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BITS2007 Meeting
BITS2007 Meeting



26-28 April 2007 Napoli, Italy

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Identification of Perturbed Pathways Using High-throughput Data
 
Motivation
Cells live in a dynamic environment in which they encounter various perturbations.
These perturbations may arise from toxic compounds, environmental changes, mutations,
or a disease. Identifying the molecules and cellular pathways that are affected can
reveal the nature of a perturbation, provide potential therapeutic targets and shed
light on mechanisms of cellular adaptation. We present a computational method to
discover the pathways that are altered by a perturbation by analyzing high-throughput
data in Saccharomyces cerevisiae.

Methods
Our method combines different types of high-throughput data to develop a coherent,
mechanistic view of how cellular pathways are alterated. We have created a graphical
model of the interactome based on physical data. The model also incorporates
relations between genes and the proteins that regulate them, using a genome-wide map
of experimentally determined transcriptional regulatory sites. We developed a novel
algorithm to search for the pathways that are altered by the perturbation.

Results
We assess our method by applying it to over 100 datasets where the perturbations are
known single gene deletions. In these test data, the genes and pathways identified by
the algorithm are relevant to the actual perturbation in 80% of the 104 cases.
We use the same algorithm to predict the pathways that are most affected by different
compounds. We identify genes known to be responsive to the agents and affected
paythways that are in agreement with biological findings.
 
Id: 106
Place: Napoli, Italy
Centro Congressi "Federico II"
Via Partenope 36
Napoli
Starting date:
28-Apr-2007   09:00
Duration: 20'
Contribution type: Oral
Primary Authors: RIVA, Laura (MIT Biological Engineering Division, Cambridge, USA; Department of Biomedical Engineering, Polytechnic University of Milan, Milano)
Co-Authors: YEGER-LOTEM, Esti (MIT Biological Engineering Division, Cambridge, USA; Whitehead Institute for Biomedical Research, Cambridge, USA)
KARGER DAVID, R (Computer Science and Artificial Intelligence Laboratory,MIT, Cambridge, USA)
PATTINI, Linda (Department of Biomedical Engineering, Polytechnic University of Milan, Milano)
CASARI, Giorgio (Human Molecular Genetics Unit, San Raffaele Scientific Institute, Milano)
CERUTTI, Sergio (Department of Biomedical Engineering, Polytechnic University of Milan, Milano)
FRAENKEL, Ernest (MIT Biological Engineering Division, Cambridge, USA; Computer Science and Artificial Intelligence Laboratory,MIT, Cambridge, USA)
Presenters: RIVA, Laura
 
Included in session: Session 6: Gene expression and system biology
Included in track: Gene expression and system biology
 




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