Genomics

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. Lucía Bilbao
3. Vanina A Campo
4. Joaquín Garat
5. José Sotelo-Silveira
6. Gabriel Rinaldi
7. Virginia M Howick
8. María Ana 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

Evolutionary remodeling of non-canonical ORF translation in mammals

1. Yue Chang
2. Tianyu Lei
3. Feng Zhou
4. Jiawen Jiang
5. Yu Huang
6. Ziyang Zhu
7. Hong Zhang

• Curated by eLife

  eLife Assessment

  This study presents a large, systematically curated catalog of non-canonical open reading frames (ncORFs) in human and mouse by reanalyzing nearly 400 Ribo-seq datasets using a standardized pipeline; the resulting atlas consolidates ncORF annotations across tissues and provides a valuable reference for understanding non-canonical translation and ORF emergence. The main conclusions are supported by consistent data processing and multiple computational measures of translation and conservation. While the pipeline is transparent and robust, several downstream analyses are descriptive, and some evolutionary interpretations remain correlative; dataset heterogeneity, uneven tissue representation, and limited experimental validation also constrain the strength of a subset of the findings. Overall, the evidence is solid, and the resource will be broadly used by the community.

Reviewed by Arcadia Science, eLife

Flexible and high-throughput simultaneous profiling of gene expression and chromatin accessibility in single cells

1. Volker Soltys
2. Moritz Peters
3. Dingwen Su
4. Marek Kučka
5. Yingguang Frank Chan

• Curated by eLife

  eLife Assessment

  This study presents a useful methodological advance that better enables the simultaneous measurement of gene expression and chromatin accessibility in individual cells. The evidence supporting the improved detection of gene expression is solid, though the reduced performance in detecting chromatin accessibility represents a limitation. This method will be of interest to those studying transcription and gene regulation.

Reviewed by eLife

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

Viral metagenomics of synanthropic urban bats: a surveillance strategy for uncovering potentially zoonotic viruses

1. Juliana Amorim Conselheiro
2. Filipe Romero Rebello Moreira
3. Gisely Toledo Barone
4. Adriana Araujo Reis-Menezes
5. Adriana Rückert da Rosa
6. Débora Cardoso de Oliveira
7. Bárbara Aparecida Chaves
8. Vanderson de Souza Sampaio
9. Felipe Rocha
10. Marco Antonio Natal Vigilato
11. Rodrigo Guerino Stabeli
12. Rodrigo Fabiano do Carmo Said
13. Gabriel Luz Wallau
14. Paulo Eduardo Brandão
15. Anderson Fernandes de Brito

Reviewed by Rapid Reviews Infectious Diseases

Population structure and antimicrobial resistance of Corynebacterium diphtheriae in Victoria, Australia

1. Lamali Sadeesh Kumar
2. Kylie Hui
3. Janet Strachan
4. Norelle L. Sherry
5. Benjamin P. Howden
6. Sarah L. Baines

Reviewed by Rapid Reviews Infectious Diseases