Article
Immunology
Chenshen Huang, Na Zhang, Hao Xiong, Ning Wang, Zhizhong Chen, Zhizhan Ni, Xiaohong Liu, Boxu Lin, Bujun Ge, Bing Du, Qi Huang
Summary: This study aims to explore a novel method for transcriptional regulation and proposes a new pipeline for analyzing the role of GPRC5B in COAD. By using RNA-seq, ATAC-seq, and ChIP-seq, researchers found the correlation between GPRC5B and macrophages and identified TF GATA4 as a key upstream factor.
FRONTIERS IN IMMUNOLOGY
(2022)
Article
Biochemical Research Methods
Maria Osmala, Gokcen Eraslan, Harri Lahdesmaki
Summary: ChromDMM is a mixture model based on multiple chromatin features, which accurately clusters genomic regions and discovers distinctive patterns of epigenetic signals at regulatory elements. Validated with simulated data and ENCODE data, ChromDMM demonstrates higher accuracy and robustness.
Article
Developmental Biology
Julie Gamart, Iros Barozzi, Frederic Laurent, Robert Reinhardt, Laurene Ramos Martins, Thomas Oberholzer, Axel Visel, Rolf Zeller, Aimee Zuniga
Summary: SMAD4 regulates gene expression in early limb buds, primarily mediating BMP signal transduction and playing a crucial role in upregulating target genes in anterior limb bud mesenchyme, while also repressing posterior gene expression. This study reveals opposing trans-regulatory inputs from SHH- and SMAD4-mediated BMP signal transduction during digit patterning and outgrowth in early limb buds.
Article
Biochemistry & Molecular Biology
Young-Im Kim, Yu-Chou Tseng, Gamze Ayaz, Shasha Wang, Hualong Yan, Wendy du Bois, Howard Yang, Tao Zhen, Maxwell P. P. Lee, Paul Liu, Rosandra N. Kaplan, Jing Huang
Summary: This study identifies SOX9 as a critical transcription factor induced by RUNX2 in osteosarcoma cells. The activation of MYC, a downstream target of RUNX2, is mediated by SOX9. The interaction between SOX9 and chromatin factor JMJD1C is also demonstrated, showing that depletion of JMJD1C impairs osteosarcoma tumor growth.
CELL AND BIOSCIENCE
(2023)
Article
Multidisciplinary Sciences
Sebastien Bastide, Elad Chomsky, Baptiste Saudemont, Yann Loe-Mie, Sandrine Schmutz, Sophie Novault, Heather Marlow, Amos Tanay, Francois Spitz
Summary: We developed a spatially resolved single-cell transcriptomics method to explore the genetic programs underlying the emergence of specialized cell types during mouse limb development. Our study revealed two parallel regulatory systems and demonstrated the complex multiscale reorganization of the embryonic limb upon perturbation of its spatial organizing centers.
Article
Biochemistry & Molecular Biology
Yuyun Zhang, Zijuan Li, Yu'e Zhang, Kande Lin, Yuan Peng, Luhuan Ye, Yili Zhuang, Meiyue Wang, Yilin Xie, Jingyu Guo, Wan Teng, Yiping Tong, Wenli Zhang, Yongbiao Xue, Zhaobo Lang, Yijing Zhang
Summary: The majority of transcription factor binding sites in the wheat genome are embedded in transposable elements, contributing to adaptive evolution. Some non-transposable element derived binding sites share high sequence similarity with transposable element embedded sites, potentially originating from Triticeae-specific transposable elements. Transposable element-derived binding sites are linked to wheat-specific gene responses, indicating they play a crucial role in driving regulatory innovations.
Article
Oncology
Franziska Liss, Miriam Frech, Ying Wang, Gavin Giel, Sabrina Fischer, Clara Simon, Lisa Marie Weber, Andrea Nist, Thorsten Stiewe, Andreas Neubauer, Andreas Burchert, Robert Liefke
Summary: The study identified the transcription factor IRF8 as a novel AML-specific susceptibility gene in humans, demonstrating its critical role in regulating key signaling molecules, cell proliferation, and patient prognosis. High IRF8 expression is associated with poorer outcomes, indicating IRF8 as a potential biomarker and molecular target for a subset of AML cases.
Article
Genetics & Heredity
Daian Pan, Jinghong Zhong, Jingcheng Zhang, Haisi Dong, Daqing Zhao, He Zhang, Baojin Yao
Summary: This study aims to reveal the influence of Nfix on the proliferation and differentiation of chondrocytes, and to explore its potential action mechanism. The results showed that Nfix overexpression promoted extracellular matrix (ECM) synthesis in chondrocytes, while silencing inhibited it. Furthermore, Nfix exerted a positive regulatory effect on Sox9, which may promote chondrocyte proliferation and inhibit differentiation. These findings suggest that Nfix may be a potential target for the regulation of chondrocyte proliferation and differentiation.
Article
Immunology
Chuanxin Shi, Shuli Wang, Jincheng Han, Li Xi, Min Li, Zhiqiang Li, Hui Zhang
Summary: The ArsR family transcription factors play a crucial role in regulating the adaptation of Brucella to environmental changes and their virulence. This study identified the direct targets of the ArsR6 transcriptional regulator in Brucella and demonstrated its importance in survival and inflammatory response modulation in macrophages.
MICROBIAL PATHOGENESIS
(2022)
Article
Cell Biology
Yingchun Chen, Rongquan He, Zhiqiang Han, Yanyan Wu, Qiuyan Wang, Xiujuan Zhu, Zhiguang Huang, Juan Ye, Yao Tang, Hongbin Huang, Jianxu Chen, Hong Shan, Fei Xiao
Summary: ATF4 and CTCF were found to cooperatively control adipogenesis and adipose development by orchestrating transcription of adipogenic genes, revealing novel therapeutic targets in obesity treatment.
CELL BIOLOGY AND TOXICOLOGY
(2022)
Article
Biology
Russell Julian, Ryan M. Patrick, Ying Li
Summary: This study reveals the close relationship between dynamic chromatin modifications and gene regulation in response to environmental stimuli in plants, with organ-specific differences.
COMMUNICATIONS BIOLOGY
(2023)
Article
Genetics & Heredity
David Rodriguez-Crespo, Magali Nanchen, Shweta Rajopadhye, Chantal Wicky
Summary: The research identifies LSL-1 as a crucial transcriptional regulator for germline genes in C. elegans, playing a key role in the development of germline cells. LSL-1 acts as a transcriptional activator for germline genes involved in various processes such as homologous chromosome pairing, recombination, and genome stability. Furthermore, LSL-1 functions by antagonizing the action of certain heterochromatin proteins involved in the repression of germline genes in somatic cells.
Article
Multidisciplinary Sciences
Shengen Shawn Hu, Lin Liu, Qi Li, Wenjing Ma, Michael J. Guertin, Clifford A. Meyer, Ke Deng, Tingting Zhang, Chongzhi Zang
Summary: The authors develop a computational model, SELMA, to estimate and correct enzymatic cleavage biases in chromatin accessibility profiling data. SELMA accurately estimates the biases from both bulk and single-cell DNase-seq and ATAC-seq data, and improves transcription factor binding inference and cell clustering in single-cell ATAC-seq data. SELMA enhances the analysis of chromatin accessibility sequencing data.
NATURE COMMUNICATIONS
(2022)
Article
Oncology
Tesa M. Severson, Yanyun Zhu, Angelo M. De Marzo, Tracy Jones, Jonathan W. Simons, William G. Nelson, Srinivasan Yegnasubramanian, Matthew L. Freedman, Lodewyk Wessels, Andries M. Bergman, Michael C. Haffner, Wilbert Zwart
Summary: The study investigated the epigenomic landscape of prostate cancer drivers in four clonal metastatic tumors from a single patient, revealing a core transcriptional program in clonal metastatic prostate cancer despite differences in the AR cistrome. Shared AR binding sites among healthy prostate, primary prostate cancer, and metastatic tumors signify core AR-driven transcriptional regulation within the prostate cell lineage.
MOLECULAR ONCOLOGY
(2021)
Article
Biotechnology & Applied Microbiology
Rhys Newell, Richard Pienaar, Brad Balderson, Michael Piper, Alexandra Essebier, Mikael Boden
Summary: Chromatin immunoprecipitation followed by sequencing (ChIP-seq) is a primary protocol for detecting DNA-protein interactions, and the adapted ChIP-R method statistically evaluates reproducibility from experimental replicates, improving the identification of transcription factor binding events. By re-analyzing existing datasets, ChIP-R can reconstruct reproducible peaks from fragments with enhanced biological enrichment compared to current strategies.
Article
Oncology
Irene S. Yu, Kathleen Wee, Laura Williamson, Emma Titmuss, Jianghong An, Sheida Naderi-Azad, Corey Metcalf, Stephen Yip, Basil Horst, Steven J. M. Jones, Katherine Paton, Brad H. Nelson, Marco Marra, Janessa J. Laskin, Kerry J. Savage
Summary: The case report describes a 66-year-old woman with metastatic uveal melanoma who showed an exceptional treatment response to ipilimumab/nivolumab therapy. The patient had almost complete resolution of metastatic disease, except for partial regression in one liver metastasis. Whole-genome and transcriptome analysis revealed genetic alterations in T-cell responses and high levels of plasma cells in the tumor microenvironment. The patient also had several germline SNPs that may have contributed to the treatment response and development of vitiligo. Elevated BMI and vitiligo may be clinically relevant factors for predicting response to immune checkpoint inhibitor therapy in uveal melanoma.
Article
Biotechnology & Applied Microbiology
Rahul Arora, Logan Haynes, Mehul Kumar, Reid McNeil, Jahanshah Ashkani, Steven C. Nakoneshny, T. Wayne Matthews, Shamir Chandarana, Robert D. Hart, Steven J. M. Jones, Joseph C. Dort, Doha Itani, Ayan Chanda, Pinaki Bose
Summary: There is a lack of prognostic biomarkers and targeted therapeutics for oral squamous cell carcinoma (OSCC). However, amplification of the chromosomal segment 3q22-3q29 is observed in many epithelial cancers, including OSCC. Through an integrative analysis, we identified NCBP2 and TFRC as potential prognostic biomarkers for HPV-negative OSCC, and showed that NCBP2 depletion can inhibit OSCC cell proliferation, migration, and invasion.
CANCER GENE THERAPY
(2023)
Article
Oncology
Geoffrey A. Pettitt, Carolyn D. Hurst, Zubeda Khan, Helen R. McPherson, Matthew C. Dunning, Olivia Alder, Fiona M. Platt, Emma V. Black, Julie E. Burns, Margaret A. Knowles
Summary: Resistance to FGFR inhibitors is common in bladder cancer, and various molecular profiles and mechanisms contribute to this resistance. Personalized therapy for FGFR-driven cancers is challenging due to the heterogeneity in resistance mechanisms and the persistence of resistant cell populations.
JOURNAL OF PATHOLOGY
(2023)
Article
Biochemistry & Molecular Biology
Kilannin Krysiak, Arpad M. Danos, Jason Saliba, Joshua F. McMichael, Adam C. Coffman, Susanna Kiwala, Erica K. Barnell, Lana Sheta, Cameron J. Grisdale, Lynzey Kujan, Shahil Pema, Jake Lever, Sarah Ridd, Nicholas C. Spies, Veronica Andric, Andreea Chiorean, Damian T. Rieke, Kaitlin A. Clark, Caralyn Reisle, Ajay C. Venigalla, Mark Evans, Payal Jani, Hideaki Takahashi, Avila Suda, Peter Horak, Deborah Ritter, Xin Zhou, Benjamin J. Ainscough, Sean Delong, Chimene Kesserwan, Mario Lamping, Haolin Shen, Alex R. Marr, My H. Hoang, Kartik Singhal, Mariam Khanfar, Brian Li, Wan-Hsin Lin, Panieh Terraf, Laura B. Corson, Yasser Salama, Katie M. Campbell, Kirsten M. Farncombe, Jianling Ji, Xiaonan Zhao, Xinjie Xu, Rashmi Kanagal-Shamanna, Ian King, Kelsy C. Cotto, Zachary L. Skidmore, Jason R. Walker, Jinghui Zhang, Aleksandar Milosavljevic, Ronak Y. Patel, Rachel H. Giles, Raymond H. Kim, Lynn M. Schriml, Elaine R. Mardis, Steven J. M. Jones, Gordana Raca, Shruti Rao, Subha Madhavan, Alex H. Wagner, Malachi Griffith, Obi L. Griffith
Summary: CIVIC is a crowd-sourced, public domain knowledgebase that provides literature-derived evidence characterizing the clinical utility of cancer variants. It supports variant interpretation guidelines, increases interoperability with other variant resources, and promotes widespread dissemination of structured curated data. It currently includes over 300 contributors and represents >3200 variants in >470 genes from >3100 publications.
NUCLEIC ACIDS RESEARCH
(2023)
Article
Biochemistry & Molecular Biology
Katherine Dixon, Yaoqing Shen, Kieran O'Neill, Karen L. L. Mungall, Simon Chan, Steve Bilobram, Wei Zhang, Marjorie Bezeau, Alshanee Sharma, Alexandra Fok, Andrew J. J. Mungall, Richard Moore, Ian Bosdet, My Linh Thibodeau, Sophie Sun, Stephen Yip, Kasmintan A. A. Schrader, Steven J. M. Jones
Summary: Nanopore long-read sequencing accurately detects pathogenic copy number alterations in cancer susceptibility genes and reveals unforeseen allelic heterogeneity and mechanisms of recurrent deletions. Integrating read-based and statistical phasing helps define extended haplotypes associated with founder alleles. Long-read sequencing is a sensitive method for characterizing private, recurrent and founder structural variants underlying breast cancer susceptibility.
EUROPEAN JOURNAL OF HUMAN GENETICS
(2023)
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)
Review
Gastroenterology & Hepatology
Jeremy Lotto, Tabea L. Stephan, Pamela A. Hoodless
Summary: Advancements in single-cell technologies and lineage tracing have enhanced our understanding of liver development. This review explores the formation of different types of liver cells and highlights the similarities between early liver development and the pathogenesis of liver injury. The research has significantly advanced our knowledge of cell differentiation, fate decisions, and the signaling microenvironment in liver development. This understanding also provides insights into liver disease and cancer and offers potential for improving regenerative medicine strategies.
NATURE REVIEWS GASTROENTEROLOGY & HEPATOLOGY
(2023)
Article
Oncology
Hiba K. Omairi, Cameron J. Grisdale, Mathieu Meode, Alexandra K. Bohm, Sophie Black, Nancy J. Adam, Cassidy P. Chapman, Tatiana Maroilley, John J. Kelly, Maja Tarailo-Graovac, Steven J. M. Jones, Michael D. Blough, John Gregory Cairncross
Summary: This study reveals that PDGFA fails to induce the expression of kinetochore and spindle assembly checkpoint genes, leading to defective mitosis in neural progenitor cells (NPCs). Surviving cells with unstable genomes accumulate chromosomal rearrangements and give rise to tumorigenic NPCs with recurrent gains and losses of chromosomal regions. This work provides new insights into the mechanisms underlying the development of glioblastoma.
Article
Biochemistry & Molecular Biology
Zhiping Li, Xuanmao Jiao, A. Gordon Robertson, Gabriele Di Sante, Anthony W. Ashton, Agnese DiRocco, Min Wang, Jun Zhao, Sankar Addya, Chenguang Wang, Peter A. McCue, Andrew P. South, Carlos Cordon-Cardo, Runzhi Liu, Kishan Patel, Rasha Hamid, Jorim Parmar, James B. DuHadaway, Steven J. M. Jones, Mathew C. Casimiro, Nikolaus Schultz, Andrew Kossenkov, Lai Yee Phoon, Hao Chen, Li Lan, Yunguang Sun, Kenneth A. Iczkowski, Hallgeir Rui, Richard G. Pestell
Summary: Prostate cancer, the second leading cause of death in American men, is found to be associated with the deletion of DACH1 gene, which may define a specific subtype of the disease requiring tailored therapies.
Article
Multidisciplinary Sciences
Ana Nikolic, Francesca Maule, Anna Bobyn, Katrina Ellestad, Seungil Paik, Sajid A. Marhon, Parinaz Mehdipour, Xueqing Lun, Huey-Miin Chen, Claire Mallard, Alexander J. Hay, Michael J. Johnston, Christopher J. Gafuik, Franz J. Zemp, Yaoqing Shen, Nicoletta Ninkovic, Katalin Osz, Elodie Labit, N. Daniel Berger, Duncan K. Brownsey, John J. Kelly, Jeff Biernaskie, Peter B. Dirks, Darren J. Derksen, Steven J. M. Jones, Donna L. Senger, Jennifer A. Chan, Douglas J. Mahoney, Daniel D. De Carvalho, Marco Gallo
Summary: The histone variant macroH2A2 controls an epigenetic mechanism of self-renewal and suggests new treatment approaches for glioblastoma patients.
NATURE COMMUNICATIONS
(2023)
Article
Genetics & Heredity
Eric B. Rondeau, Kris A. Christensen, David R. Minkley, Jong S. Leong, Michelle T. T. Chan, Cody A. Despins, Anita Mueller, Dionne Sakhrani, Carlo A. Biagi, Quentin Rougemont, Eric Normandeau, Steven J. M. Jones, Robert H. Devlin, Ruth E. Withler, Terry D. Beacham, Kerry A. Naish, Jose M. Yanez, Roberto Neira, Louis Bernatchez, William S. Davidson, Ben F. Koop
Summary: The coho salmon populations in North America have significantly declined, and analysis of genomic data suggests bottleneck events after glacial retreat as a possible cause. A chromosome-level genome assembly and genome resequencing of 83 coho salmon were performed to aid in stock management and conservation efforts.
G3-GENES GENOMES GENETICS
(2023)
Article
Oncology
Erica S. S. Tsang, Veronika Csizmok, Laura M. M. Williamson, Erin Pleasance, James T. T. Topham, Joanna M. M. Karasinska, Emma Titmuss, Intan Schrader, Stephen Yip, Basile Tessier-Cloutier, Karen Mungall, Tony Ng, Sophie Sun, Howard J. J. Lim, Jonathan M. M. Loree, Janessa Laskin, Marco A. A. Marra, Steven J. M. Jones, David F. F. Schaeffer, Daniel J. J. Renouf
Summary: Emerging evidence suggests a predictive role of homologous recombination deficiency (HRD) in gastrointestinal and thoracic malignancies. In this study, whole genome and transcriptomic data were reviewed to evaluate HRD scores and single base substitution 3 (SBS3) in advanced GI and thoracic cancers. The association between HRD and time to progression on platinum (TTPp) was examined, and it was found that SBS3 was more strongly associated with TTPp in GI malignancies. Tumors with gBRCA1/2 mutations and a somatic second alteration showed high SBS3 and HRD scores, indicating potential therapeutic targets.
NPJ PRECISION ONCOLOGY
(2023)
Article
Oncology
Elie J. Ritch, Cameron Herberts, Evan W. Warner, Sarah W. S. Ng, Edmond M. Kwan, Jack V. W. Bacon, Cecily Q. Bernales, Elena Schonlau, Nicolette M. Fonseca, Veda N. Giri, Corinne Maurice-Dror, Gillian Vandekerkhove, Steven J. M. Jones, Kim N. N. Chi, Alexander W. Wyatt
Summary: Specific classes of DNA damage repair defects can increase sensitivity to emerging therapies for metastatic prostate cancer. However, biomarker approaches based on DDR gene sequencing are not accurate predictors of DDR deficiency or treatment efficacy. We developed a machine learning approach using whole-exome sequencing data to simultaneously identify multiple types of DDR deficiencies in metastatic prostate cancer.
NPJ PRECISION ONCOLOGY
(2023)
Article
Genetics & Heredity
S. Yoo, E. Garg, L. T. Elliott, R. J. Hung, A. R. Halevy, J. D. Brooks, S. B. Bull, F. Gagnon, C. M. T. Greenwood, J. F. Lawless, A. D. Paterson, L. Sun, M. H. Zawati, J. Lerner-Ellis, R. J. S. Abraham, I Birol, G. Bourque, J-m Garant, C. Gosselin, J. Li, J. Whitney, B. Thiruvahindrapuram, J-a Herbrick, M. Lorenti, M. S. Reuter, O. O. Adeoye, S. Liu, U. Allen, F. P. Bernier, C. M. Biggs, A. M. Cheung, J. Cowan, M. Herridge, D. M. Maslove, B. P. Modi, V Mooser, S. K. Morris, M. Ostrowski, R. S. Parekh, G. Pfeffer, O. Suchowersky, J. Taher, J. Upton, R. L. Warren, R. S. M. Yeung, N. Aziz, S. E. Turvey, B. M. Knoppers, M. Lathrop, S. J. M. Jones, S. W. Scherer, L. J. Strug
Summary: HostSeq was launched in April 2020 to integrate whole genome sequencing data and clinical information of 10,000 Canadians infected with SARS-CoV-2. It aims to support research communities in understanding disease risk factors and developing interventions. HostSeq is a collaboration among 13 epidemiological studies across five provinces in Canada, providing aggregated data through two portals and individual-level data for global health research.
Article
Cell Biology
Vahid Akbari, Vincent C. T. Hanlon, Kieran O'Neill, Louis Lefebvre, Kasmintan A. Schrader, Peter M. Lansdorp, Steven J. M. Jones
Summary: Researchers have developed a method to determine the parent of origin for all human autosomes by integrating methylation-detecting nanopore sequencing with Strand-seq data. This method has the potential to improve the diagnosis and management of genetic diseases.
