ArticlePLoS computational biology2016
Qualitative Dynamical Modelling Can Formally Explain Mesoderm Specification and Predict Novel Developmental Phenotypes.
Article in PLoS computational biology, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 7 papers.
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
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Who cites it
7 citing papers in PubMed.
- Single-cell transcriptomics illuminates regulatory steps driving anterior-posterior patterning of Drosophila embryonic mesoderm.Cell reports · 2023Article
- Reducing Boolean networks with backward equivalence.BMC bioinformatics · 2023Article
- Thermodynamics-based modeling reveals regulatory effects of indirect transcription factor-DNA binding.iScience · 2022Article
- Behavior-related gene regulatory networks: A new level of organization in the brain.Proceedings of the National Academy of Sciences of the United States of America · 2020Review
- Causal Gene Regulatory Network Modeling and Genomics: Second-Generation Challenges.Journal of computational biology : a journal of computational molecular cell biology · 2019Article
- On the role of sparseness in the evolution of modularity in gene regulatory networks.PLoS computational biology · 2018Article
- Logical Modeling and Analysis of Cellular Regulatory Networks With GINsim 3.0.Frontiers in physiology · 2018Article
Corrections and comments
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Authors and funding
9 authors.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Given the complexity of developmental networks, it is often difficult to predict the effect of genetic perturbations, even within coding genes. Regulatory factors generally have pleiotropic effects, exhibit partially redundant roles, and regulate highly interconnected pathways with ample cross-talk. Here, we delineate a logical model encompassing 48 components and 82 regulatory interactions involved in mesoderm specification during Drosophila development, thereby providing a formal integration of all available genetic information from the literature. The four main tissues derived from mesoderm correspond to alternative stable states. We demonstrate that the model can predict known mutant phenotypes and use it to systematically predict the effects of over 300 new, often non-intuitive, loss- and gain-of-function mutations, and combinations thereof. We further validated several novel predictions experimentally, thereby demonstrating the robustness of model. Logical modelling can thus contribute to formally explain and predict regulatory outcomes underlying cell fate decisions.
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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.