ArticleJournal of the Royal Society, Interface2014
Nonlinear signalling networks and cell-to-cell variability transform external signals into broadly distributed or bimodal responses.
Article in Journal of the Royal Society, Interface, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 17 papers.
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Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
17 citing papers in PubMed, 25 citations in OpenAlex.
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- Modeling Cellular Signaling Variability Based on Single-Cell Data: The TGFβ-SMAD Signaling Pathway.Methods in molecular biology (Clifton, N.J.) · 2023Review
- Differential Expression Analysis of Single-Cell RNA-Seq Data: Current Statistical Approaches and Outstanding Challenges.Entropy (Basel, Switzerland) · 2022Review
- MarcoPolo: a method to discover differentially expressed genes in single-cell RNA-seq data without depending on prior clustering.Nucleic acids research · 2022Article
- ZERO-INFLATED QUANTILE RANK-SCORE BASED TEST (ZIQRANK) WITH APPLICATION TO SCRNA-SEQ DIFFERENTIAL GENE EXPRESSION ANALYSIS.The annals of applied statistics · 2021Article
- Unsupervised machine learning for exploratory data analysis in imaging mass spectrometry.Mass spectrometry reviews · 2020Review
- The dark ventral patch: A bimodal flexible trait related to male competition in red deer.PloS one · 2020Article
- New insights into RAS biology reinvigorate interest in mathematical modeling of RAS signaling.Seminars in cancer biology · 2019Review
- Article
- A new efficient approach to fit stochastic models on the basis of high-throughput experimental data using a model of IRF7 gene expression as case study.BMC systems biology · 2017Article
- Multiplicity of Mathematical Modeling Strategies to Search for Molecular and Cellular Insights into Bacteria Lung Infection.Frontiers in physiology · 2017Review
- A statistical approach for identifying differential distributions in single-cell RNA-seq experiments.Genome biology · 2016Article
- Bistability in the Rac1, PAK, and RhoA Signaling Network Drives Actin Cytoskeleton Dynamics and Cell Motility Switches.Cell systems · 2016Article
- The dynamic control of signal transduction networks in cancer cells.Nature reviews. Cancer · 2015Review
- DYVIPAC: an integrated analysis and visualisation framework to probe multi-dimensional biological networks.Scientific reports · 2015Article
- Species differential regulation of COX2 can be described by an NFκB-dependent logic AND gate.Cellular and molecular life sciences : CMLS · 2015Article
Corrections and comments
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Authors and funding
8 authors at 1 institution in 3 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
We show theoretically and experimentally a mechanism behind the emergence of wide or bimodal protein distributions in biochemical networks with nonlinear input-output characteristics (the dose-response curve) and variability in protein abundance. Large cell-to-cell variation in the nonlinear dose-response characteristics can be beneficial to facilitate two distinct groups of response levels as opposed to a graded response. Under the circumstances that we quantify mathematically, the two distinct responses can coexist within a cellular population, leading to the emergence of a bimodal protein distribution. Using flow cytometry, we demonstrate the appearance of wide distributions in the hypoxia-inducible factor-mediated response network in HCT116 cells. With help of our theoretical framework, we perform a novel calculation of the magnitude of cell-to-cell heterogeneity in the dose-response obtained experimentally.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.