Computational and Systems Biology

eLife assessment

The study presents a valuable tool for searching molecular dynamics simulation data, making such data sets accessible for open science. The authors provide convincing evidence that it is possible to identify useful molecular dynamics simulation data sets and their analysis can produce valuable information.

eLife assessment

This fundamental study provides a unique tool for assessing the range of phosphorylation in insulin reactions due to genetic variation and dietary influence through the utilization of genetically distinct mouse strains. The discoveries of this study hold substantial importance, as they shed light on the interplay between genetic attributes and environmental conditions in shaping the insulin-signaling network within skeletal muscle, a crucial regulator of metabolism. The supporting evidence presented is compelling, and the work is anticipated to captivate a wide audience within the metabolism discipline due to its extensive appeal and by providing inspiration for further hypothesis-driven research.

eLife assessment

The authors have made important contributions to our understanding of the pathogenesis of erectile dysfunction (ED) in diabetic patients. They have identified the gene Lbh, expressed in pericytes of the penis and decreased in diabetic animals. Overexpression of Lbh appears to counteract ED in these animals. The authors also confirm Lbh as a potential marker in cavernous tissues in both humans and mice. While solid evidence supports Lbh's functional role as a marker gene, further research is needed to elucidate the specific mechanisms by which it exerts its effects. This work is of interest to those working in the fields of ED and angiogenesis.

eLife assessment

This important study deepens our understanding of macrophage phenotypes in pathological contexts and identifies a new macrophage state associated with tissue fibrosis, as well as putative drivers of this cellular state. The authors provide convincing evidence and performed a well-thought-out and thoroughly described computational analysis of single-cell RNA-sequencing data. This work will be of broad interest to the fields of tissue inflammation, fibrosis, macrophage biology, and immunology.

eLife assessment

This valuable study presents a screening pipeline (SPICE) for detecting DNA motif spacing preferences between TF partners. SPICE predicts previously known composite elements, but experiments to elucidate the nature of the predicted novel interaction between JUN and IKZF1 are incomplete. These experiments would benefit from more rigorous approaches using other databases to explore additional relevant data. The work will be of broad interest to those involved in dissecting the regulatory logic of mammalian enhancers and promoters.

eLife assessment

This valuable study reports a new method based on batch active learning to optimize the biological and pharmaceutical properties of small molecules of pharmaceutical interest. The new method seems compelling, but the theoretical analysis is incomplete and the reproducibility and impact of the article would benefit from disclosing the code and datasets used in the study. With these aspects strengthened, this paper would be of interest to computational and medicinal chemists and scientists working in the drug discovery field.

eLife assessment

This important study makes a bold step towards understanding what fraction of DNA that is liberated from different tissues in a healthy human is found in circulation as cell-free DNA. Unfortunately, the evidence for the conclusions is presently incomplete, but with additional controls, this could become a major achievement for reference in understanding changes in cell-free DNA in disease states.

eLife assessment

This valuable paper describes a web-based tool for curated association mapping results from the Drosophila genome reference panel. With this tool, one can visualize and view association results for various phenotypes, and the authors provide examples for the use of the resource, including study summary statistics. The evidence for the tool working as advertised is solid, but further improvements to the tool would increase its value for the community.

eLife assessment

This valuable study uses adult and neonatal murine models, together with genetic approaches, to propose that vitamin D, via Ikfz3/Aiolos, suppresses IL-2 signalling and reduces IL-2 signalling in Th2 cells. While vitamin D has been previously thought to modulate both effector and regulatory T-cell populations via the control of IL-2 signalling, this study provides solid new data of interest to immunologists as well as asthma researchers.

eLife assessment

This study provides a valuable computational tool for analyzing and deconvoluting a pool of plasmids sequenced without barcoding using nanopore long-read sequencing. While the authors provide convincing validation, this tool might still present limitations concerning practical applications. The work will be of interest to researchers in need of rapid and cost-effective verification of plasmid sequences.

eLife assessment

This valuable study describes the development of a new structure-based learning approach to predict transcription binding specificity and its application in the modeling of regulatory complexes in cis-regulatory modules. The authors developed a structure-based learning approach to predict TF binding features and model the regulatory complex(es) in cis-regulatory modules, integrating experimental knowledge of structures of TF-DNA complexes and high-throughput TF-DNA interactions. The validation presented by the authors is currently incomplete, with a large variability in the performance of the method on the different TF families tested.

eLife assessment

The work introduces two valuable concepts in antimicrobial resistance: "variant vulnerability" and "drug applicability", which can broaden our ways of thinking about microbial infections through evolution-based metrics. The authors present a compelling analysis of a published dataset to illustrate how informative these metrics can be, study is still incomplete, as only a subset of a single dataset on a single class of antibiotics was analyzed. Analyzing more datasets, with other antibiotic classes and resistance mutations, and performing additional theoretical simulations could demonstrate the general applicability of the new concepts.

eLife assessment

In this potentially useful study, the authors use deep learning models to provide solid evidence that epithelial wounding triggers bursts of cell division at a characteristic distance away from the wound. The usefulness of the methods to the community will depend on documenting their robustness toward variability in temporal resolution and/or mitotic event duration and demonstrating their overall superiority over existing approaches.

eLife assessment

This study provides important, detailed insights into the early stages of angiogenesis and points towards a novel mechanism that could be used to control the density and location of developing blood vessels. Convincing experimental methods, analysis techniques, and mathematical modeling are used to systematically support the findings. This study of the mechanisms by which paracrine and juxtacrine cues control the formation of new blood vessels will be of broad interest to colleagues studying angiogenesis and blood vessel formation.

eLife assessment

In this important study, authors have integrated genetic and genomic datasets from humans and mice to unveil shared networks and pathways associated with coronary artery disease. Their compelling analysis has led to the identification of novel regulatory genes and pathways in vascular tissues and in the liver, allowing for a more in-depth understanding of CAD pathogenesis.

eLife assessment

This study provides a useful catalog of the cardiac proteome and transcriptome in response to intermittent fasting. Although mechanistic integration is limited, the technical aspects have been executed in a solid way, and sufficient evidence is provided to support the main conclusions. Future work can build on this study to expand our understanding of the relationship between dietary perturbations and cardiac function.

eLife assessment

This study presents a comprehensive benchmarking approach, reviewing existing cell-type deconvolution methods in spatial transcriptomics. The authors not only assess these methods across various datasets but also successfully establish a reliable framework for their evaluation, notably highlighting RCTD and Cell2location for their performance. By implementing a full Nextflow pipeline, Docker containers, and a rigorous assessment of the simulator, this work offers robust insights that elevate the standards for future evaluations and provides a resource for those seeking to improve or develop new deconvolution methods. The thorough comparison and analysis of methods, coupled with a strong emphasis on reproducibility, provide solid support for the findings.

eLife assessment

This article describes a useful python-based image-analysis tool for bacteria growing in the 'mother-machine' microfluidic device. This new method for image segmentation and tracking offers a user-friendly graphical interface based on the previously developed, promising environment for image analysis 'Napari'. The authors demonstrate the usefulness of their software and its robust performance by comparing it to other methods used for the same purpose. The comparison provides solid support for the new method, although it would have been even stronger if tested using data sets from other groups. This article will be of interest for scientists who utilize the 'mother machine', not least because it also provides a short overview of how to set up this widely used device.

eLife assessment

This study provides valuable insights into the dynamic interplay between the starvation and hyper-osmotic stress responses in budding yeast, where the presence of one stress can impact the concurrent effects of another perturbation. Using microfluidic devices and extensive quantitative analyses of time-series responses, the authors applied concurrent (in-phase) or alternate (anti-phase) stresses. Their compelling analyses reveal some unexpected behaviors that could not have been guessed from simpler experimental designs, revealing that investigating complex environmental inputs can reveal new biological insights, even for well-studied systems.

eLife assessment

The adaptation of organs including the heart to chronic stress has interested biologists for a long time. Using an elegant model of overexpression of adenyly cyclase, the authors demonstrate posttranslational modification of the protein by phosphorylation, making an important contribution to approaches for the protection of heart performance in these transgenic mice. The convincing results open a new paradigm in understanding the biological effects of stress.