Article
Biochemistry & Molecular Biology
Clemence Claussin, Jacob Vazquez, Iestyn Whitehouse
Summary: This study developed a method called Replicon-seq, which can accurately define the movement of individual replisomes across the genome. Using this method, the study found that sister replisomes function autonomously and progress through chromatin with remarkable consistency. Replication forks pause briefly when encountering obstacles but quickly resume synthesis, and the helicase Rrm3 plays a critical role in mitigating the effect of protein barriers and facilitating efficient termination.
Article
Biochemistry & Molecular Biology
Ying Ni, Xudong Liu, Zemenu Mengistie Simeneh, Mengsu Yang, Runsheng Li
Summary: This study evaluates the application of the recently released R10.4 flow cell from Oxford Nanopore Technologies in human cancer genomics and epigenomic research. The results show that R10.4 performs better than R9.4.1 in terms of read accuracy, variant detection, methylation calling, and genome recovery rate. In addition, the study proposes a promising method for high-yield single-cell whole-genome amplification sequencing and provides a possible solution for filtering false positive sites using R10.4 data.
COMPUTATIONAL AND STRUCTURAL BIOTECHNOLOGY JOURNAL
(2023)
Review
Biochemistry & Molecular Biology
Xanita Saayman, Fumiko Esashi
Summary: DNA double-strand breaks can be toxic to the human genome and lead to premature aging, neurodegenerative disorders, and carcinogenesis. Recent advancements in sequencing technologies allow the systematic mapping of genome instability hotspots. These breakomes challenge the traditional paradigm of DNA breakage primarily occurring in hard-to-replicate regions and provide insights into biological mechanisms related to genome instability.
Article
Biology
Roman Jaksik, David A. A. Wheeler, Marek Kimmel
Summary: This study proposes a method of detecting ORI based on somatic mutation patterns caused by the mutator phenotype of damaged DNA polymerase epsilon (POLE), and identifies shared ORI locations in tumors through accumulated mutations. The study also compares the results from multiple detection methods and defines a consensus set of ORI. The results demonstrate the viability of mutation-based detection in determining ORI location and associated sequence features.
Article
Cell Biology
Chun-Yi Cho, James P. Kemp, Robert J. Duronio, Patrick H. O'Farrell
Summary: Collisions between DNA replication forks and transcribing RNA polymerases disrupt gene transcription, especially during the rapid cell cycles of early embryonic development. Replication dependency defers the onset of transcription to maintain orderly progression and avoid conflicts between transcription and replication.
Review
Biochemistry & Molecular Biology
Zhi-Xiong Zhou, Jessica S. Williams, Scott A. Lujan, Thomas A. Kunkel
Summary: Ribonucleotides are the most abundant non-canonical nucleotides in the genome, with significant influence on genome biology. Recent progress has been made in understanding their genomic presence, incorporation characteristics, and usefulness as biomarkers for polymerase enzymology. The discussion also covers ribonucleotide processing, genetic consequences of unrepaired ribonucleotides in DNA, and evidence supporting their transient presence in the nuclear genome.
CRITICAL REVIEWS IN BIOCHEMISTRY AND MOLECULAR BIOLOGY
(2021)
Article
Multidisciplinary Sciences
Yiwei He, Meghan V. Petrie, Haiyang Zhang, Jared M. Peace, Oscar M. Aparicio
Summary: Eukaryotic chromosomes have different replication timings, which are regulated by epigenetic mechanisms involving histone deacetylases. Histone deacetylase Sir2 negatively regulates replication initiation at multicopy rDNA origins, while Rpd3 histone deacetylase negatively regulates firing of single-copy origins. The effect of Rpd3 on single-copy origins may be indirect, mediated by its role in rDNA origin firing. Our experiments support the idea that origins compete for limiting factors, but Rpd3's effect on single-copy origins is independent of rDNA copy-number and Sir2's effects on rDNA origin firing.
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
(2022)
Article
Biochemistry & Molecular Biology
Gustavo Carvalho, Bruno Marcal Repoles, Isabela Mendes, Paulina H. Wanrooij
Summary: Research has focused on maintenance and instability of mitochondrial DNA, exploring the role of DNA repair factors in mitochondria and the connection between mtDNA damage and immune response. Future studies should delve into mechanisms by which mitochondria maintain mtDNA, the balance between repair and degradation, as well as the release of mtDNA into the cytosol.
ANTIOXIDANTS & REDOX SIGNALING
(2022)
Article
Infectious Diseases
Mohamed Amine Skhairia, Naira Dekhil, Besma Mhenni, Saloua Ben Fradj, Helmi Mardassi
Summary: The study identified two main clonal complexes within the L4.3/LAM sublineage in Tunisia, with TUN4.3_CC1 being the dominant group. TUN4.3_CC1 demonstrated higher genetic diversity and stability, suggesting a more ancient origin.
INTERNATIONAL JOURNAL OF INFECTIOUS DISEASES
(2021)
Review
Cell Biology
Scott Alexander Lujan, Thomas A. Kunkel
Summary: This study describes the contribution of DNA mismatch repair (MMR) to the stability of the eukaryotic nuclear genome determined by whole-genome sequencing. While mutation rates in wild-type nuclear genomes are known for over 40 eukaryotic species, fewer measurements have been done in mismatch repair-defective organisms, mainly focusing on Saccharomyces cerevisiae and human tumors. Well-studied organisms include Drosophila melanogaster and Mus musculus, while less genetically tractable species include great apes and long-lived trees. Various techniques have been developed to gather mutation rates per generation or per cell division, and mechanistic studies involving genetic manipulation of MMR genes have been limited to specific organisms like yeast, Arabidopsis thaliana, Caenorhabditis elegans, and one chicken cell line. The few MMR studies reported to date indicate a significant contribution of MMR to genome stability, providing insights that would have been impossible to obtain through reporter gene assays.
Article
Mathematics, Applied
Ting Xu, Ting-Zhu Huang, Liang-Jian Deng, Hong-Xia Dou, Naoto Yokoya
Summary: This paper proposes an algorithm based on defined scaled tri-factorization (STF) for fast and accurate tensor ring (TR) decomposition. The algorithm accurately represents various matrices while maintaining computational efficiency. Experimental results show that the proposed method is faster and more accurate than existing algorithms for TR decomposition and tensor train (TT) decomposition.
COMPUTATIONAL & APPLIED MATHEMATICS
(2023)
Article
Gastroenterology & Hepatology
Kaitao Zhao, Fangteng Guo, Jingjing Wang, Youquan Zhong, Junzhu Yi, Yan Teng, Zaichao Xu, Li Zhao, Aixin Li, Zichen Wang, Xinwen Chen, Xiaoming Cheng, Yuchen Xia
Summary: We investigated the process of HBV infection in murine hepatic cells and found that HBV cannot infect murine hepatic cells expressing hNTCP effectively. Moreover, we discovered that the disassembly of cytoplasmic HBV nucleocapsids is restricted in murine hepatic cells. Overcoming this limitation may help to establish an HBV infection mouse model.
Article
Plant Sciences
Alessia Russo, Baptiste Mayjonade, Daniel Frei, Giacomo Potente, Roman T. Kellenberger, Lea Frachon, Dario Copetti, Bruno Studer, Juerg E. Frey, Ueli Grossniklaus, Philipp M. Schluter
Summary: This article describes a method for extracting high molecular weight (HMW) DNA from low input plant material, which is easy to follow and quick. It successfully enables HMW DNA extraction from different plant species and is suitable for long-read sequencing on the Oxford Nanopore Technologies PromethION(R) platform.
FRONTIERS IN PLANT SCIENCE
(2022)
Review
Biochemical Research Methods
Dohun Yi, Jin-Wu Nam, Hyobin Jeong
Summary: Structural variants (SVs) are diverse genomic rearrangements that accumulate in the genome during cell development and aging, potentially impacting cancer development. Detecting somatic SVs is challenging but crucial for understanding their functional implications. This review summarizes recent advances in whole-genome sequencing (WGS)-based approaches for somatic SV detection, including computational algorithms for bulk WGS data and cutting-edge single-cell techniques. The advantages and limitations of bulk and single-cell approaches are discussed, along with their potential for linking somatic SVs to functional readouts.
BRIEFINGS IN BIOINFORMATICS
(2023)
Article
Chemistry, Physical
Mengbiao Guo, Zhou Songyang, Yuanyan Xiong
Summary: ChArmTelo is a computational toolbox for analyzing telomeres at the chromosome arm level in humans and other animals. It has been demonstrated to reveal population-specific differences in arm-level telomere lengths and identify liver cancer signatures. It also suggests that disruption of DNA replication origin may play a role in cancer by affecting telomere lengths.
Article
Oncology
Dean A. Regier, Brandon Chan, Sarah Costa, David W. Scott, Christian Steidl, Joseph M. Connors, Aly Karsan, Marco A. Marra, Robert Kridel, Ian Cromwell, Samantha Pollard
Summary: This study examined the cost-effectiveness of adding ibrutinib to the treatment of patients under the age of 60 with ABC-DLBCL. The analysis found that genetic testing to diagnose ABC-DLBCL and providing ibrutinib along with standard care treatment had a low to moderate probability of being cost-effective, depending on decision maker willingness to pay and the cost of the genetic test.
Meeting Abstract
Hematology
Nicole Thomas, Kostiantyn Dreval, Daniela S. Gerhard, Laura K. Hilton, Jeremy S. Abramson, Nancy L. Bartlett, Jeffrey Bethony, Jay Bowen, Anthony Bryan, Corey Casper, Maureen Dyer, Manel Esteller, Carlos Garcia-Prieto, Julie M. Gastier-Foster, Alina S. Gerrie, Bruno M. Grande, Timothy C. Greiner, Nicholas B. Griner, Thomas G. Gross, Nancy Lee Harris, John D. Irvin, Elaine S. Jaffe, Fabio Leal, Jean Paul Martin, Marie-Reine Martin, Sam M. Mbulaiteye, Charles G. Mullighan, Andrew J. Mungall, Karen Mungall, Constance Namirembe, Ariela Noy, Martin D. Ogwang, Jackson Orem, German Ott, Hilary Petrello, Steven J. Reynolds, Steven H. Swerdlow, Alexandra Traverse-Glehen, Wyndham H. Wilson, Marco A. Marra, Louis M. Staudt, David W. Scott, Ryan D. Morin
Article
Biochemical Research Methods
Pierre Bost, Daniel Schulz, Stefanie Engler, Clive Wasserfall, Bernd Bodenmiller
Summary: Recent advances in multiplexed imaging methods have allowed for simultaneous detection of multiple proteins and RNAs, providing a deeper understanding of the spatial characteristics of healthy and diseased tissues. However, optimal design parameters for multiplex imaging studies, particularly in capturing all cell phenotype clusters, are currently lacking. In this study, a statistical framework using a spatial transcriptomic atlas was developed to determine the number and area of fields of view needed to accurately identify all cell phenotypes in a tissue. This strategy, applied to imaging mass cytometry data, identified a measure of tissue spatial segregation that enables optimal experimental design, thus improving the design of multiplexed imaging studies.
Correction
Neurosciences
Mor Kenigsbuch, Pierre Bost, Shahar Halevi, Yuzhou Chang, Shuo Chen, Qin Ma, Renana Hajbi, Benno Schwikowski, Bernd Bodenmiller, Hongjun Fu, Michal Schwartz, Ido Amit
NATURE NEUROSCIENCE
(2023)
Article
Multidisciplinary Sciences
Sandra Tietscher, Johanna Wagner, Tobias Anzeneder, Claus Langwieder, Martin Rees, Bettina Sobottka, Natalie de Souza, Bernd Bodenmiller
Summary: Immune checkpoint therapy in breast cancer is limited to triple negative patients and shows rare long-term clinical benefit. This study explores the immune environments of human breast tumors with or without exhausted T cells, focusing on luminal subtypes. The presence of a PD-1(high) exhaustion-like T cell phenotype is associated with an inflammatory immune environment, increased myeloid cell activation, elevated immunomodulatory and cytokine signaling, accumulation of natural killer T cells, and altered spatial organization. PD-1 and CXCL13 expression on T cells, and MHC-I expression on tumor cells are distinguishing features between the immune environments.
NATURE COMMUNICATIONS
(2023)
Article
Oncology
Ossia M. Eichhoff, Corinne I. Stoffel, Jan Kasler, Luzia Briker, Patrick Turko, Gergely Karsai, Nina Zila, Verena Paulitschke, Phil F. Cheng, Alexander Leitner, Andrea Bileck, Nicola Zamboni, Anja Irmisch, Zsolt Balazs, Aizhan Tastanova, Susana Pascoal, Pal Johansen, Rebekka Wegmann, Julien Mena, Alaa Othman, Vasanthi S. Viswanathan, Judith Wenzina, Andrea Aloia, Annalisa Saltari, Andreas Dzung, Michael Krauthammer, Stuart L. Schreiber, Thorsten Hornemann, Martin Distel, Berend Snijder, Reinhard Dummer, Mitchell P. Levesque
Summary: The clinical management of NRAS-mutated melanomas is challenging due to resistance that arises through genetic, transcriptional, and metabolic adaptation. However, the adoption of a mesenchymal phenotype with a quiescent metabolic program in NRAS-mutated melanoma cells confers sensitivity to reactive oxygen species (ROS) induction, which can be inhibited by ROS inducers in combination with MAPK pathway inhibitors. The findings suggest that targeting both metabolic reprogramming and MAPK signaling could improve patient treatment in melanoma and other cancers.
Article
Biochemistry & Molecular Biology
E. Titmuss, K. Milne, M. R. Jones, T. Ng, J. T. Topham, S. D. Brown, D. F. Schaeffer, S. Kalloger, D. Wilson, R. D. Corbett, L. M. Williamson, K. Mungall, A. J. Mungall, R. A. Holt, B. H. Nelson, S. J. M. Jones, J. Laskin, H. J. Lim, M. A. Marra
Summary: The POG program at BC Cancer identified specific alterations in colorectal cancer using whole genome and transcriptome analysis, and successfully treated a patient with irbesartan, an antihypertensive drug, resulting in a profound and durable response. Analysis showed an increase in immune signaling and infiltrating immune cells, particularly CD8+ T cells, in the relapsed tumor, suggesting an activated immune response contributed to the anti-tumor effect.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2023)
Article
Multidisciplinary Sciences
Seong-Hwan Jun, Hosein Toosi, Jeff Mold, Camilla Engblom, Xinsong Chen, Ciara O'Flanagan, Michael Hagemann-Jensen, Rickard Sandberg, Samuel Aparicio, Johan Hartman, Andrew Roth, Jens Lagergren
Summary: Functional characterization of cancer clones is important for understanding cancer's evolutionary mechanisms. The authors introduce PhylEx, a method that combines bulk genomics and single-cell RNA sequencing data to reconstruct clonal trees and identify clones. PhylEx outperforms other methods and allows for accurate inference of clonal trees and analysis of cancer.
NATURE COMMUNICATIONS
(2023)
Article
Hematology
Sanam Shahid, Nicholas Ceglia, Jean-Benoit Le Luduec, Andrew Mcpherson, Barbara Spitzer, Theodota Kontopoulos, Viktoria Bojilova, M. Kazim Panjwani, Mikhail Roshal, Sohrab P. Shah, Omar Abdel-Wahab, Benjamin Greenbaum, Katharine C. Hsu
Summary: This study investigated the effects of allo-HCT on AML cells using a novel single-cell proteogenomic approach. The results demonstrated immune-related transcriptional signatures in posttransplant relapses, revealing dysfunction in activated natural killer cells and CD8+ T-cell subsets, as well as an expansion of dysfunctional T cells.
Article
Cell Biology
Jana Raja Fischer, Hartland Warren Jackson, Natalie de Souza, Zsuzsanna Varga, Peter Schraml, Holger Moch, Bernd Bodenmiller
Summary: Although breast cancer mortality is caused by metastasis, clinical decisions are not based on the phenotype of disseminated cells. This study compares single-cell phenotypes of primary breast tumors and matched lymph node metastases using multiplex imaging mass cytometry. The researchers observe extensive phenotypic variability between primary and metastatic sites, and identify single-cell phenotypes and spatial organizations of disseminated tumor cells associated with patient survival. They also find that p53 and GATA3 in lymph node metastases provide prognostic information beyond clinical classifiers.
CELL REPORTS MEDICINE
(2023)
Article
Multidisciplinary Sciences
Nicholas Ceglia, Zachary Sethna, Samuel S. Freeman, Florian Uhlitz, Viktoria Bojilova, Nicole Rusk, Bharat Burman, Andrew Chow, Sohrab Salehi, Farhia Kabeer, Samuel Aparicio, Benjamin D. Greenbaum, Sohrab P. Shah, Andrew McPherson
Summary: To decipher individual cell phenotypes, high dimensional single-cell RNA sequencing is required. GeneVector is a scalable framework that uses gene co-expression to perform dimensionality reduction, allowing for the identification of transcriptional programs and cell type classification. GeneVector has been shown to capture phenotype-specific pathways and identify pathway variation in response to treatment.
NATURE COMMUNICATIONS
(2023)
Letter
Clinical Neurology
Catherine Wainwright, Steve Fuller, Victoria Dickinson, Wendy Greenwood
Summary: This study analyzed the content of fingolimod in three FDA approved generic capsule products and found significant variation between manufacturers. One of the products had a fingolimod content of only 76.8% of the approved dose, falling below the FDA acceptance criteria.
MULTIPLE SCLEROSIS AND RELATED DISORDERS
(2023)
Article
Multidisciplinary Sciences
Yi Cui, Gaojie Yang, Daniel R. Goodwin, Ciara H. O'Flanagan, Anubhav Sinha, Chi Zhang, Kristina E. Kitko, Tay Won Shin, Demian Park, Samuel Aparicio, Edward S. Boyden
Summary: Expansion microscopy (ExM) enlarges specimens physically for nanoimaging on standard light microscopes. The multifunctional anchor simplifies ExM protocols, reduces cost, and enables the preservation and visualization of RNA transcripts, proteins, and other biomolecular species.
Article
Oncology
Luca Licata, Marco Barreca, Barbara Galbardi, Matteo Dugo, Giulia Viale, Balazs Gyorffy, Thomas Karn, Lajos Pusztai, Luca Gianni, Maurizio Callari, Giampaolo Bianchini
Summary: Luminal breast cancers with high proliferation and low ER signaling have poor prognosis. These tumors show high response to chemotherapy, but resistance to endocrine therapy and palbociclib. Immunotherapy may play a potential role in treating these tumors.
BRITISH JOURNAL OF CANCER
(2023)
Article
Multidisciplinary Sciences
Ha-Linh Nguyen, Tatjana Geukens, Marion Maetens, Samuel Aparicio, Ayse Bassez, Ake Borg, Jane Brock, Annegien Broeks, Carlos Caldas, Fatima Cardoso, Maxim De Schepper, Mauro Delorenzi, Caroline A. Drukker, Annuska M. Glas, Andrew R. Green, Edoardo Isnaldi, Jorunn Eyfjoro, Hazem Khout, Stian Knappskog, Savitri Krishnamurthy, Sunil R. Lakhani, Anita Langerod, John W. M. Martens, Amy E. McCart Reed, Leigh Murphy, Stefan Naulaerts, Serena Nik-Zainal, Ines Nevelsteen, Patrick Neven, Martine Piccart, Coralie Poncet, Kevin Punie, Colin Purdie, Emad A. Rakha, Andrea Richardson, Emiel Rutgers, Anne Vincent-Salomon, Peter T. Simpson, Marjanka K. Schmidt, Christos Sotiriou, Paul N. Span, Kiat Tee Benita Tan, Alastair Thompson, Stefania Tommasi, Karen Van Baelen, Marc Van de Vijver, Steven Van Laere, Laura van't Veer, Giuseppe Viale, Alain Viari, Hanne Vos, Anke T. Witteveen, Hans Wildiers, Giuseppe Floris, Abhishek D. Garg, Ann Smeets, Diether Lambrechts, Elia Biganzoli, Francois Richard, Christine Desmedt
Summary: Obesity is associated with an increased risk of developing breast cancer and worse prognosis in breast cancer patients. This study investigates the biological differences in untreated primary breast cancer according to patients' body mass index (BMI). The study finds several genomic alterations that are differentially prevalent in overweight or obese patients compared to lean patients. It also reveals an elevated and unresolved inflammation of the breast cancer tumor microenvironment associated with obesity. The findings suggest that patient adiposity may play a significant role in the heterogeneity of breast cancer and should be considered for tailored treatment.
NATURE COMMUNICATIONS
(2023)
