Genomics

The genome of the mustard hill coral, Porites astreoides

1. Kevin H. Wong
2. Hollie M. Putnam

Reviewed by GigaByte

Uncovering perturbations in human hematopoiesis associated with healthy aging and myeloid malignancies at single-cell resolution

1. Marina Ainciburu
2. Teresa Ezponda
3. Nerea Berastegui
4. Ana Alfonso-Pierola
5. Amaia Vilas-Zornoza
6. Patxi San Martin-Uriz
7. Diego Alignani
8. Jose Lamo-Espinosa
9. Mikel San-Julian
10. Tamara Jiménez-Solas
11. Felix Lopez
12. Sandra Muntion
13. Fermin Sanchez-Guijo
14. Antonieta Molero
15. Julia Montoro
16. Guillermo Serrano
17. Aintzane Diaz-Mazkiaran
18. Miren Lasaga
19. David Gomez-Cabrero
20. Maria Diez-Campelo
21. David Valcarcel
22. Mikel Hernaez
23. Juan P Romero
24. Felipe Prosper

• Curated by eLife

  Evaluation Summary:

  The present manuscript provides a valuable single-cell transcriptomic resource to understand normal hematopoiesis in humans and the age-dependent cellular and molecular alterations. It addresses very important questions in hematopoietic stem cell biology, such as the molecular changes underlying their aging and their perturbation in the context of myelodysplastic syndrome, and will be of interest to readers in the field of hematopoiesis and associated diseases, aging, and single-cell RNA sequencing.

  (This preprint has been reviewed by eLife. We include the public reviews from the reviewers here; the authors also receive private feedback with suggested changes to the manuscript. Reviewer #2 agreed to share their name with the authors.)

Reviewed by eLife

Activity-based CRISPR scanning uncovers allostery in DNA methylation maintenance machinery

1. Kevin Chun-Ho Ngan
2. Samuel M Hoenig
3. Hui Si Kwok
4. Nicholas Z Lue
5. Pallavi M Gosavi
6. David A Tanner
7. Emma M Garcia
8. Ceejay Lee
9. Brian B Liau

• Curated by eLife

  Evaluation Summary:

  This highly interesting manuscript will be relevant to colleagues studying cancer and those developing cancer therapies. The work describes the use of a large-scale CRISPR screen to identify mechanisms underlying resistance to the hypomethylating anti-cancer agent decitabine, which acts by inhibiting the DNA methyltransferase DNMT1. A specific focus is given to allosteric mechanisms of resistance that emerge, including those that appear to act as gain-of-function mutations in both DNMT1 and its interacting partner UHRF1. These findings showcase the power of large-scale genomic editing screens for the discovery of novel drug resistance mechanisms, which may guide the development of next-generation cancer therapies.

  (This preprint has been reviewed by eLife. We include the public reviews from the reviewers here; the authors also receive private feedback with suggested changes to the manuscript. The reviewers remained anonymous to the authors.)

Reviewed by eLife

A method for low-coverage single-gamete sequence analysis demonstrates adherence to Mendel’s first law across a large sample of human sperm

1. Sara A Carioscia
2. Kathryn J Weaver
3. Andrew N Bortvin
4. Hao Pan
5. Daniel Ariad
6. Avery Davis Bell
7. Rajiv C McCoy

• Curated by eLife

  Evaluation Summary:

  The authors first develop a new flexible and robust method to detect deviations from Mendelian inheritance in genomic data from gametes. The authors then apply this method to study deviations from Mendelian inheritance in human sperm data, but find no evidence for it. Even though this is a negative result, and overall the results are expected based on previous studies. the reviewers agreed that the research is rigorous and valuable.

  (This preprint has been reviewed by eLife. We include the public reviews from the reviewers here; the authors also receive private feedback with suggested changes to the manuscript. The reviewers remained anonymous to the authors.)

Reviewed by eLife

Long-read HiFi sequencing correctly assembles repetitive heavy fibroin silk genes in new moth and caddisfly genomes

1. Akito Y. Kawahara
2. Caroline G. Storer
3. Amanda Markee
4. Jacqueline Heckenhauer
5. Ashlyn Powell
6. David Plotkin
7. Scott Hotaling
8. Timothy P. Cleland
9. Rebecca B. Dikow
10. Torsten Dikow
11. Ryoichi B. Kuranishi
12. Rebeccah Messcher
13. Steffen U. Pauls
14. Russell J. Stewart
15. Koji Tojo
16. Paul B. Frandsen

Reviewed by GigaByte

CRISPR interference identifies vulnerable cellular pathways with bactericidal phenotypes in Mycobacterium tuberculosis

1. Matthew B. McNeil
2. Laura M. Keighley
3. Josephine R. Cook
4. Chen‐Yi Cheung
5. Gregory M. Cook

• Curated by eLife

  Evaluation Summary:

  High-throughput approaches that accurately assess drug target vulberbility in Mycobacterium tuberculosis, the causative agent of tuberculosis, are urgently needed to develop new treatment options for this dreaded disease. This paper applies a CRISPRi based approach to investigate gene essentiality and vulnerability on a diverse set of 96 genes. While the key observations of the study support previous findings, the approach reported here is useful for identification and characterization of novel drug targets. The study will be of interest to microbiologists and those interested in diverse aspects of bacterial metabolism.

  (This preprint has been reviewed by eLife. We include the public reviews from the reviewers here; the authors also receive private feedback with suggested changes to the manuscript. Reviewer #1 agreed to share their name with the authors.)

Reviewed by eLife

Tethering distinct molecular profiles of single cells by their lineage histories to investigate sources of cell state heterogeneity

1. Anna Minkina
2. Junyue Cao
3. Jay Shendure

• Curated by eLife

  Evaluation Summary:

  The authors use single-cell RNA-sequencing, single-cell ATAC-sequencing, a CRISPR-based lineage tracing system, and a novel computational pipeline to characterize heritable expression changes. Aspects of this work were found to be both impactful and technically sound, but there is a concern with the scalability/generalizability of the approach, the use of the single cell ATAC-sequencing data, and some technical aspects of the computational pipeline. This work will appeal to groups working on lineage tracing and gene regulation.

  (This preprint has been reviewed by eLife. We include the public reviews from the reviewers here; the authors also receive private feedback with suggested changes to the manuscript. Reviewer #2 agreed to share their name with the authors.)

Reviewed by eLife

Condensin DC loads and spreads from recruitment sites to create loop-anchored TADs in C. elegans

1. Jun Kim
2. David S Jimenez
3. Bhavana Ragipani
4. Bo Zhang
5. Lena A Street
6. Maxwell Kramer
7. Sarah E Albritton
8. Lara H Winterkorn
9. Ana K Morao
10. Sevinc Ercan

• Curated by eLife

  Evaluation Summary:

  This paper is potentially of broad interest to researchers in the chromosome biology field. With specific loading sequences identified, the condensin DC complex studied here provides an elegant system to investigate the in vivo activities of SMC complexes. Combining Hi-C, ChIP-seq and RNA-seq, the authors have a comprehensive suite of assays to probe their questions. However, not all of their major conclusions are currently supported by the data.

  (This preprint has been reviewed by eLife. We include the public reviews from the reviewers here; the authors also receive private feedback with suggested changes to the manuscript. The reviewers remained anonymous to the authors.)

Reviewed by eLife

Mapping the single-cell landscape of acral melanoma and analysis of the molecular regulatory network of the tumor microenvironments

1. Zan He
2. Zijuan Xin
3. Qiong Yang
4. Chen Wang
5. Meng Li
6. Wei Rao
7. Zhimin Du
8. Jia Bai
9. Zixuan Guo
10. Xiuyan Ruan
11. Zhaojun Zhang
12. Xiangdong Fang
13. Hua Zhao

• Curated by eLife

  Evaluation Summary:

  He and collaborators analyse eight samples from six patients with acral melanoma through single-cell RNA sequencing. They describe the tumour microenvironment in these tumours, including descriptions of interactions among distinct cell types and potential biomarkers. The study is thoroughly done. In its final form, this study will help to inform our knowledge of the immune infiltration on the poorly studied acral melanoma subtype, the most common type of the disease in several countries in Africa, Asia and Latin America.

  (This preprint has been reviewed by eLife. We include the public reviews from the reviewers here; the authors also receive private feedback with suggested changes to the manuscript. Reviewer #1 agreed to share their name with the authors.)

Reviewed by eLife

Reinvestigation of Classic T Cell Subsets and Identification of Novel Cell Subpopulations by Single-Cell RNA Sequencing

1. Xuefei Wang
2. Xiangru Shen
3. Shan Chen
4. Hongyi Liu
5. Ni Hong
6. Hanbing Zhong
7. Xi Chen
8. Wenfei Jin

• Curated by eLife

  Evaluation Summary:

  This manuscript is of broad interest to readers interested in heterogeneity in immune cell populations with single-cell RNA sequencing, and for students of human T cell biology. It uses and reanalyses published single-cell RNA sequencing data dataset for this purpose. However, it does not adequately address major technical concerns, and therefore the interpretations are not robustly supported.

  (This preprint has been reviewed by eLife. We include the public reviews from the reviewers here; the authors also receive private feedback with suggested changes to the manuscript. The reviewers remained anonymous to the authors.)

Reviewed by eLife