SHARP Pathway
Database
Institut
Curie node:
Coordinator: Patrick Poullet.
Participants: Amélie Gelay, Andrei Zinovyev, Philippe La Rosa and Emmanuel Barillot.
Collaborators: François Radvanyi, Olivier Delattre, Yohanns Bellaiche and Jean
de-Gunzburg.
SHARP global coordinator: Ron Shamir (School of Computer
Science, Tel Aviv University, Israel).
The SHARP project:
Making sense of the intricate network
of proteins and genes regulations that take place inside the cell during cell
growth, differentiation and apoptosis is a critical step in understanding how
these processes are controlled at the molecular level. Unfortunately, the
biological knowledge collected so far is fragmented in thousands of research
articles of heterogeneous quality making it difficult for researchers to
comprehend globally the mechanisms involved. This knowledge must be centralized
and standardized to become easily accessible. Furthermore, as the data
accumulate, it becomes necessary to use computer power to store, visualize
and analyze these complex regulations.
The SHARP consortium was initiated
by Ron Shamir at Tel Aviv University to address this problem using a
collaborative approach. Researchers from all around the world -including from
the Institut Curie- have already joined this consortium. The goal of this
global collaboration is to take advantage of each research group’s expertise on
specific signaling pathways to collect, curate and formalize the data available
from the literature or from their own laboratories. New data are regularly
integrated to a central pathway database and made available to all members of
the consortium (see figure below).
A SHARP software was designed
and developed by Ron Shamir’s group to assist researchers through this task.
This tool consists of a multi-platform (java-based) intuitive pathway
visualization module which communicates with an underlying database. The user
can use this interface to submit new data and to query, edit and analyze the
data stored. This tool can also be used to superimposed external quantitative
data such as gene expression data (microarrays) over the signaling
pathways.
Our task is to provide technical
support to the research groups of the Institut Curie involved in the SHARP
project and to coordinate their work with that of the other members of the
consortium. The data collected are then used in other projects of the Group
in particular for the analysis of microarray data
(e.g. Kernelchip).
The Retinoblastoma (RB) Pathway case:
Participants: Amélie Gelay, François Radvanyi,
Andrei Zinovyev, Emmanuel Barillot.
The purpose of the present work is
to collect as much information as possible on gene-regulatory networks and
organize it in an exploitable way for the analysis of data from microarrays. We
started with RB, a tumor suppressor gene involved in a pathway controlling the
cell cycle progression, which is one of the most frequent targets of genetic
alterations in human cancer.
The data are collected from public
sources (reviews, publications…) and stored using CellDesigner. CellDesigner is
a structured diagram editor for drawing gene-regulatory and biochemical
networks. These networks are drawn based on the process diagram, with the
graphical notation system proposed by Kitano, and are stored using the Systems
Biology Markup Language (SBML). SBML is a standard computer-readable format for
representing models of biochemical reaction networks. It is applicable to
metabolic networks, cell-signaling pathways, regulatory networks, and many
others. Once converted in SBML format, signaling pathway data can be imported
in network visualization tools such as SHARP.
References for CellDesigner:
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