Direct Response Analysis in cellular signalling networks

Journal of Theoretical Biology
N ShayeghiA C C Coolen

Abstract

Direct Response Analysis is a general computational tool for quantifying direct functional interactions between components in cellular signalling systems from experimental perturbations and measurements alone. This paper aims to reveal the biological meaning of the direct response coefficients obtained upon applying DRA to simple Michaelis-Menten type proteomic and gene regulatory systems. These systems describe dimer formation and dissociation, protein preduction and decay, and transcription. We derive explicit formulae for the direct response coefficients in terms of biochemical reaction rates, and clarify the potential and limitations of the DRA method. We find that response coefficients are strongly asymmetric, and that they balance persistent characteristics of reactions (e.g. the ratios of on- and off rates) against the time-scales over which these reactions act; fast reactions give stronger response coefficients. The direct interactions between protein species, caused by dimer formation, are effectively negative. We illustrate our results with numerical simulations.

References

Nov 30, 2004·Biology of the Cell·Athel Cornish-BowdenFlavio Guíñez Abarzúa
May 20, 2006·Science·Christopher T WorkmanTrey Ideker
Oct 25, 2006·Nature Cell Biology·Bree B AldridgePeter K Sorger
Mar 3, 2007·Nature Cell Biology·Boris N Kholodenko

❮ Previous
Next ❯

Related Concepts

Trending Feeds

COVID-19

Coronaviruses encompass a large family of viruses that cause the common cold as well as more serious diseases, such as the ongoing outbreak of coronavirus disease 2019 (COVID-19; formally known as 2019-nCoV). Coronaviruses can spread from animals to humans; symptoms include fever, cough, shortness of breath, and breathing difficulties; in more severe cases, infection can lead to death. This feed covers recent research on COVID-19.

Blastomycosis

Blastomycosis fungal infections spread through inhaling Blastomyces dermatitidis spores. Discover the latest research on blastomycosis fungal infections here.

Nuclear Pore Complex in ALS/FTD

Alterations in nucleocytoplasmic transport, controlled by the nuclear pore complex, may be involved in the pathomechanism underlying multiple neurodegenerative diseases including Amyotrophic Lateral Sclerosis and Frontotemporal Dementia. Here is the latest research on the nuclear pore complex in ALS and FTD.

Applications of Molecular Barcoding

The concept of molecular barcoding is that each original DNA or RNA molecule is attached to a unique sequence barcode. Sequence reads having different barcodes represent different original molecules, while sequence reads having the same barcode are results of PCR duplication from one original molecule. Discover the latest research on molecular barcoding here.

Chronic Fatigue Syndrome

Chronic fatigue syndrome is a disease characterized by unexplained disabling fatigue; the pathology of which is incompletely understood. Discover the latest research on chronic fatigue syndrome here.

Evolution of Pluripotency

Pluripotency refers to the ability of a cell to develop into three primary germ cell layers of the embryo. This feed focuses on the mechanisms that underlie the evolution of pluripotency. Here is the latest research.

Position Effect Variegation

Position Effect Variagation occurs when a gene is inactivated due to its positioning near heterochromatic regions within a chromosome. Discover the latest research on Position Effect Variagation here.

STING Receptor Agonists

Stimulator of IFN genes (STING) are a group of transmembrane proteins that are involved in the induction of type I interferon that is important in the innate immune response. The stimulation of STING has been an active area of research in the treatment of cancer and infectious diseases. Here is the latest research on STING receptor agonists.

Microbicide

Microbicides are products that can be applied to vaginal or rectal mucosal surfaces with the goal of preventing, or at least significantly reducing, the transmission of sexually transmitted infections. Here is the latest research on microbicides.