eLife

Latest preprint reviews

1. An interpretable neural network unveils higher-order epistasis in large protein sequence-function relationships

   This article has 2 authors:

   1. Palash Sethi
   2. Juannan Zhou

   This article has been curated by 1 group:

   • Curated by eLife

     eLife Assessment

     In this important work, the authors present a new transformer-based neural network designed to isolate and quantify higher-order epistasis in protein sequences. They provide solid evidence that higher-order epistasis can play key roles in protein function. This work will be of interest to the communities interested in modeling biological sequence data and understanding mutational effects.

   Reviewed by eLife

2. Ω-Loop mutations control dynamics of the active site by modulating the hydrogen-bonding network in PDC-3 β-lactamase

   This article has 6 authors:

   1. Shuang Chen
   2. Andrew R Mack
   3. Andrea M Hujer
   4. Christopher R Bethel
   5. Robert A Bonomo
   6. Shozeb Haider

   This article has been curated by 1 group:

   • Curated by eLife

     eLife Assessment

     This manuscript uses adaptive-bandit simulations to describe the dynamics of the Pseudomonas-derived chephalosporinase PDC-3 β-lactamase and its mutants to better understand antibiotic resistance. The finding, that clinically observed mutations alter the flexibility of the Ω- and R2-loops, reshaping the cavity of the active site, is valuable to the field. The evidence is considered incomplete, however, with the need for analysis to demonstrate equilibrium weighting of adaptive trajectories and related measures of statistical significance.

   Reviewed by eLife

3. Product-stabilized filamentation by human glutamine synthetase allosterically tunes metabolic activity

   This article has 12 authors:

   1. Eric Greene
   2. Richard Muniz
   3. Hiroki Yamamura
   4. Samuel E Hoff
   5. Priyanka Bajaj
   6. D John Lee
   7. Erin M Thompson
   8. Angelika Arada
   9. Gyun Min Lee
   10. Massimiliano Bonomi
   11. Justin M Kollman
   12. James S Fraser

   This article has been curated by 1 group:

   • Curated by eLife

     eLife Assessment

     This manuscript employs cryo-EM, mutational analysis, and biochemical assays to explore the molecular basis by which glutamine promotes filamentation and regulates the activity of human glutamine synthetase (hGS) by stabilizing interactions between hGS decamers. The studies supporting this mechanism are solid, but could be improved by providing more clarity and by addressing methodological issues in the cryoEM data processing workflow. This work will be of particular interest and useful to groups interested in understanding the molecular basis of nutrient sensing, cellular metabolism, and structural regulation of enzyme activity.

   Reviewed by eLife

4. Heterozygote advantage cannot explain MHC diversity, but MHC diversity can explain heterozygote advantage

   This article has 1 author:

   1. Joshua L Cherry

   This article has been curated by 1 group:

   • Curated by eLife

     eLife Assessment

     This valuable study re-evaluates a published simulation model on the role of heterozygote advantage in shaping MHC diversity. By modifying key modeling assumptions, the author argues that the original conclusions depend on a narrow and potentially unrealistic parameter range. While the work is in principle solid, the robustness of this claim is viewed differently by the reviewers. The manuscript further proposes an alternative modeling framework in which expansion of the MHC gene family allows homozygotes to outperform heterozygotes, thereby challenging the idea that heterozygote advantage alone can account for high allelic diversity at MHC loci. The topic is highly relevant for eco-immunology and evolutionary genetics, although a clearer delineation of the model's scope would help readers assess its broader implications.

   Reviewed by eLife

5. Starvation transforms signal encoding in C. elegans thermoresponsive neurons and suppresses heat avoidance via bidirectional glutamatergic and peptidergic signaling

   This article has 2 authors:

   1. Saurabh Thapliyal
   2. Dominique A Glauser

   This article has been curated by 1 group:

   • Curated by eLife

     eLife Assessment

     This important study shows how hunger alters avoidance of harmful heat in C. elegans by reconfiguring the activity of key sensory neurons. The evidence is convincing, with well-designed behavioural, genetic, and imaging experiments that support the main conclusions. The work will be of interest to neuroscientists studying how internal states shape sensory processing and behaviour across species.

   Reviewed by eLife

6. Nucleation-dependent propagation of Polycomb modifications emerges during the Drosophila maternal to zygotic transition

   This article has 5 authors:

   1. Natalie Gonzaga-Saavedra
   2. Eleanor A Degen
   3. Isabella V Soluri
   4. Corinne Croslyn
   5. Shelby A Blythe

   This article has been curated by 1 group:

   • Curated by eLife

     eLife Assessment

     This study employed state-of-the-art quantitative imaging and genomics approaches to address a fundamental question regarding the establishment of Polycomb domains during Drosophila embryogenesis. The critical developmental stage was pinpointed to the maternal-to-zygotic transition, rather than earlier stages, providing clarification for the field. The roles of two factors, Zelda and GAGA-factor, were investigated, which reveal that Zelda, but not GAGA-factor, contributes to this process. These compelling findings have implications for chromatin and developmental biology.

   Reviewed by eLife

7. Synaptotagmin 1 and Synaptotagmin 7 promote MR1-mediated presentation of Mycobacterium tuberculosis antigens

   This article has 7 authors:

   1. Se-Jin Kim
   2. Jessie C Peterson
   3. Andrew J Olive
   4. Fikadu G Tafesse
   5. Corinna A Kulicke
   6. Elham Karamooz
   7. David Lewinsohn

   This article has been curated by 1 group:

   • Curated by eLife

     eLife Assessment

     This useful study examines the contribution of synaptotagmin 1 and synaptotagmin 7 to metabolite antigen presentation to mucosal-associated invariant T (MAIT) cells; it begins to address a critical gap in our understanding of the antigen presentation mechanisms of these cells. Strengths of the study include the use of Mtb to study the dynamics of antigen presentation to MAIT cells instead of a synthetic antigen. The strength of the evidence to support the conclusion is solid.

   Reviewed by eLife

8. Macroscopic Analyses of RNA-Seq Data to Reveal Chromatin Modifications in Aging and Disease

   This article has 6 authors:

   1. Achal Mahajan
   2. Francesca Ratti
   3. Ban Wang
   4. Hana El-Samad
   5. James H Kaufman
   6. Vishrawas Gopalakrishnan

   This article has been curated by 1 group:

   • Curated by eLife

     eLife Assessment

     This valuable study analyzes aging-related chromatin changes through the lens of intra-chromosomal gene correlation length, which is a novel computational metric that captures spatial correlations in gene expression along the chromosome. The authors propose that this metric reflects chromatin structure and can serve as a proxy for its changes during aging. While currently the strength of evidence is somewhat incomplete, if revised with further supporting data, this work will provide a systems-level understanding of aging and genome regulation, which is predicted to have a substantive impact on the field.

   Reviewed by eLife

9. Regulation of Transcriptional Bursting and Spatial Patterning in Early Drosophila Embryo Development

   This article has 4 authors:

   1. César Nieto
   2. Zahra Vahdat
   3. Bomyi Lim
   4. Abhyudai Singh

   This article has been curated by 1 group:

   • Curated by eLife

     eLife Assessment

     This study presents a valuable quantitative framework for analyzing transcription dynamics data for enhancers and genes expressed in the early Drosophila embryo. By analyzing existing data across both synthetic reporters and an endogenous gene (eve), this work provides evidence that spatial gene expression patterns within the embryo are largely determined by "activity time" - the time during which a gene is bursting. The methods and evidence are solid and should be of broad interest to researchers in developmental biology and quantitative gene regulation, but the study would be significantly enhanced by clarifying the novelty of the findings relative to prior work and presenting a rigorous benchmarking of their algorithm against previously used algorithms.

   Reviewed by eLife

10. A Python Toolbox for Representational Similarity Analysis

    This article has 11 authors:

    1. Jasper JF van den Bosch
    2. Tal Golan
    3. Benjamin Peters
    4. JohnMark Taylor
    5. Mahdiyar Shahbazi
    6. Baihan Lin
    7. Ian Charest
    8. Jörn Diedrichsen
    9. Nikolaus Kriegeskorte
    10. Marieke Mur
    11. Heiko H Schütt

    This article has been curated by 1 group:

    • Curated by eLife

      eLife Assessment

      This study presents a new toolbox for Representational Similarity Analysis, representing a valuable contribution to the neuroscience community. The authors offer a well-integrated platform that brings together a range of state-of-the-art methodological advances within a convincing framework, with strong potential to enable more rigorous and insightful analyses of neural data across multiple subfields.

    Reviewed by eLife