Genomics

Structure-guided isoform identification for the human transcriptome

1. Markus J Sommer
2. Sooyoung Cha
3. Ales Varabyou
4. Natalia Rincon
5. Sukhwan Park
6. Ilia Minkin
7. Mihaela Pertea
8. Martin Steinegger
9. Steven L Salzberg

• Curated by eLife

  eLife assessment

  This study applies AlphaFold to the CHESS selection of transcripts with the goal of generating predicted 3D protein structures and a quality measure of folding, the pLDDT score. From these data, the authors build a database for result exploration, documented by several examples, including proteins, where the authors propose the pLDDT score as a measure of presumed superior biological functionality over other isoforms. These results will be highly relevant for anyone working with proteins that occur in different isoforms.

Reviewed by eLife

Promoter sequence and architecture determine expression variability and confer robustness to genetic variants

1. Hjörleifur Einarsson
2. Marco Salvatore
3. Christian Vaagensø
4. Nicolas Alcaraz
5. Jette Bornholdt
6. Sarah Rennie
7. Robin Andersson

• Curated by eLife

  eLife assessment

  This paper by Einarsson and colleagues presents a comprehensive analysis on how human genetic variability impacts both gene expression and promoter. Using a new resource of CAGE data in lymphoblastoid cell lines from 108 individuals, they uncover a series of features that distinguish promoters with highly variable expression across individuals from those exhibiting low variability. The authors propose various explanations for the observed results. A few additional analyses and a more pragmatic interpretation of their data may help consolidate or refine the models proposed.

Reviewed by eLife

Brown adipocytes local response to thyroid hormone is required for adaptive thermogenesis in adult male mice

1. Yanis Zekri
2. Romain Guyot
3. Inés Garteizgogeascoa Suñer
4. Laurence Canaple
5. Amandine Gautier Stein
6. Justine Vily Petit
7. Denise Aubert
8. Sabine Richard
9. Frédéric Flamant
10. Karine Gauthier

• Curated by eLife

  eLife assessment

  The manuscript by Yanis Zekri et al identifies the direct T3 target genes that are important in thyroid hormone signaling in brown adipose tissue (BAT). The findings reported in this manuscript are significant and fundamental to our understanding of thyroid hormone action in response to environmental changes. The strength of the evidence presented with the novel methodological approaches used makes the manuscript exceptional in the area of BAT biology and T3 regulation of adaptive thermogenesis.

Reviewed by eLife

Transcriptional profiling of Hutchinson-Gilford Progeria syndrome fibroblasts reveals deficits in mesenchymal stem cell commitment to differentiation related to early events in endochondral ossification

1. Rebeca San Martin
2. Priyojit Das
3. Jacob T Sanders
4. Ashtyn M Hill
5. Rachel Patton McCord

• Curated by eLife

  eLife assessment

  This manuscript is of interest to researchers investigating genetic mechanisms of aging and transcriptional regulation of developmental processes in mesenchyme-derived tissues. In this study, fibroblast cell lines from patients with and without Hutchinson-Gilford Progeria were compared to pinpoint the molecular mechanisms leading to the phenotypes of persons with this condition. The identification of five major dysregulated functional hubs in fibroblast cell lines derived from Hutchinson-Gilford Progeria Syndrome (HGPS) patients provides a unique opportunity for others working on this disorder to utilize animal models to validate the authors' hypotheses.

Reviewed by eLife

Mouse B2 SINE elements function as IFN-inducible enhancers

1. Isabella Horton
2. Conor J Kelly
3. Adam Dziulko
4. David M Simpson
5. Edward B Chuong

• Curated by eLife

  eLife assessment

  This paper will be of interest to scientists studying species-specific immune responses and those studying how transposable elements rewire transcriptional regulatory networks. The work describes a new class of TEs that may act as enhancers of immune genes in mice. A combination of computational and experimental data supports most but not all conclusions in the paper.

Reviewed by eLife

A phased, chromosome-scale genome of ‘Honeycrisp’ apple (Malus domestica)

1. Awais Khan
2. Sarah B. Carey
3. Alicia Serrano
4. Huiting Zhang
5. Heidi Hargarten
6. Haley Hale
7. Alex Harkess
8. Loren Honaas

Reviewed by GigaByte

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