Genomics

Optics-free reconstruction of shapes, images and volumes with DNA barcode proximity graphs

1. Hanna Liao
2. Sanjay Kottapalli
3. Yuqi Huang
4. Matthew Chaw
5. Jase Gehring
6. Olivia Waltner
7. Melissa Phung-Rojas
8. Riza M Daza
9. Frederick A Matsen
10. Cole Trapnell
11. Jay Shendure
12. Sanjay Srivatsan

• Curated by eLife

  eLife Assessment

  This important technical study introduces SCOPE, an optics-free spatial reconstruction method based on bidirectional sender and receiver oligonucleotides on barcoded hydrogel beads. By sequencing proximity-encoded chimeric molecules, the authors computationally reconstruct 2D and 3D spatial information at an impressive scale. The technical demonstrations in synthetic bead systems are convincing and establish proof-of-principle that large spatial domains can be reconstructed without microscopy. The methodological advance is clear and the scale is impressive. Direct validation in biological samples would help clarify what additional limitations on applicability may exist. This work will be of interest to those working on spatial mapping.

Reviewed by eLife

Sex Chromosome Turnover and Structural Interspecific Genome Divergence Shapes Meiotic Outcomes in Hybridizing Cobitis

1. S. A. Schlebusch
2. V. Trifonov
3. Z. Halenková
4. M. Klianitskaya
5. D. Dedukh
6. A. Ruiz Herrera
7. L. Álvarez González
8. G. Pujol Infantes
9. E. Hřibová
10. L. Andjel
11. O. Bartoš
12. P. Pajer
13. T. Tichopád
14. D. Kulik
15. J. Kotusz
16. M. Kaštánková Doležálková
17. A. Bohne
18. A. Marta
19. P. Horna
20. R. Reifová
21. Y. Guiguen
22. J. Pačes
23. K. Janko

Reviewed by GigaScience

Stranded short nascent strand sequencing reveals the topology of DNA replication origins in Trypanosoma brucei

1. Slavica Stanojcic
2. Bridlin Barckmann
3. Pieter Monsieurs
4. Lucien Crobu
5. Simon George
6. Yvon Sterkers

• Curated by eLife

  eLife Assessment

  The authors adapt sequencing of nascent DNA (DNA linked to an RNA primer, "SNS-Seq") to map DNA replication origins in Trypanosoma brucei. The main impact of this work is reporting a new set of putative origins, which do not overlap with previously reported origins, but which appear to overlap with previously mapped DNA-RNA hybrid (R-loops). Thus, these valuable findings open up new avenues for further investigation into the mechanistic basis for firing of replication forks in this organism. However, the supporting evidence remains incomplete and would benefit from orthogonal validation. This work will be of interest to those studying DNA replication and epigenetic regulation of fork origins.

Reviewed by eLife

The CLAMP GA-binding transcription factor regulates heat stress-induced transcriptional repression

1. Joseph Aguilera
2. Jingyue Duan
3. Kaitlyn Cortez
4. Rachel S Lee
5. Angelica Aragon
6. Mukulika Ray
7. Erica Larschan

• Curated by eLife

  eLife Assessment

  This important study presents evidence that the Chromatin-linked adaptor for MSL complex proteins (CLAMP) GA-binding transcription factor (TF) regulates ~75% of HS-induced repression in Drosophila and suggests that CLAMP is the first known transcription factor to induce heat-stress-mediated repression of gene expression. While mechanistic details remain to be sorted out, this manuscript provides convincing evidence that novel pathways involving the CLAMP transcription factor repress gene expression during heat shock stress.

Reviewed by eLife

Single-cell co-mapping reveals relationship between chromatin state and gene expression in early zebrafish development

1. Vivek Bhardwaj
2. Alberto Griffa
3. Helena Viñas Gaza
4. Peter Zeller
5. Alexander van Oudenaarden

• Curated by eLife

  eLife Assessment

  In this valuable study, the authors examine transcription and chromatin dynamics during early zebrafish development by simultaneously profiling histone modifications and full-length transcriptomes in thousands of single cells, providing solid analysis that chromatin and transcriptional states are initially weakly correlated in early embryonic cells and become progressively more aligned as differentiation proceeds. The work also supports a model in which promoter-anchored cis-spreading of H3K27me3 contributes to stable gene silencing during development. Future functional perturbations and orthogonal validations will be needed to determine the causal contribution of Polycomb spreading to fate commitment. Overall, the dataset and accompanying analyses provide a robust resource and a quantitative framework for studying chromatin-transcription relationships during vertebrate embryogenesis.

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

Reviewed by eLife, Review Commons

Deep mutational scanning reveals pharmacologically relevant insights into TYK2 signaling and disease

1. Conor J Howard
2. Nathan S Abell
3. Robert R Warneford-Thomson
4. Eden Mahdavi
5. Alan L Su
6. Carmen Resnick
7. Nabil Mohammed
8. Erin M Thompson
9. Emily R Holzinger
10. Katrina Catalano
11. Abhay Hukku
12. Gabriel A Mintier
13. Morgan MacKenzie
14. Bryan L Jiang
15. Dora Barbosa Rabago
16. Angela Chan
17. Carolindah Ntimi
18. Kaitlyn N Weiler
19. Stephen C Wilson
20. Joseph C Maranville
21. Payal R Sheth
22. Robert M Plenge
23. Sriram Kosuri
24. Diane E Dickel

• Curated by eLife

  eLife Assessment

  This important paper presents a rigorous and comprehensive deep mutational analysis of the kinase TYK2, revealing how single amino acid substitutions influence protein abundance, signaling activity, and responses to pharmacological inhibitors. By combining high‑quality experimental design with dose‑response signaling assays and multiple inhibitor conditions, the authors generate a robust dataset that identifies variants across all domains of TYK2, including clusters at functionally critical sites and protein-protein interfaces. The study highlights mutations that drive drug resistance or potentiation and shows that reduced TYK2 abundance aligns with protective autoimmune‑associated variants, underscoring the therapeutic relevance of modulating TYK2 stability. Overall, the work provides compelling insights with clear implications for biochemistry, immunology, clinical genetics, and drug discovery.

Reviewed by eLife

Single-cell RNA-seq reveals trans-sialidase-like superfamily gene expression heterogeneity in Trypanosoma cruzi populations

1. Lucas Inchausti
2. Lucia Bilbao
3. Vanina A Campo
4. Joaquín Garat
5. José Sotelo-Silveira
6. Gabriel Rinaldi
7. Virginia M Howick
8. Maria A Duhagon
9. Javier G De Gaudenzi
10. Pablo Smircich

• Curated by eLife

  eLife Assessment

  This study provides important insights into how Trypanosoma cruzi populations diversify surface protein expression, showing through single-cell RNA sequencing that trans-sialidase-like genes are expressed heterogeneously across individual parasites, a pattern with clear implications for immune evasion. The evidence is convincing, supported by robust single-cell transcriptomic analyses, consistent quantitative measures of expression heterogeneity, and integration with genomic organization that together argue against purely stochastic expression.

Reviewed by eLife

Transcriptional perturbation of LINE-1 elements reveals their cis -regulatory potential

1. Yuvia A Pérez-Rico
2. Aurélie Bousard
3. Lenka Henao Misikova
4. Eskeatnaf Mulugeta
5. Sérgio F de Almeida
6. Alysson R Muotri
7. Edith Heard
8. Anne-Valerie Gendrel

Reviewed by Review Commons

Intestinal Receptor of SARS-CoV-2 in Inflamed IBD Tissue Seems Downregulated by HNF4A in Ileum and Upregulated by Interferon Regulating Factors in Colon

1. Bram Verstockt
2. Sare Verstockt
3. Saeed Abdu Rahiman
4. Bo-jun Ke
5. Kaline Arnauts
6. Isabelle Cleynen
7. João Sabino
8. Marc Ferrante
9. Gianluca Matteoli
10. Séverine Vermeire

Reviewed by Rapid Reviews Infectious Diseases, ScreenIT

Genomic and epidemiologic characteristics of SARS-CoV-2 persistent infections in California, January 2021 - July 2023

1. John M. Bell
2. Jesse Elder
3. Rahil Ryder
4. Emily A. Smith
5. Michelle Scribner
6. Sabrina Gilliam
7. Deva Borthwick
8. Megan Crumpler
9. Jacek Skarbinski
10. Christina Morales
11. Debra A. Wadford

Reviewed by Rapid Reviews Infectious Diseases