. At this point in time, within the MQL framework, only MQL_AIP is being implemented.

• Steady-state Metabolic network Dynamics Analysis (SMDA) reasons about the dynamic behavior of the metabolic network at steady-state, and locate possible alternatives for active/inactive metabolic subnetworks. More specifically, SMDA (a) assumes that the organism has reached a steady-state, and (b) makes no assumptions about what the metabolite pool sizes are at the steady-state, or how the steady-state has been reached. Given that a set of bio-fluid (e.g., blood) metabolite concentration values and, perhaps, a number of tissue-based metabolite concentration values are measured at steady-state, the question that is addressed by the SMDA framework is “what type of alternative steady-state metabolic network dynamic behavior scenarios exist, given the measurements?”. Currently, the SMDA framework is being implemented.

PathCase is accessed from all around the world by anonymous researchers every day. The following map shows approximate locations of PathCase users.

The PathCase web client is a web-based interface to the PathCase Database, and provides a web-based toolset via a Java applet loaded within a browser window. It is designed as an intuitive and easy-to-use tool, with no need to study user manuals.

The PathCase Desktop Client is a desktop application for browsing and interacting with the PathCase database. The desktop client is discontinued, and the latest version can be found under the "Legacy Software" link on the left.