Genomics

Maximizing CRISPRi efficacy and accessibility with dual-sgRNA libraries and optimal effectors

1. Joseph M Replogle
2. Jessica L Bonnar
3. Angela N Pogson
4. Christina R Liem
5. Nolan K Maier
6. Yufang Ding
7. Baylee J Russell
8. Xingren Wang
9. Kun Leng
10. Alina Guna
11. Thomas M Norman
12. Ryan A Pak
13. Daniel M Ramos
14. Michael E Ward
15. Luke A Gilbert
16. Martin Kampmann
17. Jonathan S Weissman
18. Marco Jost

• Curated by eLife

  eLife Assessment:

  Replogle et al. present their design of a compact and functionally validated dual sgRNA libary and dCas9-effector protein that will enable new forms of CRISPRi-based screening in mammalian cells. Quantitative comparisons to previously published standards demonstrate strengths and weaknesses, which, along with the protocols and design strategies outlined, should enable end users to rapidly adopt their approach.

  (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

Integrative analysis of metabolite GWAS illuminates the molecular basis of pleiotropy and genetic correlation

1. Courtney J Smith
2. Nasa Sinnott-Armstrong
3. Anna Cichońska
4. Heli Julkunen
5. Eric B Fauman
6. Peter Würtz
7. Jonathan K Pritchard

• Curated by eLife

  Evaluation Summary:

  The paper by Smith and colleagues provides a framework for understanding a seemingly paradoxical observation in human genetics: two phenotypes may be closely correlated to each other, and the patterns of genetic variation that influence both phenotypes may be widely shared at the genome-wide level, but there are often specific genetic variants that show discordant patterns. Though the observations in this paper are derived from analysis of metabolic phenotypes, this may have broader relevance to interpreting the results from disease-related genetic association studies, and shed light on the processes that connect different disease phenotypes.

  (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 and Reviewer #2 agreed to share their names with the authors.)

Reviewed by eLife

Sex-based de novo transcriptome assemblies of the parasitoid wasp Encarsia suzannae, a host of the manipulative heritable symbiont Cardinium hertigii

1. Dylan L. Schultz
2. Evelyne Selberherr
3. Corinne M. Stouthamer
4. Matthew R. Doremus
5. Suzanne E. Kelly
6. Martha S. Hunter
7. Stephan Schmitz-Esser

Reviewed by GigaByte

The genome of a giant (trevally): Caranx ignobilis

1. Brandon D. Pickett
2. Jessica R. Glass
3. Timothy P. Johnson
4. Perry G. Ridge
5. John S. K. Kauwe

Reviewed by GigaByte

Predicting mechanisms of action at genetic loci associated with discordant effects on type 2 diabetes and abdominal fat accumulation

1. Yonathan Tamrat Aberra
2. Lijiang Ma
3. Johan LM Björkegren
4. Mete Civelek

• Curated by eLife

  Evaluation Summary:

  This study reports candidate causal genes in genome-wide association studies that exhibit a discordant pattern of association, namely a higher waist-hip ratio simultaneously with a lowered risk of type 2 diabetes. Identification of such genes could provide insights into why some individuals with obesity are not developing type 2 diabetes, knowledge that ultimately could shed light on the complex interplay between fat distribution and type 2 diabetes. The work is of relevance to the fields of genetics of diabetes and obesity.

  (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 and Reviewer #2 agreed to share their name with the authors.)

Reviewed by eLife

First De novo whole genome sequencing and assembly of mutant Dendrobium hybrid cultivar ‘Emma White’

1. Rubina Sherpa
2. Ramgopal Devadas
3. Penna Suprasanna
4. Sadashiv Narayan Bolbhat
5. Tukaram Dayaram Nikam

Reviewed by GigaByte

Characterization of full-length CNBP expanded alleles in myotonic dystrophy type 2 patients by Cas9-mediated enrichment and nanopore sequencing

1. Massimiliano Alfano
2. Luca De Antoni
3. Federica Centofanti
4. Virginia Veronica Visconti
5. Simone Maestri
6. Chiara Degli Esposti
7. Roberto Massa
8. Maria Rosaria D'Apice
9. Giuseppe Novelli
10. Massimo Delledonne
11. Annalisa Botta
12. Marzia Rossato

• Curated by eLife

  Evaluation Summary:

  To precisely diagnose DM2 caused by CCTG repetition in CNBP, the authors established a Cas9-mediated target enrichment system followed by Nanopore sequencing and analysis. The authors are fully aware of the limitations of the current diagnostic tests of DM2 and efficiently presented what novel findings have been revealed by the Cas9 nanopore sequencing. The findings of the current study suggest that Cas9 nanopore sequencing can be very useful for accurate genetic diagnosis of DM2 and understanding the genotype-phenotype correlation of this disease.

  (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 and Reviewer #2 agreed to share their name with the authors.)

Reviewed by eLife

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