Article
Computer Science, Artificial Intelligence
Shushan Toneyan, Ziqi Tang, Peter K. Koo
Summary: This study introduces a unified evaluation framework and uses it to compare different binary and quantitative models for predicting chromatin accessibility data. The results show that quantitative modeling improves the generalizability and interpretability of the models, and a robustness metric is introduced to enhance model selection and variant effect predictions.
NATURE MACHINE INTELLIGENCE
(2022)
Editorial Material
Biochemistry & Molecular Biology
Nour J. Abdulhay, Vijay Ramani
Summary: The two recent papers investigate the cooperativity of transcription factors at cis-regulatory elements, showing that factor co-occupancy is commonly found in vivo and conserved across different organisms from flies to mice.
Review
Biochemistry & Molecular Biology
Arina O. Degtyareva, Elena Antontseva, Tatiana Merkulova
Summary: Many genetic variants affecting gene expression are found in the noncoding part of the genome, mainly through alterations in transcription factor binding. Advanced methods such as eQTL analysis and searching for allele-specific events in various sequencing data are used to identify regulatory variants and understand their functionality.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2021)
Article
Genetics & Heredity
Sofia Battaglia, Kevin Dong, Jingyi Wu, Zeyu Chen, Fadi J. Najm, Yuanyuan Zhang, Molly M. Moore, Vivian Hecht, Noam Shoresh, Bradley E. Bernstein
Summary: The use of targeted nanopore sequencing allowed researchers to analyze chromatin accessibility and DNA methylation on contiguous DNA molecules, leading to the identification of gene regulatory elements such as promoters, enhancers, insulators, and transcription factor binding sites. They also inferred relationships among dynamic elements within immune loci and determined the order of remodeling events during T cell stimulation. Additionally, they phased primary sequences and regulatory elements across the H19/IGF2 locus, revealing primate-specific features and a mechanism that overrides IGF2 imprinting in human cells.
Article
Biochemistry & Molecular Biology
Fan Wang, Xuefeng Bai, Yuezhu Wang, Yong Jiang, Bo Ai, Yong Zhang, Yuejuan Liu, Mingcong Xu, Qiuyu Wang, Xiaole Han, Qi Pan, Yanyu Li, Xuecang Li, Jian Zhang, Jun Zhao, Guorui Zhang, Chenchen Feng, Jiang Zhu, Chunquan Li
Summary: Accessible chromatin is a valuable feature for identifying regulatory elements and understanding transcriptional activity. ATACdb is a comprehensive human chromatin accessibility database that aims to provide publicly available resources on human chromatin accessibility data, with detailed annotations and illustrations of potential roles in tissue/cell type-specific manner. ATACdb also offers quality assurance processes, TF footprint inferences, and various (epi)genetic annotations within chromatin accessibility regions.
NUCLEIC ACIDS RESEARCH
(2021)
Article
Medicine, General & Internal
Rui Chen, Jiewei Liu, Shiwu Li, Xiaoyan Li, Yongxia Huo, Yong-Gang Yao, Xiao Xiao, Ming Li, Xiong-Jian Luo
Summary: Through functional genomics study, we have systematically revealed the gene regulatory mechanisms of PD risk variants, generated the landscape of potential PD causal variants, and identified promising candidate genes for further functional characterization and drug development.
Article
Biology
Diana Avalos, Guillaume Rey, Diogo M. Ribeiro, Anna Ramisch, Emmanouil T. Dermitzakis, Olivier Delaneau
Summary: An analysis of cis-regulatory domains (CRDs) derived from ChIP-seq peaks and methylation data reveals cell-type specific regulatory mechanisms in immunity. Important biological mechanisms, such as cell-specific transcription factor binding sites and immune disease-associated loci, are discovered through this study. CRD-QTLs aid in interpreting GWAS findings and mapping functional regulatory units using population genomics allows the discovery of important mechanisms in gene expression regulation in immune cells. This study establishes a comprehensive resource for understanding cell-type specific regulatory mechanisms of immunity.
COMMUNICATIONS BIOLOGY
(2023)
Article
Biochemistry & Molecular Biology
Xiusheng Zhu, Qitong Huang, Lei Huang, Jing Luo, Qing Li, Dashuai Kong, Biao Deng, Yi Gu, Xueyan Wang, Chenying Li, Siyuan Kong, Yubo Zhang
Summary: Proper cell fate determination relies on precise spatial and temporal genome-wide cooperation between regulatory elements and their targeted genes. A method called MAE-seq was developed to experimentally identify functional regulatory elements at a 25-bp scale. Using this method, a large number of 25-bp enhancers were identified in mouse embryonic stem cells, C2C12, and HEK 293T. These 25-bp sequences were shown to act as functional units and contribute to gene regulation and genomic landscape exploration.
NUCLEIC ACIDS RESEARCH
(2023)
Article
Biochemistry & Molecular Biology
Deborah Weighill, Marouen Ben Guebila, Kimberly Glass, John Quackenbush, John Platig
Summary: Understanding how individual genotypes influence gene regulation can improve our understanding of human health and development. EGRET is a method that infers genotype-specific gene regulatory networks to reveal the genetic associations driving complex phenotypes.
Article
Immunology
Si-Yu Yang, Jie Long, Meng-Xing Huang, Pan-Yue Luo, Zhen-Hua Bian, Ya-Fei Xu, Cheng-Bo Wang, Shu-Han Yang, Liang Li, Carlo Selmi, M. Eric Gershwin, Zhi-Bin Zhao, Zhe-Xiong Lian
Summary: Regulatory B cells (Breg) are immunosuppressive cells with different subsets identified in various organs. This study used high-throughput single-cell RNA sequencing and B-cell receptor sequencing to define the phenotype of Breg cells. The research revealed organ-specific subsets of Breg cells, with non-B10 Breg cells exhibiting unique immunosuppressive properties linked to TGF-beta pathway activation.
FRONTIERS IN IMMUNOLOGY
(2021)
Article
Biochemistry & Molecular Biology
Xueqing Wang, Quanlong Jiang, Yuanyuan Song, Zhidong He, Hongdao Zhang, Mengjiao Song, Xiaona Zhang, Yumin Dai, Oezlem Karalay, Christoph Dieterich, Adam Antebi, Ligang Wu, Jing-Dong J. Han, Yidong Shen
Summary: Ageing is a complex process with different features in different tissues. This study isolated cells from different tissues in worms and analyzed the transcriptomic changes during ageing, revealing the diversity of ageing across tissues and identifying tissue-specific longevity regulators. Additionally, novel factors controlling intestinal barrier integrity and sarcomere structure during ageing were discovered.
Article
Physiology
Kesong Shi, Baoluri Wang, Le Dou, Shu Wang, Xinrui Fu, Haiquan Yu
Summary: Through the analysis of multiple datasets, we identified SSC-specific transcription factors and core genes, and revealed the complex regulatory network of these factors and genes in the process of SSC formation. These findings are of great significance for improving the induction efficiency of ESC differentiation into SSCs in vitro.
FRONTIERS IN PHYSIOLOGY
(2022)
Editorial Material
Genetics & Heredity
Emily R. Miraldi, Xiaoting Chen, Matthew T. Weirauch
Summary: A new study introduces a novel deep-learning approach to decode the syntax of transcription-factor binding from high-resolution ChIP-nexus data. In silico simulations confirmed complex sequence-based predictions, including helical periodicity and directional cooperativity between transcription factors.
Article
Biochemistry & Molecular Biology
Ming-an Sun, Gernot Wolf, Yejun Wang, Anna D. Senft, Sherry Ralls, Jinpu Jin, Caitlin E. Dunn-Fletcher, Louis J. Muglia, Todd S. Macfarlan
Summary: The study identified numerous lineage-specific gene expression in different mammalian placentae, shedding light on the evolutionary process of placenta. The overlap between specific families of endogenous retroviruses and lineage-specific placental enhancers likely facilitates the lineage-specific evolution of the mammalian placenta.
MOLECULAR BIOLOGY AND EVOLUTION
(2021)
Article
Biochemical Research Methods
Dania Machlab, Lukas Burger, Charlotte Soneson, Filippo M. Rijli, Dirk Schuebeler, Michael B. Stadler
Summary: Proteins binding to specific nucleotide sequences, such as transcription factors, have significant roles in regulating gene expression. The monaLisa package, an R/Bioconductor package, provides methods to identify relevant transcription factors from experimental data. It allows seamless motif analyses without relying on software outside of R.
Article
Genetics & Heredity
Eduardo Calpena, Maud Wurmser, Simon J. McGowan, Rodrigo Atique, Debora R. Bertola, Michael L. Cunningham, Jonas A. Gustafson, David Johnson, Jenny E. Morton, Maria Rita Passos-Bueno, Andrew T. Timberlake, Richard P. Lifton, Steven A. Wall, Stephen R. F. Twigg, Pascal Maire, Andrew O. M. Wilkie
Summary: This study identified an association between craniosynostosis and heterozygous SIX1 gene variants, particularly loss-of-function variants. Screening for SIX1 is recommended in craniosynostosis, especially when specific symptoms are present.
JOURNAL OF MEDICAL GENETICS
(2022)
Article
Genetics & Heredity
Eduardo Calpena, Simon J. McGowan, Fiona Blanco Kelly, Elise Boudry-Labis, Anne Dieux-Coeslier, Rachel Harrison, Diana Johnson, Katherine Lachlan, Jenny E. V. Morton, Helen Stewart, Pradeep Vasudevan, Stephen R. F. Twigg, Andrew O. M. Wilkie
Summary: Heterozygous deletions near the ERF gene can lead to a range of intellectual disabilities, with smaller deletions associated with milder ID and larger deletions affecting more centromeric genes leading to moderate ID. The most severe intellectual disabilities were found in individuals with deletions extending further into the telomeric region, including the CIC gene. Children with ERF deletions should be evaluated for craniofacial issues to rule out intracranial pressure abnormalities.
Article
Biochemical Research Methods
Damien J. Downes, Alastair L. Smith, Magdalena A. Karpinska, Taras Velychko, Kevin Rue-Albrecht, David Sims, Thomas A. Milne, James O. J. Davies, A. Marieke Oudelaar, Jim R. Hughes
Summary: This article introduces the application of Capture-C method in DNA analysis. The method uses oligonucleotide probes to enrich DNA regions in close proximity in the nucleus and obtains results through experimental and computational analysis. The method is modular and has several variations that can be applied to different samples and research needs.
Review
Genetics & Heredity
Jennifer C. Herrmann, Robert A. Beagrie, Jim R. Hughes
Summary: This article reviews the current understanding of the role of enhancers and their interactions in cell type-specific gene expression, as well as the recent progress achieved with experimental methods of unprecedented resolution.
TRENDS IN GENETICS
(2022)
Article
Multidisciplinary Sciences
Dominic D. G. Owens, Giorgio Anselmi, A. Marieke Oudelaar, Damien J. Downes, Alessandro Cavallo, Joe R. Harman, Ron Schwessinger, Akin Bucakci, Lucas Greder, Sara de Ornellas, Danuta Jeziorska, Jelena Telenius, Jim R. Hughes, Marella F. T. R. de Bruijn
Summary: The transcription factor RUNX1 is a critical regulator of developmental hematopoiesis and is frequently disrupted in leukemia. The complex gene Runx1 has two alternative promoters and multiple hematopoietic enhancers. The study reveals that dynamic sub-TAD chromatin boundaries play a role in establishing TAD structure and coordinated gene expression in large multi-promoter developmental genes.
NATURE COMMUNICATIONS
(2022)
Article
Biochemistry & Molecular Biology
David J. Ahern, Zhichao Ai, Mark Ainsworth, Chris Allan, Alice Allcock, Brian Angus, M. Azim Ansari, Carolina Arancibia-Carcamo, Dominik Aschenbrenner, Moustafa Attar, J. Kenneth Baillie, Eleanor Barnes, Rachael Bashford-Rogers, Archana Bashyal, Sally Beer, Georgina Berridge, Amy Beveridge, Sagida Bibi, Tihana Bicanic, Luke Blackwell, Paul Bowness, Andrew Brent, Andrew Brown, John Broxholme, David Buck, Katie L. Burnham, Helen Byrne, Susana Camara, Ivan Candido Ferreira, Philip Charles, Wentao Chen, Yi-Ling Chen, Amanda Chong, Elizabeth A. Clutterbuck, Mark Coles, Christopher P. Conlon, Richard Cornall, Adam P. Cribbs, Fabiola Curion, Emma E. Davenport, Neil Davidson, Simon Davis, Calliope A. Dendrou, Julie Dequaire, Lea Dib, James Docker, Christina Dold, Tao Dong, Damien Downes, Hal Drakesmith, Susanna J. Dunachie, David A. Duncan, Chris Eijsbouts, Robert Esnouf, Alexis Espinosa, Rachel Etherington, Benjamin Fairfax, Rory Fairhead, Hai Fang, Shayan Fassih, Sally Felle, Maria Fernandez Mendoza, Ricardo Ferreira, Roman Fischer, Thomas Foord, Aden Forrow, John Frater, Anastasia Fries, Veronica Gallardo Sanchez, Lucy C. Garner, Clementine Geeves, Dominique Georgiou, Leila Godfrey, Tanya Golubchik, Maria Gomez Vazquez, Angie Green, Hong Harper, Heather A. Harrington, Raphael Heilig, Svenja Hester, Jennifer Hill, Charles Hinds, Clare Hird, Ling-Pei Ho, Renee Hoekzema, Benjamin Hollis, Jim Hughes, Paula Hutton, Matthew A. Jackson-Wood, Ashwin Jainarayanan, Anna James-Bott, Kathrin Jansen, Katie Jeffery, Elizabeth Jones, Luke Jostins, Georgina Kerr, David Kim, Paul Klenerman, Julian C. Knight, Vinod Kumar, Piyush Kumar Sharma, Prathiba Kurupati, Andrew Kwok, Angela Lee, Aline Linder, Teresa Lockett, Lorne Lonie, Maria Lopopolo, Martyna Lukoseviciute, Jian Luo, Spyridoula Marinou, Brian Marsden, Jose Martinez, Philippa C. Matthews, Michalina Mazurczyk, Simon McGowan, Stuart McKechnie, Adam Mead, Alexander J. Mentzer, Yuxin Mi, Claudia Monaco, Ruddy Montadon, Giorgio Napolitani, Isar Nassiri, Alex Novak, Darragh P. O'Brien, Daniel O'Connor, Denise O'Donnell, Graham Ogg, Lauren Overend, Inhye Park, Ian Pavord, Yanchun Peng, Frank Penkava, Mariana Pereira Pinho, Elena Perez, Andrew J. Pollard, Fiona Powrie, Bethan Psaila, T. Phuong Quan, Emmanouela Repapi, Santiago Revale, Laura Silva-Reyes, Jean-Baptiste Richard, Charlotte Rich-Griffin, Thomas Ritter, Christine S. Rollier, Matthew Rowland, Fabian Ruehle, Mariolina Salio, Stephen Nicholas Sansom, Raphael Sanches Peres, Alberto Santos Delgado, Tatjana Sauka-Spengler, Ron Schwessinger, Giuseppe Scozzafava, Gavin Screaton, Anna Seigal, Malcolm G. Semple, Martin Sergeant, Christina Simoglou Karali, David Sims, Donal Skelly, Hubert Slawinski, Alberto Sobrinodiaz, Nikolaos Sousos, Lizzie Stafford, Lisa Stockdale, Marie Strickland, Otto Sumray, Bo Sun, Chelsea Taylor, Stephen Taylor, Adan Taylor, Supat Thongjuea, Hannah Thraves, John A. Todd, Adriana Tomic, Orion Tong, Amy Trebes, Dominik Trzupek, Felicia Anna Tucci, Lance Turtle, Irina Udalova, Holm Uhlig, Erinke van Grinsven, Iolanda Vendrell, Marije Verheul, Alexandru Voda, Guanlin Wang, Lihui Wang, Dapeng Wang, Peter Watkinson, Robert Watson, Michael Weinberger, Justin Whalley, Lorna Witty, Katherine Wray, Luzheng Xue, Hing Yuen Yeung, Zixi Yin, Rebecca K. Young, Jonathan Youngs, Ping Zhang, Yasemin-Xiomara Zurke
Summary: The study presents a comprehensive blood atlas for patients with varying severity of COVID-19, compared to influenza, sepsis patients, and healthy volunteers. The results identify immune signatures and correlates of host response, including cells, inflammatory mediators, immune repertoire, and metabolic and coagulation features. The study also reveals that persistent immune activation is a specific feature of COVID-19. Plasma proteomic analysis enables sub-phenotyping and prediction of severity and outcome. Integrative analyses show feature groupings linked with severity and specificity compared to influenza and sepsis.
Article
Biochemical Research Methods
Lance D. Hentges, Martin J. Sergeant, Christopher B. Cole, Damien J. Downes, Jim R. Hughes, Stephen Taylor
Summary: This article introduces a peak calling framework based on deep learning, which improves the accuracy of peak calling by recognizing peak shapes and performing multifaceted enrichment calculations. In multiple genome sequencing experiments, the framework shows better selectivity and sensitivity compared to traditional methods.
Article
Multidisciplinary Sciences
Julia Truch, Damien J. Downes, Caroline Scott, E. Ravza Gur, Jelena M. Telenius, Emmanouela Repapi, Ron Schwessinger, Matthew Gosden, Jill M. Brown, Stephen Taylor, Pak Leng Cheong, Jim R. Hughes, Douglas R. Higgs, Richard J. Gibbons
Summary: The chromatin remodeling complex ATRX promotes gene expression by binding G-quadruplexes and interacts with histone chaperone DAXX to deposit histone variant H3.3. ATRX binds repetitive and heterochromatic regions of the genome, playing a role in various nuclear processes. Mutations in ATRX lead to perturbation of gene expression and chromatin accessibility, particularly in erythroid cells.
NATURE COMMUNICATIONS
(2022)
Article
Genetics & Heredity
Ioanna Pavlaki, Michael Shapiro, Giuseppina J. Pisignano, Stephanie M. E. R. Jones, Jelena W. Telenius, Silvia M. Munoz-Descalzo, Robert Williams, Jim M. Hughes, Keith Vance
Summary: Central nervous system-expressed long non-coding RNAs (lncRNAs) are often located near protein coding genes involved in transcriptional control. The study identified the cis-regulatory interactions controlling the co-expression of the Paupar-Pax6 lncRNA-mRNA locus in the brain. The TCF7L2 transcription factor binds to specific cis-regulatory elements to regulate the expression of Paupar and Pax6 together.
Article
Multidisciplinary Sciences
D. M. Jeziorska, E. A. J. Tunnacliffe, J. M. Brown, H. Ayyub, J. Sloane-Stanley, J. A. Sharpe, B. C. Lagerholm, C. Babbs, A. J. H. Smith, V. J. Buckle, D. R. Higgs
Summary: The authors observed transcription dynamics during erythropoiesis and found that the pattern of transcriptional bursting changes during differentiation. Variability in individual cells is significantly reduced at the peak period of gene expression.
NATURE COMMUNICATIONS
(2022)
Article
Biochemistry & Molecular Biology
Mira Kassouf, Seren Ford, Joseph Blayney, Doug Higgs
Summary: Despite the availability of genomic data, the mechanisms behind gene activation during development and differentiation are still not fully understood. This review focuses on enhancers, promoters, and insulators, and their roles in regulating gene expression. It explores how enhancers and promoters are activated during differentiation and how multiple enhancers collaborate to control gene expression. The review also highlights the perturbation of enhancers in enhanceropathies, using the α-globin gene cluster as a model.
Correction
Biochemical Research Methods
Damien J. Downes, Alastair L. Smith, Magdalena A. Karpinska, Taras Velychko, Kevin Rue-Albrecht, David Sims, Thomas A. Milne, James O. J. Davies, A. Marieke Oudelaar, Jim R. Hughes
Article
Hematology
Caroline Scott, Damien J. Downes, Jill M. Brown, Robert Beagrie, Aude-Anais Olijnik, Matthew Gosden, Ron Schwessinger, Christopher A. Fisher, Anna Rose, David J. P. Ferguson, Errin Johnson, Quentin A. Hill, Steven Okoli, Raffaele Renella, Kate Ryan, Marjorie Brand, Jim Hughes, Noemi B. A. Roy, Douglas R. Higgs, Christian Babbs, Veronica J. Buckle
Summary: The investigation of inherited disorders of erythropoiesis has shed light on the production of normal red blood cells and its disruption in human diseases. CDA-I, a rare form of anemia, is caused by mutations in CDAN1 and CDIN1 genes, with underlying pathways yet to be fully understood. Studies have shown that erythroid cells in CDA-I exhibit delayed terminal erythroid differentiation, increased proliferation, and widespread changes in chromatin accessibility.