BACK TO INDEX
Publications of Eduardo D. Sontag jointly with S. Prabakaran
Articles in journal or book chapters
and E.D. Sontag.
Paradoxical results in perturbation-based signaling network reconstruction.
Keyword(s): MAPK cascades,
gene and protein networks,
This paper describes a potential pitfall of perturbation-based approaches to network inference It is shows experimentally, and then explained mathematically, how even in the simplest signaling systems, perturbation methods may lead to paradoxical conclusions: for any given pair of two components X and Y, and depending upon the specific intervention on Y, either an activation or a repression of X could be inferred. The experiments are performed in an in vitro minimal system, thus isolating the effect and showing that it cannot be explained by feedbacks due to unknown intermediates; this system utilizes proteins from a pathway in mammalian (and other eukaryotic) cells that play a central role in proliferation, gene expression, differentiation, mitosis, cell survival, and apoptosis and is a perturbation target of contemporary therapies for various types of cancers. The results show that the simplistic view of intracellular signaling networks being made up of activation and repression links is seriously misleading, and call for a fundamental rethinking of signaling network analysis and inference methods.
BACK TO INDEX
This material is presented to ensure timely dissemination of
scholarly and technical work. Copyright and all rights therein
are retained by authors or by other copyright holders.
Last modified: Sun Feb 13 12:55:49 2022
This document was translated from BibTEX by