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Ferreira Ramos, A.

Publications and source records attributed to Ferreira Ramos, A..

4 recordsLinked to original sources

Comment on "Solving the time-dependent protein distributions for autoregulated bursty gene expression using spectral decomposition"

The authors of the commented article claim that the exact time-dependent solutions of the stochastic model for a self-repressing gene previously obtained by us are both "incomplete and incorrect" because their calculations issued complex numbers as decaying rates of the system to steady state. We show that the imaginary decaying rates result from a methodological artifact. We use a linear algebraic approach to show that the decaying rates are those reported in [ Exact time-dependent solutions for a self-regulating gene. Phys. Rev. E 83: 062902 (2011)]. Thus, our solution is both complete and correct. Additionally, the authors claim that they have discovered a new class of operator having complex eigenvalues and non-orthogonal eigenfunctions. We show that the operator can actually be written in the usual self-adjoint form, and, hence, it has real eigenvalues and orthogonal eigenfunctions.

systems biology↗

Bursty expression enhances reliability of messaging in gene networks

The promoter state of a gene and its expression levels are modulated by the amounts of transcription factors interacting with its regulatory regions. Hence, one may interpret a gene network as a communicating system in which the state of the promoter of a gene (the source) is communicated by the amounts of transcription factors that it expresses (the message) to modulate the state of the promoter and expression levels of another gene (the receptor). The reliability of the gene network dynamics can be quantified by the Shannons entropy of the message and the mutual information between the message and the promoter state. Here we consider a stochastic model for a binary gene and use its exact steady state solutions to calculate the entropy and mutual information. We show that a slow switching promoter having long and equally standing ON and OFF states maximizes the mutual information and reduces entropy. That is a bursty regime generating a high variance message governed by a bimodal probability distribution with peaks of the same height. Our results indicate that Shannons theory can be a powerful framework for understanding how bursty gene expression conciliates with the striking spatio-temporal precision exhibited in pattern formation of developing organisms.

systems biology↗

Some lessons and perspectives for applications of stochastic models in biological and cancer research

Randomness is an unavoidable feature of inner cellular environment and its effects propagate to higher levels of living matter organization such as cells, tissues, and organisms. Approaching those systems experimentally to understand their dynamics is a complex task because of the plethora of compounds interacting in a web that combines intra and inter level elements such that a coordinate behavior come up. Such a characteristic points to the necessity of establishing principles that help on the description, categorization, classification, and the prediction of the behavior of biological systems. The theoretical machinery already available, or the ones to be discovered motivated by biological problems, can play an important role on that quest. Here we exemplify the applicability of theoretical tools by discussing some biological problems that we have approached mathematically: fluctuations in gene expression and cell proliferation in the context of loss of contact inhibition. We discuss the methods that we have employed aiming to provide the reader with a phenomenological, biologically motivated, perspective of the use of theoretical methods. Furthermore, we discuss some of our conclusions after employing our approach and some research perspectives that they motivate.

systems biology↗

Bursting on a two states stochastic model for gene transcription in Drosophila embryos

Recent experimental data on the transcription dynamics of eve gene stripe two formation of Drosophila melanogaster embryos occurs in bursts of multiple sizes and durations. That has motivated the proposition of a transcription model having multiple ON states for the promoter of the eve gene each of them characterized by different synthesis rate. To understand the role of multiple ON states on gene transcription we approach the exact solutions for a two state stochastic model for gene transcription in D. melanogaster embryos and derive its bursting limit. Simulations based on the Gillespie algorithm at the bursting limit show the occurrence of bursts of multiple sizes and durations. Based on our theoretical approach, we interpret the aforementioned experimental data as a demonstration of the intrinsic stochasticity of the transcriptional processes in fruit fly embryos. Then, we conceive the experimental arrangement to determine when gene transcription has multiple ON promoter state in a noisy environment.

developmental biology↗