Genomics

Activity of MukBEF for chromosome management in E. coli and its inhibition by MatP

1. Mohammed Seba
2. Frederic Boccard
3. Stéphane Duigou

• Curated by eLife

  eLife assessment

  This important work combines DNA contact analysis and controlled genome rearrangements to investigate the processes that organize the E. coli chromosome, with a particular focus on how the SMC-related complex MukBEF is regulated. The evidence supporting the conclusions is compelling, with time-resolved experiments and analysis of mutant strains. The work will be of broad interest to chromosome biologists and bacterial cell biologists.

Reviewed by eLife

Integrative analysis of DNA replication origins and ORC-/MCM-binding sites in human cells reveals a lack of overlap

1. Mengxue Tian
2. Zhenjia Wang
3. Zhangli Su
4. Etsuko Shibata
5. Yoshiyuki Shibata
6. Anindya Dutta
7. Chongzhi Zang

• Curated by eLife

  eLife assessment

  The paper addresses the mechanism of initiation of DNA replication in human cells by analyzing published data on the location of origins of DNA replication and the location of binding sites in the genome for ORC and MCM2-7 complexes. There are some useful analyses of existing data but there are concerns regarding the conclusion that there might be alternative mechanisms for determining the location of origins of DNA replication in human cells compared to the well known mechanism known from many eukaryotic systems, including yeast, Xenopus, C. elegans and Drosophila. The lack of overlap between binding sites for ORC1 and ORC2, which are known to form a complex in human cells, is a particular concern and points to the evidence for the accurate localization of their binding sites in the genome being incomplete.

Reviewed by eLife

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

The Genomic Legacy of Human Management and sex-biased Aurochs hybridization in Iberian Cattle

1. Torsten Günther
2. Jacob Chisausky
3. M. Ángeles Galindo-Pellicena
4. Eneko Iriarte
5. Oscar Cortes Gardyn
6. Paulina G. Eusebi
7. Rebeca García-González
8. Irene Urena
9. Marta Moreno
10. Alfonso Alday
11. Manuel Rojo
12. Amalia Pérez
13. Cristina Tejedor Rodríguez
14. Iñigo García Martínez de Lagrán
15. Juan Luis Arsuaga
16. José-Miguel Carretero
17. Anders Götherström
18. Colin Smith
19. Cristina Valdiosera

• Curated by eLife

  eLife assessment

  Using genomic data from ancient and modern samples, this important study investigates the genomic history of cattle in Iberia, focusing on the admixture between domestic cattle and their wild ancestors, aurochs. The authors present solid evidence for interbreeding between domestic cattle and wild aurochs since the Neolithic period, although the extent, sex bias, and directionality of genetic flow over time remain highly unclear. The authors also show that the aurochs ancestry in cattle stabilized at ~20% since ~4000 years ago and continues into modern breeds, including the Lidia breed that is bred for aggressiveness and used in bullfighting. The work will be of interest to evolutionary biologists and quantitative geneticists who seek to understand the genomic history and genetic basis of trait variation of domesticated animals.

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

Human-specific lncRNAs contributed critically to human evolution by distinctly regulating gene expression

1. Jie Lin
2. Yujian Wen
3. Ji Tang
4. Xuecong Zhang
5. Huanlin Zhang
6. Hao Zhu

• Curated by eLife

  eLife assessment

  This valuable study uses population and functional genomics to examine long non-coding RNAs (lncRNAs) in the context of human evolution. Computational prediction of human-specific lncRNAs and their DNA binding sites and analyses of these loci lead to the development of hypotheses regarding the potential roles of these genetic elements in human biology. The evidence supporting the conclusions is, however, still incomplete, as key details regarding the methodology and analyses are lacking.

Reviewed by eLife

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