Systems Biology

eLife Assessment

This valuable study uses dynamic metabolic models to compare perturbation responses in a bacterial system, analyzing whether they return to their steady state or amplify beyond the initial perturbation. The evidence supporting the emergent properties of perturbed metabolic systems to network topology and sensitivity to specific metabolites is solid, although the authors do not explain the origin of some significant inconsistencies between models.

Editors Assessment:

PhysiCell is an open source multicellular systems simulator for studying many interacting cells in dynamic tissue microenvironments. As part of the PhysiCell ecosystem of tools and modules this paper presents a PhysiCell addon, PhysiMeSS (MicroEnvironment Structures Simulation) which allows the user to accurately represent the extracellular matrix (ECM) as a network of fibres. This can specify rod-shaped microenvironment elements such as the matrix fibres (e.g. collagen) of the ECM, allowing the PhysiCell user the ability to investigate physical interactions with cells and other fibres. Reviewers asked for additional clarification on a number of features. And the paper now clear future releases will provide full 3D compatibility and include working on fibrogenesis, i.e. the creation of new ECM fibres by cells.

This evaluation refers to version 1 of the preprint

eLife Assessment

This manuscript presents a valuable new quantitative crosslinking mass spectrometry approach using novel isobaric crosslinkers. The data are solid and the method has potential for a broad application in structural biology if more isobaric crosslinking channels are available and the quantitative information of the approach is exploited in more depth.

eLife Assessment

This valuable study significantly enhances our understanding of how various ligands and receptors interact within the Notch signaling pathway. By developing novel cell-based assay systems, the authors systematically analyzed the effects of different ligand-receptor combinations on pathway activation. The convincing data reveal intriguing and unexpected differences and provide a foundation for interpreting Notch signalling in both normal and disease-related contexts.

eLife Assessment

This interesting study focuses on a previously reported positive correlation between translational efficiency and protein noise. This is unexpected as typically noise is inversely related to expression and increasing translation efficiency would increase the protein expression and thus be expected to reduce noise in gene expression. Using mathematical modeling and analysis of experimental data the authors argue that this phenomenon arises due to ribosomal demand. However, the work appears incomplete, with the reviewers having raised questions regarding the validity of the assumptions used in the mathematical model as well as the clarity of the presentation.

eLife Assessment

This study reports differences in proteomic profiles of embryonic versus induced pluripotent stem cells. This important finding cautions against the interchangeable use of both types of cells in biomedical research, although the mechanisms responsible for these differences remains unknown. The proteomic evidence is convincing, even though there is limited validation with other methods.

eLife Assessment

Genetic analysis of complex traits in Drosophila provides a resource for exploring the relationship between genetic and phenotypic variation. The web tool DGRPool presented in this paper makes data and results from the Drosophila Genetic Reference Panel accessible that will enable downstream analyses of genetic association. The findings of this paper are considered to be important, with practical implications beyond a single subfield, supported by convincing evidence using appropriate and validated methodology in line with current state of the art.

eLife assessment

This important study provides a comprehensive assessment of mitochondrial function across age and sex in mice. The strength of evidence supporting this resource is compelling, given the exhaustive number of tissues profiled and in-depth analyses performed.

eLife assessment:

This theoretical study makes a useful contribution to our understanding of a subtype of type 2 diabetes – ketosis-prone diabetes mellitus (KPD) – with a potential impact on our broader understanding of diabetes and glucose regulation. The article presents an ordinary differential equation-based model for KPD that incorporates a number of distinct timescales – fast, slow, as well as intermediate, incorporating a key hypothesis of reversible beta cell deactivation. The presented evidence is solid and shows that observed clinical disease trajectories may be explained by a simple mathematical model in a particular parameter regime.

eLife assessment

This study presents a fundamental finding on how levels of m6A levels are controlled, invoking a consolidated model where degradation of modified RNAs in the cytoplasm plays a primary role in shaping m6A patterns and dynamics, rather than needing active regulation by m6A erasers and other related processes. The evidence is compelling and uses transcriptome-wide data and mechanistic modeling. However, it is possible that m6A-erasers will have roles in specific developmental contexts or conditions, so this model may not apply universally.