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Predicting Gene Enhancers; Optimising Vaccine Dose and Modelling Wound Healing


Check out our Editors-in-Chief’s selection of papers from the October issue of PLOS Computational Biology.


Prediction of gene regulatory enhancers across species reveals evolutionarily conserved sequence properties

Alterations in gene expression levels are a driving force of both speciation and complex disease. It is therefore of great importance to understand the mechanisms underlying the evolution and function of gene regulatory DNA sequences. Recent studies have revealed that gene expression patterns and transcription factor binding preferences are broadly conserved across diverse animals, but there is extensive turnover in distal gene regulatory regions, called enhancers, between closely related species. Chen and colleagues investigate this seeming incongruence by analysing genome-wide enhancer datasets from six diverse mammalian species.


Fig 2. Fit of model to HPIV infection data at five different inoculum doses.

Exploring the impact of inoculum dose on host immunity and morbidity to inform model-based vaccine design

An important component of vaccines is the amount of pathogen inoculum, dead or alive, that is included in the vaccine. This inoculum dose, sometimes also referred to as antigen dose, needs to be large enough to induce good protective immunity. However, one usually also wants to keep the dose low to reduce costs, maximize the number of vaccine doses available, and minimize potential vaccine side effects. The inoculum dose is currently chosen based on limited data from clinical trials. In this study, Handel and colleagues set up a framework that combines data with mathematical models to illustrate how such a combination could lead to better and more efficient determination of an optimal inoculum dose for vaccines.



Issue Image for October: Quantum chemistry reveals thermodynamic principles of redox biochemistry – Redox reactions define the energetic constraints within which life exists. However, measurements of reduction potentials are scarce and current prediction methods fall short of desired accuracy and coverage. We harness quantum chemistry to enable the high-throughput prediction of reduction potentials with unparalleled accuracy.

Cooperation of dual modes of cell motility promotes epithelial stress relaxation to accelerate wound healing

Many developmental processes involve collective cell motion, driven by migratory behaviours of individual cells and their interactions with the extracellular environment. An outstanding question is how cells regulate their internal driving forces to maintain tissue cohesiveness while promoting the requisite fluidity for collective motion. Progress has been limited by the lack of an integrative framework that couples cellular physical behaviour with stochastic biochemical dynamics underlying cell motion and adhesion. Here Staddon and colleagues develop a cell-based computational model for collective cell migration during epithelial wound repair that integrates tissue mechanics with active cell motility, cell-substrate adhesions, and actomyosin dynamics.


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