Genomics

Discovering non-additive heritability using additive GWAS summary statistics

1. Samuel Pattillo Smith
2. Gregory Darnell
3. Dana Udwin
4. Julian Stamp
5. Arbel Harpak
6. Sohini Ramachandran
7. Lorin Crawford

• Curated by eLife

  eLife assessment

  This study provides a valuable investigation into whether phenotypic variance due to interactions between genetic variants can be measured using genome-wide association summary statistics. The authors present a method, i-LDSC, that uses statistics on the correlations between genotypes at different loci (linkage disequilibrium) to estimate the phenotypic variance explained by both additive genetic effects and pairwise interactions. While the authors present extensive simulations on the performance of their method and empirical results indicating the presence of epistasis (as they define epistasis) it is unclear how their method and results relate to the traditional definitions of additive and non-additive genetic effects, which are different from the authors' definitions.

Reviewed by eLife

Spatial chromatin accessibility sequencing resolves high-order spatial interactions of epigenomic markers

1. Yeming Xie
2. Fengying Ruan
3. Yaning Li
4. Meng Luo
5. Chen Zhang
6. Zhichao Chen
7. Zhe Xie
8. Zhe Weng
9. Weitian Chen
10. Wenfang Chen
11. Yitong Fang
12. Yuxin Sun
13. Mei Guo
14. Juan Wang
15. Shouping Xu
16. Hongqi Wang
17. Chong Tang

• Curated by eLife

  eLife assessment

  This paper reports the development of SCA-seq, a new method derived from PORE-C for simultaneously measuring chromatin accessibility, genome 3D and CpG DNA methylation. Most of the conclusions are supported by convincing data. SCA-seq has the potential to become a useful tool to the scientific communities to interrogate genome structure-function relationships.

Reviewed by eLife

Cis-regulatory modes of Ultrabithorax inactivation in butterfly forewings

1. Amruta Tendolkar
2. Anyi Mazo-Vargas
3. Luca Livraghi
4. Joseph J Hanly
5. Kelsey C Van Horne
6. Lawrence E Gilbert
7. Arnaud Martin

• Curated by eLife

  eLife assessment

  This valuable paper examines the Bithorax complex in several butterfly species, in which the complex is contiguous and not split, as it is in the well-studied fruit fly Drosophila. Based on genetic screens and genetic manipulations of a boundary element involved in segment-specific regulation of Ubx, the authors provide convincing evidence for their conclusions, which could be strengthened by additional data and analyses in the future. The data presented are relevant for those interested in the evolution and function of Hox genes and of gene regulation in general.

Reviewed by eLife

A Pooled Cell Painting CRISPR Screening Platform Enables de novo Inference of Gene Function by Self-supervised Deep Learning

1. Srinivasan Sivanandan
2. Bobby Leitmann
3. Eric Lubeck
4. Mohammad Muneeb Sultan
5. Panagiotis Stanitsas
6. Navpreet Ranu
7. Alexis Ewer
8. Jordan E. Mancuso
9. Zachary F Phillips
10. Albert Kim
11. John W. Bisognano
12. John Cesarek
13. Fiorella Ruggiu
14. David Feldman
15. Daphne Koller
16. Eilon Sharon
17. Ajamete Kaykas
18. Max R. Salick
19. Ci Chu

Reviewed by Arcadia Science

Characterization of caffeine response regulatory variants in vascular endothelial cells

1. Carly Boye
2. Cynthia A Kalita
3. Anthony S Findley
4. Adnan Alazizi
5. Julong Wei
6. Xiaoquan Wen
7. Roger Pique-Regi
8. Francesca Luca

• Curated by eLife

  eLife assessment

  This important study combines disease-associated genetic variation with a massively parallel reporter assay and different cellular perturbations to identify context-specific genetic regulatory effects. The methods and analyses are solid and the proposed functional variants will be helpful for experimental and quantitative geneticists studying a wide range of complex traits.

Reviewed by eLife

Long-read single-cell sequencing reveals expressions of hypermutation clusters of isoforms in human liver cancer cells

1. Silvia Liu
2. Yan-Ping Yu
3. Bao-Guo Ren
4. Tuval Ben-Yehezkel
5. Caroline Obert
6. Mat Smith
7. Wenjia Wang
8. Alina Ostrowska
9. Alejandro Soto-Gutierrez
10. Jian-Hua Luo

• Curated by eLife

  eLife assessment

  The authors pair single-cell sequencing technology with the LoopSeq synthetic long-read method to examine samples of hepatocellular carcinoma and benign liver, with the goal of identifying mutations and fusion transcripts specific to cancer cells. The authors present a valuable resource and the overall support for the major claims is solid.

Reviewed by eLife

Regulation of chromatin architecture by transcription factor binding

1. Stephanie Portillo-Ledesma
2. Suckwoo Chung
3. Jill Hoffman
4. Tamar Schlick

• Curated by eLife

  eLife assessment

  In this important study, chromatin is simulated as a polymer at the scale of genes, and the 3D organization of chromatin is analyzed at nucleosome resolution. There is convincing evidence for the emergence of chromatin microdomains due to the action of transcription factors, based on the simulation incorporating well-known biophysical properties of DNA, of nucleosomes, of linker histones, and of the transcription factor pair Myc:Max, as well as considering how the 3D organization of chromatin results from bending and looping of DNA. The work greatly improves our understanding of how the joint action of transcription factors and chromatin features affects chromatin structure and accessibility, which is of interest to anyone studying gene regulation.

Reviewed by eLife

Nucleosome conformation dictates the histone code

1. Matthew R Marunde
2. Harrison A Fuchs
3. Jonathan M Burg
4. Irina K Popova
5. Anup Vaidya
6. Nathan W Hall
7. Ellen N Weinzapfel
8. Matthew J Meiners
9. Rachel Watson
10. Zachary B Gillespie
11. Hailey F Taylor
12. Laylo Mukhsinova
13. Ugochi C Onuoha
14. Sarah A Howard
15. Katherine Novitzky
16. Eileen T McAnarney
17. Krzysztof Krajewski
18. Martis W Cowles
19. Marcus A Cheek
20. Zu-Wen Sun
21. Bryan J Venters
22. Michael-C Keogh
23. Catherine A Musselman

• Curated by eLife

  eLife assessment

  The manuscript investigates how the tandem reader domains in BPTF co-recognize two types of modifications present on histone tails, H3K4me3 and H3 acetylation. The authors interpret their results in the context of the conformational restriction of histone tails due to interactions with nucleosomal DNA. The findings contribute new insights into how the nucleosomal context regulates the recognition of multiple histone modifications by tandem reader domains and should be of interest to the broader chromatin field.

Reviewed by eLife

The landscape of tolerated genetic variation in humans and primates

1. Hong Gao
2. Tobias Hamp
3. Jeffrey Ede
4. Joshua G. Schraiber
5. Jeremy McRae
6. Moriel Singer-Berk
7. Yanshen Yang
8. Anastasia S. D. Dietrich
9. Petko P. Fiziev
10. Lukas F. K. Kuderna
11. Laksshman Sundaram
12. Yibing Wu
13. Aashish Adhikari
14. Yair Field
15. Chen Chen
16. Serafim Batzoglou
17. Francois Aguet
18. Gabrielle Lemire
19. Rebecca Reimers
20. Daniel Balick
21. Mareike C. Janiak
22. Martin Kuhlwilm
23. Joseph D. Orkin
24. Shivakumara Manu
25. Alejandro Valenzuela
26. Juraj Bergman
27. Marjolaine Rousselle
28. Felipe Ennes Silva
29. Lidia Agueda
30. Julie Blanc
31. Marta Gut
32. Dorien de Vries
33. Ian Goodhead
34. R. Alan Harris
35. Muthuswamy Raveendran
36. Axel Jensen
37. Idriss S. Chuma
38. Julie E. Horvath
39. Christina Hvilsom
40. David Juan
41. Peter Frandsen
42. Fabiano R. de Melo
43. Fabrício Bertuol
44. Hazel Byrne
45. Iracilda Sampaio
46. Izeni Farias
47. João Valsecchi do Amaral
48. Mariluce Messias
49. Maria N. F. da Silva
50. Mihir Trivedi
51. Rogerio Rossi
52. Tomas Hrbek
53. Nicole Andriaholinirina
54. Clément J. Rabarivola
55. Alphonse Zaramody
56. Clifford J. Jolly
57. Jane Phillips-Conroy
58. Gregory Wilkerson
59. Christian Abee
60. Joe H. Simmons
61. Eduardo Fernandez-Duque
62. Sree Kanthaswamy
63. Fekadu Shiferaw
64. Dongdong Wu
65. Long Zhou
66. Yong Shao
67. Guojie Zhang
68. Julius D. Keyyu
69. Sascha Knauf
70. Minh D. Le
71. Esther Lizano
72. Stefan Merker
73. Arcadi Navarro
74. Thomas Bataillon
75. Tilo Nadler
76. Chiea Chuen Khor
77. Jessica Lee
78. Patrick Tan
79. Weng Khong Lim
80. Andrew C. Kitchener
81. Dietmar Zinner
82. Ivo Gut
83. Amanda Melin
84. Katerina Guschanski
85. Mikkel Heide Schierup
86. Robin M. D. Beck
87. Govindhaswamy Umapathy
88. Christian Roos
89. Jean P. Boubli
90. Monkol Lek
91. Shamil Sunyaev
92. Anne O’Donnell-Luria
93. Heidi L. Rehm
94. Jinbo Xu
95. Jeffrey Rogers
96. Tomas Marques-Bonet
97. Kyle Kai-How Farh

Reviewed by Arcadia Science

Plasma growth hormone pulses induce male-biased pulsatile chromatin opening and epigenetic regulation in adult mouse liver

1. Andy Rampersaud
2. Jeannette Connerney
3. David J Waxman

• Curated by eLife

  eLife assessment

  This important study offers new and convincing support for the idea that about a third of mouse liver DNAse hypersensitivity sites (DHS) showing male-biased chromatin opening are sex-biased because of the male-specific cyclic action of growth hormone pulses to alter chromatin accessibility, as compared to the relative ineffectiveness of the more static pattern of growth hormone secretion in females. Supporting evidence is found in the impact of hypophysectomy and growth hormone treatment on chromatin accessibility, and the binding of specific transcription factors and epigenetic marks at STAT5-sensitive sites. This work uncovers mechanisms underlying sex differences in liver function and will be of broad interest to endocrinologists and hepatologists.

Reviewed by eLife