Computational and Systems Biology

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

The effect of Vitamin D supplementation in reducing asthma via anti-inflammatory mechanisms is a topic of wide interest, with somewhat conflicting published data. Here, bioinformatic approaches help to identify a role of VDR in inducing the expression of the key regulator Ikzf3, which possibly suppresses the IL-2/STAT5 axis, consequently blunting the Th2 response and mitigating allergic airway inflammation. These are important findings based on convincing evidence.

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

This manuscript introduces two valuable new metrics - "variant vulnerability" and "drug applicability" - that would be of use to identify candidate drugs for treating infections while considering longer-term, evolution-based treatment outcomes. Despite the intuitive appeal of the metrics and their potential, the study remains incomplete, as it fails to demonstrate the generality of the approach. The work could be improved by analysing a broader range of data in a systematic way and directly tying the metrics to outcomes, which would make it possible to better assess their impact and utility.

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, demonstrating their overall superiority over existing approaches and making the code possible to use by others.

eLife assessment

The authors used an appropriate micro-engineered experimental model of angiogenesis coupled to mathematical model to study the early steps of the angiogenic sprouting. To this end, the authors developed a convincing model to predict how VEGF activates Delta-Notch signaling. The work affords important new insight into the complex processes involved in the onset of angiogenesis.

eLife assessment

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

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 makes a valuable contribution to spatial transcriptomics by rigorously benchmarking cell-type deconvolution methods, assessing their performance across diverse datasets with a focus on biologically relevant, previously unconsidered aspects. The authors demonstrate the strengths of RCTD, cell2location, and SpatialDWLS for their performance, while also revealing the limitations of many methods when compared to simpler baselines. 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 provides a review and test of image-analysis methods for bacteria growing in the 'mother-machine' microfluidic device, introducing also a new graphical user interface for the computational analysis of mother-machine movies based on the 'Napari' environment. The tool allows users to segment cells based on two previously published methods (classical image transformation and thresholding as well as UNet-based analysis), with solid evidence for their robust performance based on comparison with other methods and use of datasets from other labs. While it was difficult to assess the user-friendliness of the new GUI, it appears to be valuable and promising for the field.

eLife assessment

This study presents important findings on how cells sense and respond to their surroundings, in particular when two environmental signals are presented periodically, in alternation or conjunction. The compelling analyses reveal some unexpected behaviors that could not have been drawn, from simpler experimental designs, related to the dynamic interplay between the starvation and hyper-osmotic stress responses in budding yeast, exemplifying that applying complex signals can unveil new biological insights, even for well-studied systems. The work will be of broad interest to researchers interested in fungal biology, dynamic systems, cell signaling, and cell biology.

eLife assessment

This study describes important results from cardiac-specific overexpression of adenylyl cyclase type 8 (TGAC8) mice that was integrated with transcriptomic and proteomic evidence. The paper convincingly provides new insights into how one can interpret signals from visceral organs.

eLife assessment

This study provides an important tool for predicting binding between immune cells receptors and antigens based on protein sequence data. The analysis convincingly showed the tool's effectiveness in both supervised TCR binding prediction and unsupervised clustering, surpassing existing methods in accuracy and reducing annotation costs. This study will be of interest to immunologists and computational biologists.

eLife assessment

This valuable study aims to identify pioneer transcription factors, which are defined as transcription factors that compete with nucleosomes for DNA binding. The authors provide methods for identifying pioneer transcription factors on a cell type basis, using nucleosome positioning and motif information across different cell lines. The evidence to support the claims is largely solid. This work will be of interest to computational and molecular biologists working on transcription factors.

eLife assessment

This valuable work presents new results to characterize the relationship between electrical excitation and torque generation in stick insect joints. The evidence supporting this work is a series of torque-voltage measurements across individuals. The strength of evidence is solid in supporting the outcomes, but some details of the methodology, which could potentially shed light on the sources of this variation, are missing.

eLife assessment

This study presents a valuable description of RNA in extracellular vesicles (EV-RNAs) and highlights the potential to develop biomarkers for the early detection of colorectal cancer (CRC) and precancerous adenoma (AA). The data were analysed using solid methodology and would benefit from further validation at each stage of CRC/AA to evaluate the potential application to early detection of CRC and AA.

eLife assessment:

This important study describes spatial RNA processing events by combining methods for single-cell transcriptomics data with spatial transcriptomics data. The evidence supporting the claims of the authors is solid, although the analysis could be further strengthened by including a broader range of samples as well as orthogonal validation either by experimental methods or simulated data. The work will be of general interest to researchers in the spatial transcriptomics field as well as researchers investigating alternative pre-mRNA processing across diverse tissues.

eLife assessment

This paper describes an important, well-organized study into an under-exploited area of spatial transcriptomics. The limitations of the approach are generally made clear, but there is insufficient orthogonal validation to demonstrate the biological significance of the results, which leads to the evidence for the claims being currently incomplete. Nevertheless, the tools presented will provide a resource to researchers wishing to characterise spatial patterning of mRNAs, and the paper will be of interest to researchers studying cell biology, RNA biology, and method development for spatial transcriptomics/proteomics.

eLife assessment

This important study combines virology experiments and mathematical modeling to determine the nuclear export rate of each of the eight RNA segments of the influenza A virus, leading to the proposal that a specific retention of mRNA within the nucleus delays the expression of antigenic viral proteins. The proposed model for explaining the differential rate of export is compelling, going beyond the state of the art, but the experimental setup is incomplete and would benefit from additional approaches. The insight so far is interesting, but because in the end it is left as an observation, the overall advance remains limited.