Systems Biology

Metabolic Trans-Omic Analysis Reveals Key Regulatory Disruption of Energy Metabolism in Alzheimer’s Disease

1. Tomoharu Katayama
2. Hikaru Sugimoto
3. Keigo Morita
4. Hirohisa Watanabe
5. Shinya Kuroda

• Curated by eLife

  eLife Assessment

  This study presents a useful application of trans-omic network analyses to existing human brain datasets, generating systems-level insights into metabolic dysregulation in Alzheimer's disease. Overall, the authors' analytical choices are solid, with appropriate use of existing data and methods, and with many of their results confirming previous findings. However, some of the authors' key claims, related to previously unknown details of regulatory relationships, are only partially supported due to limitations in dataset cell-type resolution and network robustness, as well as a lack of functional validation. This work will be of interest to cellular or systems neurobiologists studying Alzheimer's disease and could serve as a helpful starting point for future work.

  [Editors' note: this paper was reviewed by Review Commons.]

Reviewed by eLife, Review Commons

Benchmarking biochemical networks generated by large language models

1. Jeevan Tewari
2. Benjamin W Dahl
3. B Adam Bates
4. Jason A Papin
5. Jeffrey J Saucerman

• Curated by eLife

  eLife Assessment

  The authors propose a pipeline using large language models (LLMs) to benchmark experimentally well validated computational models of signaling networks. The findings are important, with available methods that guide testing future models and find new molecular interactions. Furthermore, the work shows how general-purpose LLMs can generate up to 91% of reactions of a bacterial metabolic network. The support is convincing and offers a number of performance metrics.

Reviewed by eLife

Signatures of digital Polycomb regulation in functional iPSC heterogeneity between individuals

1. Ander Movilla Miangolarra
2. Julia Kurlovich
3. Fereshteh Torabi
4. Oleksandr Dovgusha
5. Yang Cao
6. Lihan Lin
7. Ufuk Günesdogan
8. Stefan Schoenfelder
9. Martin Howard

Reviewed by Review Commons

The zoo of the gene networks capable of pattern formation by extracellular signaling

1. Kevin Martinez-Anhom
2. Isaac Salazar-Ciudad

• Curated by eLife

  eLife Assessment

  The study presents a valuable conceptual framework by classifying pattern-forming gene subnetworks into three established categories. However, the supporting evidence remains incomplete, as the mathematical generalizations rely on simplified assumptions that may not hold in more complex or realistic scenarios.

Reviewed by eLife

Diurnal rhythmicity in metabolism and salivary effector expression shapes aphid performance on host plants

1. Jinlong Han
2. Daniel Kunk
3. Meihua Cui
4. Yoshiahu Goldstein
5. Vered Tzin
6. Vamsi J Nalam

• Curated by eLife

  eLife Assessment

  In this study, the authors found that a species of aphid that is a known agricultural pest salivated longer and produced more honeydew when feeding at night. The authors identified aphid genes with diurnal expression patterns, including potential salivation-related genes. Silencing these genes reduced aphid performance only on plants and not on artificial diet, suggesting a specific role in plant feeding. This study is valuable for understanding plant-insect interactions in agriculture and presents solid evidence of diurnal rhythmicity in aphid activity and performance, although further research is needed to elucidate the function of the identified genes.

Reviewed by eLife

Towards pharmacokinetic profile predictions for monoclonal antibodies using sequence based machine learning derived parameters and compartmental modeling

1. Felix Jost
2. Henrik Cordes

Reviewed by PREreview

Five-layer systems analysis of Leishmania stage differentiation reveals an essential role for protein degradation in parasite development

1. Pascale Pescher
2. Thibaut Douché
3. Quentin Giai-Gianetto
4. Karen Druart
5. Julie Kovarova
6. Blaise Li
7. Thomas Cokelaer
8. K Shanmugha Rajan
9. Laura Piel
10. Céline Besse
11. Anne Boland
12. Jean-François Deleuze
13. Mariette Matondo
14. Michael P Barrett
15. Shulamit Michaeli
16. Gerald F Späth

• Curated by eLife

  eLife Assessment

  This important study provides a comprehensive multi-omics characterization of Leishmania donovani stage differentiation, offering insights into the molecular basis of parasite adaptation across host environments. The authors present convincing evidence that stage transitions are not driven by genomic variation but instead rely on coordinated post-transcriptional regulation, including mRNA turnover, translation, and protein degradation. Although experimental validation of these findings and conclusions remains to be completed, the integration of diverse, high-quality datasets establishes a robust resource that will be of broad utility to researchers investigating Leishmania biology and life-cycle progression.

  [Editors' note: this paper was reviewed by Review Commons.]

Reviewed by eLife, Review Commons

Evolutionary rewiring of host metabolism and interferon signalling by SARS-CoV-2 variants

1. Riaz-Ali Somji
2. Jonathan C Brown
3. Shahid Rowles-Khalid
4. Tukur Abdullahi
5. Dongsheng Luo
6. Natalie Barthel
7. Michael Mülleder
8. Markus Ralser
9. Wendy S Barclay
10. Charalampos Rallis
11. Efstathios S Giotis

Reviewed by Review Commons

Computational Model of Flower Pattern Evolution Predicts Spontaneous Emergence of Boundary Cell Types Across Petal Epidermis

1. Steven Oud
2. Maciej M. Żurowski
3. Pjotr L. van der Jagt
4. May T. S. Yeo
5. Joseph F. Walker
6. Edwige Moyroud
7. Renske M. A. Vroomans

Reviewed by Review Commons

Thymic selection of the T cell receptor repertoire is biased toward autoimmunity in females

1. Hélène Vantomme
2. Valentin Quiniou
3. Leslie Adda
4. Charline Jouannet
5. Vanessa Mhanna
6. Céline Albalaa
7. Pierre Barennes
8. Nicolas Coatnoan
9. Vimala Diderot
10. Johanna Dubois
11. Gwladys Fourcade
12. Kenz Le Gouge
13. Otriv Frédéric Nguekap Tchoumba
14. Martin Pezous
15. Paul Stys
16. Adrien Six
17. Encarnita Mariotti-Ferrandiz
18. David Klatzmann

• Curated by eLife

  eLife Assessment

  This study provides valuable insights into addressing the question of whether the prevalence of autoimmune disease could be driven by sex differences in the T cell receptor (TCR) repertoire, correlating with higher rates of autoimmune disease in females. The authors compared male and female TCR repertoires using bulk RNA sequencing, from sorted thymocyte subpopulations in pediatric and adult human thymuses; however, the analyses provided do not provide sufficient discrimination, as paired TCR chains are not examined, and incompletely support the central claims regarding sex differences in the TCR repertoire and potential autoimmune bias.

Reviewed by eLife