PathBuilder--open source software for annotating and developing pathway resources.
ABSTRACT We have developed PathBuilder, an open-source web application to annotate biological information pertaining to signaling pathways and to create web-based pathway resources. PathBuilder enables annotation of molecular events including protein-protein interactions, enzyme-substrate relationships and protein translocation events either manually or through automated importing of data from other databases. Salient features of PathBuilder include automatic validation of data formats, built-in modules for visualization of pathways, automated import of data from other pathway resources, export of data in several standard data exchange formats and an application programming interface for retrieving existing pathway datasets.
PathBuilder is freely available for download at http://pathbuilder.sourceforge.net/ under the terms of GNU lesser general public license (LGPL: http://www.gnu.org/copyleft/lesser.html). The software is platform independent and has been tested on Windows and Linux platforms.
Supplementary data are available at Bioinformatics online.
- SourceAvailable from: Jyoti Sharma[Show abstract] [Hide abstract]
ABSTRACT: Human thyroid stimulating hormone (TSH) is a glycoprotein secreted by the anterior part of the pituitary gland. TSH plays an important physiological role in the regulation of hypothalamic-pituitary-thyroid axis by modulating the release of the thyroid hormones from the thyroid gland. It induces iodine uptake by the thyroid, promotes thyroid epithelial differentiation and growth, and protects thyroid cells from apoptosis. Impairment of TSH signal transduction pathway leads to thyroid disorders such as goitre, hypothyroidism and hyperthyroidism, which can have complex clinical manifestations. TSH signaling is largely effected through two separate pathways, the adenylate cyclase and the phospholipase C pathways. In spite of its biomedical importance, a concise signaling map of TSH pathway is not available in the public domain. Therefore, we have generated a detailed signaling map of TSH pathway by systematically cataloging the molecular reactions induced by TSH including protein-protein interactions, post-translational modifications, protein translocation events and activation/inhibition reactions. We have cataloged 40 molecular association events, 42 enzyme-substrate reactions and 16 protein translocation events in TSH signaling pathway resource. Additionally, we have documented 208 genes, which are differentially regulated by TSH. We have provided the details of TSH pathway through NetPath (http://www.netpath.org), which is a publicly available resource for human signaling pathways developed by our group. We have also depicted the map of TSH signaling using NetSlim criteria (http://www.netpath.org/netslim/) and provided pathway maps in Wikipathways (http://www.wikipathways.org/). We anticipate that the availability of TSH pathway as a community resource will enhance further biomedical investigations into the function and effects of this important hormone.Journal of Proteomics & Bioinformatics 10/2011; 4.
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ABSTRACT: TEK tyrosine kinase is primarily expressed on endothelial cells and is most commonly referred to as TIE2. TIE2 is a receptor tyrosine kinase modulated by its ligands, angiopoietins, to regulate the development and remodeling of vascular system. It is also one of the critical pathways associated with tumor angiogenesis and familial venous malformations. Apart from the vascular system, TIE2 signaling is also associated with postnatal hematopoiesis. Despite the involvement of TIE2-angiopoietin system in several diseases, the downstream molecular events of TIE2-angiopoietin signaling are not reported in any pathway repository. Therefore, carrying out a detailed review of published literature, we have documented molecular signaling events mediated by TIE2 in response to angiopoietins and developed a network map of TIE2 signaling. The pathway information is freely available to the scientific community through NetPath, a manually curated resource of signaling pathways. We hope that this pathway resource will provide an in-depth view of TIE2-angiopoietin signaling and will lead to identification of potential therapeutic targets for TIE2-angiopoietin associated disorders.Journal of signal transduction. 01/2014; 2014:173026.
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ABSTRACT: Abbreviations CCKAR Cholecystokinin A receptor CCKBR Cholecystokinin B receptor ECL Enterochromaffin-like PPI Protein-protein interaction PTM Post-translational modification HPRD Human protein reference database SBML Systems biology markup language PSI-MI Proteomics standards initiative for molecular interaction BioPax Biological pathway exchange Yashwanth Subbannayya and Kumari Anuja contributed equally. Y. Subbannayya : J. Advani : V. Nanjappa : B. George : B. L. Somani : R. Raju (*)Journal of Cell Communication and Signaling 01/2014; 8:165-170.
BIOINFORMATICS APPLICATIONS NOTE
Vol. 25 no. 21 2009, pages 2860–2862
Databases and ontologies
PathBuilder—open source software for annotating and
developing pathway resources
Kumaran Kandasamy1,2,3, Shivakumar Keerthikumar1,2, Rajesh Raju1,2,
T. S. Keshava Prasad1, Y. L. Ramachandra2, Sujatha Mohan1,4and Akhilesh Pandey3,∗
1Institute of Bioinformatics, International Tech Park, Bangalore 560066,2Department of Biotechnology and
Bioinformatics, Kuvempu University, Shankarghatta, Karnataka, India,3McKusick-Nathans Institute of Genetic
Medicine and the Departments of Biological Chemistry, Pathology and Oncology, Johns Hopkins University, Baltimore,
Maryland 21205, USA and4Research Unit for Immunoinformatics, Research Center for Allergy and Immunology,
RIKEN Yokohama Institute, Kanagawa, Japan 230-0045
Received on May 11, 2009; revised on July 16, 2009; accepted on July 17, 2009
Advance Access publication July 23, 2009
Associate Editor: Alex Bateman
web application to annotate biological information pertaining to
signaling pathways and to create web-based pathway resources.
PathBuilder enables annotation of molecular events including
protein–protein interactions, enzyme–substrate relationships and
protein translocation events either manually or through automated
importing of data from other databases. Salient features of
PathBuilder include automatic validation of data formats, built-in
modules for visualization of pathways, automated import of data
from other pathway resources, export of data in several standard
data exchange formats and an application programming interface
for retrieving existing pathway datasets.
Availability: PathBuilder is freely available for download at http://
pathbuilder.sourceforge.net/ under the terms of GNU lesser general
public license (LGPL: http://www.gnu.org/copyleft/lesser.html). The
software is platform independent and has been tested on Windows
and Linux platforms.
Supplementary information: Supplementary data are available at
We have developed PathBuilder, an open-source
Experimental research to elucidate biological pathways in detail
has generated large amounts of data that are scattered across the
published literature. Because of the complexity of pathway data,
there is a need for trained biologists to manually collect and curate
biological information. A major issue that needs to be addressed is
to store, retrieve and visualize the collected data in a simple fashion
with provision for integration with other pathway resources.Though
biological pathways (Cerami et al., 2006), there is currently no
publicly available open-source software that allows biologists to
rapidly deploy a web-based pathway resource. The importance of
∗To whom correspondence should be addressed.
Data from external sources
Export of pathway data
(BioPAX / PSI-MI / SBML)
Correlating expression data
for pathway specific signatures
Fig. 1. PathBuilder architecture. Data can be populated manually or
automatically.The stored data can be viewed directly through a web browser
or can be exported to standard exchange formats for visualization and
analysis using other software.
related resources are currently available (Bader et al., 2006).
We have developed PathBuilder, an open-source application
which enables annotation of signaling pathways (Fig. 1).
Biological characteristics of signaling pathways including protein–
protein interactions, enzyme–substrate relationships and protein
translocation events can be catalogued using this software. These
events occur upon stimulation with a specific ligand or activation of
of genes that are transcriptionally regulated by pathways. Thus,
PathBuilder can facilitate pathway data collection as well as rapid
deployment of pathway resources.
PathBuilder is developed using Zope web application framework
(http://www.zope.org/). The data is stored in a MySQL database,
processed in an application layer implemented in Python
programming language and published to the web using DTML, a
Zope HTML templating language.
Data stored in PathBuilder can be accessed via standard web-
based application programming interface (API) which allows third
© The Author 2009. Published by Oxford University Press. All rights reserved. For Permissions, please email: email@example.com
party software to access data, thus enabling interoperability. The
API can be controlled by specifying the URL parameters. For
more information on the use of API, please read the documentation
available on the project web site.
3CREATING AND ANNOTATING PATHWAYS
The annotation pipeline in PathBuilder (Supplementary Fig. 1)
has four central steps—annotation of data, automatic validation
of logical and typographical errors, initial review and review by
Pathway Authorities. The installation of PathBuilder provides an
unpopulated functional database with default parameters. The two
modes of populating PathBuilder include manual entering of data
through a series of web forms and automated import of data.
Currently, PathBuilder successfully imports physical interaction
datasets as PSI-MI (Hermjakob et al., 2004) files from HPRD
(Keshava Prasad et al., 2009), IntAct (Kerrien et al., 2007) and DIP
(Salwinski et al., 2004). This would allow researchers aggregate
data from disparate resources to create custom databases.
PathBuilder was developed primarily for creation of a pathway
resource for which the data was entered manually. There are
separate web forms available for different data types that allow
the user to annotate data through a web browser which permits the
annotation process to be carried out at different geographic locations
Data contained in PathBuilder can be reviewed. Any change
suggested by an initial reviewer is sent automatically to the
respective curator for further changes and the entry is not finalized.
Once the reviewer approves an entry, it is marked as ‘reviewed’and
is finalized in the database. It also allows a final review and editing
by designated scientists who are experts in specific pathways called
‘Pathway Authorities’. The ‘Pathway Authorities’ report errors, if
any, or specify additional information about a pathway that can be
Annotating pathway data
3.2Browse, lookup, display and export of
PathBuilder provides browse and lookup options for the annotated
pathways. The curator or reviewer can lookup using identifiers such
as gene symbol, protein name, Entrez Gene ID or PubMed ID. The
pathway home page contains a brief description, a list of molecules
involved and hyperlinks to view details of downstream signaling
reactions annotated in the pathway. All downstream signaling
reactions are displayed under separate tabs and also allow export
of pathway data (Supplementary Fig. 2).
PathBuilder dynamically generates network graphs that can be
viewed through a web browser using Medusa applet (Hooper and
Bork 2005). PathBuilder also provides pathway data that can be
visualized using downloadable software such as Pajek (Batagelj
1998), Cytoscape (Shannon et al., 2003) and Osprey (Breitkreutz
et al., 2003). Supplementary Figure 3 shows the network graphs of
the IL-1 pathway generated using Medusa, Pajek, Cytoscape and
Dynamic generation of network graphs
3.4Development of NetPath, a resource for human
signaling pathways, using PathBuilder
We used PathBuilder to develop NetPath (http://www.netpath.org/)
as a resource for human signaling pathways (S. Mohan et al.,
submitted for publication). Pathway data were populated manually
using the web forms in PathBuilder. Supplementary Figure 4 shows
various fields for annotating physical interactions. Importantly, the
use of PathBuilder for developing NetPath allowed annotation and
review by experts in different countries, most of whom had no
of various features in PathBuilder with other software available for
pathway annotation such as cPath (Cerami et al., 2006), PATIKA
(Demir et al., 2002), PathCase (Krishnamurthy et al., 2003) and
GenMAPP (Dahlquist et al., 2002).
PathBuilder is a simple software for creation of pathway resources.
PathBuilder facilitates manual entry of biological pathway data
in addition to supporting XML-based import of data from other
publicly available databases. PathBuilder aims to facilitate storage,
retrieval, organization and visualization of biological pathway
data in an efficient manner. Future developments in PathBuilder
will focus on addition of modules that facilitate integration of
transcriptomic data over the current network-based visualization of
We thank the Department of Biotechnology of the Government
of India for research support to the Institute of Bioinformatics,
Bangalore. We would also like to thank Daniel J. Navarro for
providing useful comments on the manuscript.
Funding: National Institute of Health Roadmap Initiative (grant
U54RR020839); National Heart Lung and Blood Institute (contract
Conflict of Interest: none declared.
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