Genomics

Is tumor mutational burden predictive of response to immunotherapy?

1. Carino Gurjao
2. Dina Tsukrov
3. Maxim Imakaev
4. Lovelace J Luquette
5. Leonid A Mirny

• Curated by eLife

  eLife Assessment

  This useful study examines relationships between tumor mutational burden and the response to immunotherapy, using new data sets along with publicly available data sets. The authors conclude that tumor mutational burden cut-offs are unreliable proxies for predicting the response to therapy, underpinned by solid evidence, but with several caveats and assumptions that leave the central question subject to further inquiry. In summary, this is an interesting study that adds to a growing body of work investigating the particular conditions governing the effectiveness of immunotherapy.

Reviewed by eLife

Increased inflammatory signature in myeloid cells of non-small cell lung cancer patients with high clonal hematopoiesis burden

1. Hyungtai Sim
2. Hyun Jung Park
3. Geun-Ho Park
4. Yeon Jeong Kim
5. Woong-Yang Park
6. Se-Hoon Lee
7. Murim Choi

• Curated by eLife

  eLife Assessment

  This valuable article represents a significant body of work that addresses some novel aspects of the biology of lung cancer, the overall influence of CHIP and its impacts on responses to therapy. While a high clonal hematopoiesis (CHIP) burden was previously linked with an inflammatory phenotype in other disease settings, the authors demonstrate with solid evidence that this is also true for lung cancer. CHIP is complex and more data will be required to substantiate more evidence with regard perhaps to specific mutations in certain situations and how this might influence therapy choices.

Reviewed by eLife

Functional characteristics and computational model of abundant hyperactive loci in the human genome

1. Sanjarbek Hudaiberdiev
2. Ivan Ovcharenko

• Curated by eLife

  eLife Assessment

  This valuable study explores the sequence characteristics and conservation of high-occupancy target loci, regions in the human genome such as promoters and enhancers that are bound by a multitude of transcription factors. The computational analyses presented in this study are solid. This study would be a helpful resource for researchers performing ChIP-seq based analyses of transcription factor binding.

Reviewed by eLife

Expression of most retrotransposons in human blood correlates with biological aging

1. Yi-Ting Tsai
2. Nogayhan Seymen
3. I Richard Thompson
4. Xinchen Zou
5. Warisha Mumtaz
6. Sila Gerlevik
7. Ghulam J Mufti
8. Mohammad M Karimi

• Curated by eLife

  eLife Assessment

  The study by Tsai et al. employed multi-omics approaches, including transcriptomic, methylomic, and single-cell RNA-seq, and provided a solid and comprehensive analysis of the correlation between retrotransposable element (RTE) expression and biological aging in human blood. Their findings highlight the differential roles of RTE families, providing valuable insights for understanding the mechanisms of human aging.

Reviewed by eLife

High-speed whole-genome sequencing of a Whippet: Rapid chromosome-level assembly and annotation of an extremely fast dog’s genome

1. Marcel Nebenführ
2. David Prochotta
3. Alexander Ben Hamadou
4. Axel Janke
5. Charlotte Gerheim
6. Christian Betz
7. Carola Greve
8. Hanno Jörn Bolz

• Curated by GigaByte

  Editors Assessment:

  This Data Release paper presents the genome of the whippet breed of dog. Demonstrating a streamlined laboratory and bioinformatics workflows with PacBio HiFi long-read whole-genome sequencing that enables the generation of a high-quality reference genome within one week. The genome study being a collaboration between an academic biodiversity institute and a medical diagnostic company. The presented method of working and workflow providing examples that can be used for a wide range of future human and non-human genome projects. The final is 2.47 Gbp assembly being of high quality - with a contig N50 of 55 Mbp and a scaffold N50 of 65.7 Mbp. This reference being scaffolded into 39 chromosome-length scaffolds and the annotation resulting in 28,383 transcripts. The results also looked at the Myostatin gene which can be used for breeding purposes, as these heterozygous animals can have an advantage in dog races. The reviewers making the authors clarify this part a little better with additional results. Overall this study demonstrating how rapidly animal genome research can be carried out through close and streamlined time management and collaboration.

  This evaluation refers to version 1 of the preprint

Reviewed by GigaByte

Transcriptomic profiling of Schlemm’s canal cells reveals a lymphatic-biased identity and three major cell states

1. Revathi Balasubramanian
2. Krishnakumar Kizhatil
3. Taibo Li
4. Nicholas Tolman
5. Aakriti Bhandari
6. Graham Clark
7. Violet Bupp-Chickering
8. Ruth A Kelly
9. Sally Zhou
10. John Peregrin
11. Marina Simón
12. Christa Montgomery
13. W Daniel Stamer
14. Jiang Qian
15. Simon WM John

• Curated by eLife

  eLife assessment

  This valuable study has characterized the unique expression of Schlemm's canal endothelial cells (SECs) using FACS-sorted specific cell bulk RNA-Seq and scRNA-/snRNA-Seq of mouse SECs. The compelling study identified novel biomarkers for SECs and molecular markers for two inner wall SEC states and outwall SECs in mouse eyes. Significant gene networks and pathways were elucidated for their potential contribution to glaucoma pathogenesis, providing targets for further research in relation to glaucoma.

Reviewed by eLife

Interchromosomal segmental duplication drives translocation and loss of P. falciparum histidine-rich protein 3

1. Nicholas J Hathaway
2. Isaac E Kim
3. Neeva WernsmanYoung
4. Sin Ting Hui
5. Rebecca Crudale
6. Emily Y Liang
7. Christian P Nixon
8. David Giesbrecht
9. Jonathan J Juliano
10. Jonathan B Parr
11. Jeffrey A Bailey

• Curated by eLife

  eLife assessment

  This work provides important insight into the mechanisms of hrp2 and particularly hrp3 deletion generation. The generation of additional long-read data alongside a new analysis of 19,000 public short-read sequenced genomes makes this the most detailed investigation currently available on this topic, which has high public health importance and also basic biological interest. The revised version of the manuscript provides convincing evidence for the proposed mechanisms.

Reviewed by eLife

Genome-wide mapping of native co-localized G4s and R-loops in living cells

1. Ting Liu
2. Xing Shen
3. Yijia Ren
4. Hongyu Lu
5. Yu Liu
6. Chong Chen
7. Lin Yu
8. Zhihong Xue

• Curated by eLife

  eLife assessment

  This study describes a useful antibody-free method to map both G-quadruplexes and R-loops in vertebrate cells independently of the BG4 and S9.6 antibodies. It also reveals that the helicase Dhx9 can affect the self-renewal and differentiation capacities of mESCs, perhaps by regulating co-localized G4s and R-loops. The datasets provided might constitute a good starting point for future functional studies, and although the strength of the evidence that DHX9 interferes with the ability of mESCs to differentiate by regulating directly the stability of either G4s or R-loops has been improved compared to a previous version, it is still incomplete.

Reviewed by eLife

Regulatory genome annotation of 33 insect species

1. Hasiba Asma
2. Ellen Tieke
3. Kevin D Deem
4. Jabale Rahmat
5. Tiffany Dong
6. Xinbo Huang
7. Yoshinori Tomoyasu
8. Marc S Halfon

• Curated by eLife

  eLife assessment

  In the revised version of this important study, the authors present a convincing pipeline for insect genome regulatory annotation across 33 insect genomes spanning 5 orders. Despite technical limitations in the field owing to the lack of comprehensive knowledge of enhancer content in any system, the authors employ several independent downstream analyses to support the validity of their enhancer predictions for a subset of these genomes. Taken together, the revised results suggest that this prediction pipeline may have uses in identifying functional enhancers across large phylogenetic distances. Reviewers note caveats that an experimental validation is not yet available in the field to validate a large class of newly identified enhancers across such evolutionary distances, and other pipelines might be of use to compare. This work will be of interest to the computational genomics, evolutionary biology, and gene regulation fields.

Reviewed by eLife

Robustness and reliability of single-cell regulatory multi-omics with deep mitochondrial mutation profiling

1. Chen Weng
2. Jonathan S. Weissman
3. Vijay G. Sankaran

Reviewed by Arcadia Science