Article
Multidisciplinary Sciences
Anil K. Panigrahi, David M. Lonard, Bert W. O'Malley
Summary: This study demonstrates the interdependence of transcription between enhancers and target promoters. The results suggest that transcriptional concurrence and coordination throughout the genome are based on the transcriptional interdependence of enhancers and promoters. The study proposes a model where enhancers and promoters are entangled in the form of enhancer-promoter contact, reside in a proteinaceous bubble, and utilize shared transcriptional resources and regulatory inputs.
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
(2023)
Article
Biochemistry & Molecular Biology
Kirill Nikitich Kashkin, Elena Sergeevna Kotova, Irina Vasilievna Alekseenko, Svetlana Sergeevna Bulanenkova, Sergey Borisovich Akopov, Eugene Pavlovich Kopantzev, Lev Grigorievich Nikolaev, Igor Pavlovich Chernov, Dmitry Alexandrovich Didych
Summary: A library of active genome regulatory elements from MIA PaCa-2 pancreatic adenocarcinoma cells was constructed using ChIP-lentiMPRA. Highly expressed genes were found to be enriched in those associated with multiple distal regions, while genes associated with 1-2 distal regions or proximal regions were more often related to housekeeping functions.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2022)
Article
Cell Biology
Kota Hamamoto, Takashi Fukaya
Summary: This review comprehensively discusses the molecular mechanisms underlying enhancer-promoter interaction, including the roles of looping factors, higher-order genome topology, and dynamic clustering of transcription apparatus. The cooperative interplay between "looping" and "hub" is proposed to enable distal enhancers to specifically and dynamically modulate target gene expression over large distances.
CURRENT OPINION IN CELL BIOLOGY
(2022)
Article
Biology
Xueying C. Li, Timothy Fuqua, Maria Elize van Breugel, Justin Crocker
Summary: Rapid enhancer and slow promoter evolution have been demonstrated through comparative genomics. However, it is not clear how this information is encoded genetically and if this can be used to place evolution in a predictive context. Here, researchers investigated the evolutionary capacity of promoter variation in Drosophila melanogaster through an unbiased mutation library survey. They found that mutations in promoters had limited to no effect on spatial patterns of gene expression. Compared to developmental enhancers, promoters are more robust to mutations and have more access to mutations that can increase gene expression, suggesting that their low activity might be a result of natural selection.
PHILOSOPHICAL TRANSACTIONS OF THE ROYAL SOCIETY B-BIOLOGICAL SCIENCES
(2023)
Article
Multidisciplinary Sciences
Kevin B. Dsouza, Alexandra Maslova, Ediem Al-Jibury, Matthias Merkenschlager, Vijay K. Bhargava, Maxwell W. Libbrecht
Summary: This paper proposes a method that generates low-dimensional latent representations to summarize intra-chromosomal Hi-C contacts, addressing the challenge of understanding the relationship between the 1D genome and 3D conformation.
NATURE COMMUNICATIONS
(2022)
Article
Biology
Rocio Espada, Nikola Zarevski, Adele Drame-Maigne, Yannick Rondelez
Summary: We introduce SINGLe, an error correction method that reduces noise in nanopore reads of amplicons containing point variations. SINGLe takes advantage of the similarity between all reads in an amplicon library and a wild-type sequence to characterize the systematic sequencing error pattern. It then uses this information to adjust the confidence given to nucleotides that do not match the wild-type, improving consensus calling.
Article
Biochemistry & Molecular Biology
Annabelle Wurmser, Srinjan Basu
Summary: This article discusses the relationship between cis-regulatory elements and enhancers, emphasizing the need to shift from a static to a dynamic view of this relationship. Recent studies have revealed the impact of chromatin movement on transcription, highlighting the influence of condensate microenvironments on the chromatin binding kinetics of proteins.
FRONTIERS IN MOLECULAR BIOSCIENCES
(2022)
Article
Developmental Biology
Nikolay Postika, Paul Schedl, Pavel Georgiev, Olga Kyrchanova
Summary: The Abd-B gene is regulated by four regulatory domains, each responsible for directing its expression in different abdominal segments. Tissue-specific enhancers in the iab-5 domain were found to be required for the proper activation of Abd-B in both A5 and A6. These findings suggest that the iab-5 and iab-6 domains function in an additive manner in the development of the adult cuticle A5 and A6.
Article
Biochemistry & Molecular Biology
Juhyun Kim, Ann Dean
Summary: The activity and selectivity of transcriptional enhancers play a crucial role in determining gene expression patterns that lead a zygote to develop into a complex organism. Recent advancements in technology have provided valuable insights into enhancer-promoter interactions and overall nuclear genome organization.
CURRENT OPINION IN STRUCTURAL BIOLOGY
(2021)
Article
Biochemical Research Methods
Xiaoping Min, Congmin Ye, Xiangrong Liu, Xiangxiang Zeng
Summary: The paper introduces a method called EPI-DLMH for predicting EPIs using only DNA sequences. By utilizing a convolutional neural network and bidirectional gated recurrent unit network to learn local features and long-range dependencies, as well as incorporating attention mechanism and matching heuristic mechanism, the method shows superior performance in multiple cell lines compared to existing models.
BRIEFINGS IN BIOINFORMATICS
(2021)
Article
Multidisciplinary Sciences
Chun-Ping Yu, Chen-Hao Kuo, Chase W. Nelson, Chi-An Chen, Zhi Thong Soh, Jinn-Jy Lin, Ru-Xiu Hsiao, Chih-Yao Chang, Wen-Hsiung Li
Summary: By developing a computational pipeline for analyzing ChIP-seq data, this study discovered and characterized a large number of previously unknown TFBSs, providing insights into the biological and genomic features of TFBSs.
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
(2021)
Article
Genetics & Heredity
Alisha T. Massa, Michelle R. Mousel, Maria K. Herndon, David R. Herndon, Brenda M. Murdoch, Stephen N. White
Summary: This study conducted the first genome-wide survey of regulatory elements in sheep immune cells, particularly alveolar macrophages, to identify cis-regulatory DNA elements and chromatin domain boundaries controlling gene expression. The findings revealed a large number of reproducible regulatory elements with potential biological functions, exceeding standards set by FAANG and ENCODE. Active elements were predictive of gene expression in alveolar macrophages, while silencer elements were enriched for repressed developmental genes, demonstrating the importance of regulatory elements in gene control mechanisms.
FRONTIERS IN GENETICS
(2021)
Article
Cell Biology
Kathryn Monfils, Tahsin Stefan Barakat
Summary: Enhancers and promoters are transcriptional regulatory elements that interact to increase gene expression. The mechanism facilitating enhancer-promoter interactions remains unclear, but mutations causing errors in these interactions have been linked to cancer and disease. Multiple models have been proposed to describe how enhancers go the distance to interact with promoters, including loop formation models and more complex hypotheses involving 3D chromatin organization and phase separation.
EUROPEAN JOURNAL OF CELL BIOLOGY
(2021)
Article
Oncology
XinTao Gao, Jiaqian Liang, LiYang Wang, Zhaoyang Zhang, Penghui Yuan, Jiaxin Wang, Yanfei Gao, Fen Ma, Carla Calagua, Huihui Ye, Olga Voznesensky, Shaogang Wang, Tao Wang, Jihong Liu, Shaoyong Chen, Xiaming Liu
Summary: The study highlights the significance of pS81 in CRPC, with its nuclear localization correlated with AR transactivation. ChIP analysis and ChIP-Seq demonstrated the enrichment of pS81 on AR-activated promoters.
MOLECULAR ONCOLOGY
(2021)
Article
Oncology
Peng Huang, Mengxiang Xu, Haijun Han, Xinyi Zhao, Ming D. Li, Zhongli Yang
Summary: DNA methylation plays a crucial role in regulating gene expression in hepatocellular carcinoma (HCC). This study identified a large number of differentially methylated CpG sites in HCC and highlighted the activation of cell cycle-related pathways and repression of metabolic pathways.
FRONTIERS IN ONCOLOGY
(2021)
Article
Oncology
Karsten Kleo, Vladimir M. Jovanovic, Alexander Arndold, Annika Lehmann, Hedwig Lammert, Erika Berg, Hannah Harloff, Christoph Treese, Michael Hummel, Severin Daum
Summary: The aim of this study was to identify predictive biomarkers in pre-therapeutic tumor biopsies from AEG/AS patients. Although discriminating target genes could not be identified, the data suggests that molecular alterations are more prevalent in non-responding AEG/AS patients.
JOURNAL OF CANCER RESEARCH AND CLINICAL ONCOLOGY
(2023)
Article
Genetics & Heredity
Pablo Mier, Jean-Fred Fontaine, Marah Stoldt, Romain Libbrecht, Carlotta Martelli, Susanne Foitzik, Miguel A. Andrade-Navarro
Summary: The gene family of insect olfactory receptors (ORs) has expanded greatly over the course of evolution. By assembling and comparing the sequences of ORs from different insect species, researchers found that social insect families have highly conserved binding sites in their ORs, indicating their sensitivity to similar odorants. This novel approach provides a powerful tool for studying the functional evolution of large gene families.
Article
Oncology
Carlotta Keunecke, Hagen Kulbe, Felix Dreher, Eliane T. Taube, Radoslav Chekerov, David Horst, Michael Hummel, Thomas Kessler, Klaus Pietzner, Wanja Kassuhn, Florian Heitz, Mustafa Z. Muallem, Susan M. Lang, Ignace Vergote, Oliver Dorigo, Hedwig Lammert, Andreas du Bois, Tim Angelotti, Christina Fotopoulou, Jalid Sehouli, Elena I. Braicu
Summary: This study aimed to discover and validate a predictive panel for surgical outcome of residual tumor mass after first-line debulking surgery. The Nanostring method and immunohistochemistry testing were used to validate a set of predictive genes and predict the presence of miliary carcinomatosis patterns. The results showed that tissue-based biomarkers cannot reliably predict post-operative residual tumor.
GYNECOLOGIC ONCOLOGY
(2022)
Article
Multidisciplinary Sciences
Daniel Reichart, Eric L. Lindberg, Henrike Maatz, Antonio M. A. Miranda, Anissa Viveiros, Nikolay Shvetsov, Anna Gaertner, Emily R. Nadelmann, Michael Lee, Kazumasa Kanemaru, Jorge Ruiz-Orera, Viktoria Strohmenger, Daniel M. DeLaughter, Giannino Patone, Hao Zhang, Andrew Woehler, Christoph Lippert, Yuri Kim, Eleonora Adami, Joshua M. Gorham, Sam N. Barnett, Kemar Brown, Rachel J. Buchan, Rasheda A. Chowdhury, Chrystalla Constantinou, James Cranley, Leanne E. Felkin, Henrik Fox, Ahla Ghauri, Jan Gummert, Masatoshi Kanda, Ruoyan Li, Lukas Mach, Barbara McDonough, Sara Samari, Farnoush Shahriaran, Clarence Yapp, Caroline Stanasiuk, Pantazis Theotokis, Fabian J. Theis, Antoon van den Bogaerdt, Hiroko Wakimoto, James S. Ware, Catherine L. Worth, Paul J. R. Barton, Young-Ae Lee, Sarah A. Teichmann, Hendrik Milting, Michela Noseda, Gavin Y. Oudit, Matthias Heinig, Jonathan G. Seidman, Norbert Hubner, Christine E. Seidman
Article
Oncology
J. J. Staudacher, Alexander Arnold, A. A. Kuehl, M. Poetzsch, S. Daum, M. Winterfeld, E. Berg, M. Hummel, B. Rau, U. Stein, C. Treese
Summary: This study aimed to investigate the prognostic role of activin tumor protein expression in esophageal and gastric adenocarcinomas. The results showed that higher levels of activin subunits were associated with lower cancer stage and longer overall survival. Furthermore, tumors with higher activin subunit expression also had higher CD4(+) T-cell infiltration, and the longer overall survival effect was only observed in tumors with high CD4(+) T-cell infiltration.
Article
Biochemistry & Molecular Biology
Bob A. Hersbach, David S. Fischer, Giacomo Masserdotti, Deeksha, Karolina Mojzisova, Thomas Waltzhoeni, Diego Rodriguez-Terrones, Matthias Heinig, Fabian J. Theis, Magdalena Goetz, Stefan H. Stricker
Summary: Collide-seq, a single-cell protocol, has shed light on the basic principles of fate erasure and cell identity conflict resolution in direct reprogramming. It revealed the lack of a common mechanism for the loss of fibroblast-specific gene expression and showed that the abrupt transcriptional changes in converting cells occur when critical levels of reprogramming factors are reached. The study also demonstrated that reprogramming factors can disturb cell identity programs independent of their ability to bind their target genes.
MOLECULAR SYSTEMS BIOLOGY
(2022)
Article
Biotechnology & Applied Microbiology
Dae-Kyum Kim, Benjamin Weller, Chung-Wen Lin, Dayag Sheykhkarimli, Jennifer J. Knapp, Guillaume Dugied, Andreas Zanzoni, Carles Pons, Marie J. Tofaute, Sibusiso B. Maseko, Kerstin Spirohn, Florent Laval, Luke Lambourne, Nishka Kishore, Ashyad Rayhan, Mayra Sauer, Veronika Young, Hridi Halder, Nora Marin-de la Rosa, Oxana Pogoutse, Alexandra Strobel, Patrick Schwehn, Roujia Li, Simin T. Rothballer, Melina Altmann, Patricia Cassonnet, Atina G. Cote, Lena Elorduy Vergara, Isaiah Hazelwood, Betty B. Liu, Maria Nguyen, Ramakrishnan Pandiarajan, Bushra Dohai, Patricia A. Rodriguez Coloma, Juline Poirson, Paolo Giuliana, Luc Willems, Mikko Taipale, Yves Jacob, Tong Hao, David E. Hill, Christine Brun, Jean-Claude Twizere, Daniel Krappmann, Matthias Heinig, Claudia Falter, Patrick Aloy, Caroline Demeret, Marc Vidal, Michael A. Calderwood, Frederick P. Roth, Pascal Falter-Braun
Summary: A study mapping the contactome between SARS-CoV-2 and human host proteins uncovers an inhibitor of viral replication and connects it to COVID-19 severity and human genetic architecture, providing important insights for therapy design and drug development.
NATURE BIOTECHNOLOGY
(2022)
Article
Biochemistry & Molecular Biology
Toray S. Akcan, Sergey Vilov, Matthias Heinig
Summary: DNA and RNA-binding trans-acting factors play a crucial role in regulating promoter-proximal RNA polymerase II (Pol II) pausing, which is a rate-limiting step in gene expression. In this study, we developed a machine learning model that accurately predicts the extent of Pol II pausing based on genomic and transcriptomic data, and identified previously unknown regulators of pausing.
NUCLEIC ACIDS RESEARCH
(2023)
Article
Pathology
Claudia Vollbrecht, Inga Hoffmann, Annika Lehmann, Sabine Merkelbach-Bruse, Jana Fassunke, Svenja Wagener-Ryczek, Markus Ball, Lora Dimitrova, Arndt Hartmann, Robert Stohr, Ramona Erber, Wilko Weichert, Nicole Pfarr, Lisa Bohlmann, Andreas Jung, Wolfgang Dietmaier, Manfred Dietel, David Horst, Michael Hummel
Summary: Precision oncology based on specific molecular alterations requires accurate and reliable detection of therapeutic targets. To ensure reproducible diagnostic results across laboratories, ring trials are essential. This study describes the design and results of a ring trial for detecting PIK3CA hotspot mutations in breast cancer tissue and liquid biopsy. The results show that NGS-based tests are more suitable for PIK3CA mutation detection than Sanger sequencing, and specific assays should be used for liquid biopsy to avoid false-negative results.
Article
Multidisciplinary Sciences
Philipp Jurmeister, Stefanie Gloess, Renee Roller, Maximilian Leitheiser, Simone Schmid, Liliana H. Mochmann, Emma Paya Capilla, Rebecca Fritz, Carsten Dittmayer, Corinna Friedrich, Anne Thieme, Philipp Keyl, Armin Jarosch, Simon Schallenberg, Hendrik Blaker, Inga Hoffmann, Claudia Vollbrecht, Annika Lehmann, Michael Hummel, Daniel Heim, Mohamed Haji, Patrick Harter, Benjamin Englert, Stephan Frank, Jurgen Hench, Werner Paulus, Martin Hasselblatt, Wolfgang Hartmann, Hildegard Dohmen, Ursula Keber, Paul Jank, Carsten Denkert, Christine Stadelmann, Felix Bremmer, Annika Richter, Annika Wefers, Julika Ribbat-Idel, Sven Perner, Christian Idel, Lorenzo Chiariotti, Rosa Della Monica, Alfredo Marinelli, Ulrich Schuller, Michael Bockmayr, Jacklyn Liu, Valerie J. Lund, Martin Forster, Matt Lechner, Sara L. Lorenzo-Guerra, Mario Hermsen, Pascal D. Johann, Abbas Agaimy, Philipp Seegerer, Arend Koch, Frank Heppner, Stefan M. Pfister, David T. W. Jones, Martin Sill, Andreas von Deimling, Matija Snuderl, Klaus-Robert Muller, Erna Forgo, Brooke E. Howitt, Philipp Mertins, Frederick Klauschen, David Capper
Summary: The authors used machine learning to classify sinonasal undifferentiated carcinomas into molecular classes and showed that the current terminology of SNUCs may not accurately reflect their differentiation state. Their findings provide insights into improving the diagnostic classification of sinonasal tumors.
NATURE COMMUNICATIONS
(2022)
Article
Medicine, Research & Experimental
Ina Rohwedder, Lou Martha Wackerbarth, Kristina Heinig, Annamaria Ballweg, Johannes Altstaetter, Myriam Ripphahn, Claudia Nussbaum, Melanie Salvermoser, Susanne Bierschenk, Tobias Straub, Matthias Gunzer, Marc Schmidt-Supprian, Thomas Kolben, Christian Schulz, Averil Ma, Barbara Walzog, Matthias Heinig, Markus Sperandio
Summary: Newborns, especially premature infants, are prone to developing neonatal sepsis due to differences in immune system requirements during intrauterine and extrauterine life. Through transcriptomic analysis, we have identified the molecular mechanisms of neutrophil maturation and functional adaptation in fetal ontogeny. Our findings reveal constitutive activation of the noncanonical NF-KB pathway and upregulation of A20 in fetal neutrophils, leading to appropriate adaptation of neutrophil function during intrauterine fetal life but potentially hampering immune responses in prematurely born infants.
Article
Public, Environmental & Occupational Health
Daniel Maier, Joerg Janne Vehreschild, Barbara Uhl, Sandra Meyer, Karin Berger-Thuermel, Melanie Boerries, Rickmer Braren, Viktor Gruenwald, Boris Hadaschik, Stefan Palm, Susanne Singer, Martin Stuschke, David Juarez, Pierre Delpy, Mohamed Lambarki, Michael Hummel, Caecilia Engels, Stefanie Andreas, Nicola Goekbuget, Kristina Ihrig, Susen Burock, Dietmar Keune, Angelika Eggert, Ulrich Keilholz, Hagen Schulz, Daniel Buettner, Steffen Loeck, Mechthild Krause, Mirko Esins, Frank Ressing, Martin Schuler, Christian Brandts, Daniel P. Brucker, Gabriele Husmann, Thomas Oellerich, Patrick Metzger, Frederik Voigt, Anna L. Illert, Matthias Theobald, Thomas Kindler, Ursula Sudhof, Achim Reckmann, Felix Schwinghammer, Daniel Nasseh, Wilko Weichert, Michael von Bergwelt-Baildon, Michael Bitzer, Nisar Malek, Oeznur Oener, Klaus Schulze-Osthoff, Stefan Bartels, Joerg Haier, Raimund Ammann, Anja Franziska Schmidt, Bernd Guenther, Melanie Janning, Bernd Kasper, Sonja Loges, Stephan Stilgenbauer, Peter Kuhn, Eugen Tausch, Silvana Runow, Alexander Kerscher, Michael Neumann, Martin Breu, Martin Lablans, Hubert Serve
Summary: The Clinical Communication Platform of the German Cancer Consortium is a potential catalyst for translational cancer research, providing comprehensive patient groups and improving understanding of the clinical course of various malignancies. It serves as a decision-making tool for clinical trial design and contributes to the evaluation of scientific findings in real-world conditions.
EUROPEAN JOURNAL OF EPIDEMIOLOGY
(2023)
Article
Biochemical Research Methods
Sergey Vilov, Matthias Heinig
Summary: In this study, a convolutional neural network-based approach called DeepSom is presented for detecting somatic single nucleotide polymorphism and short insertion and deletion variants in tumor whole-genome sequencing samples without a matched normal. The performance of DeepSom is validated on five different cancer datasets and it is demonstrated to outperform previously proposed methods for tumor-only somatic variant calling on whole-genome sequencing samples.
Article
Biotechnology & Applied Microbiology
Shuang Li, Katharina T. Schmid, Dylan H. de Vries, Maryna Korshevniuk, Corinna Losert, Roy Oelen, Irene van Blokland, Hilde E. Groot, Morris A. Swertz, Pim van der Harst, Harm-Jan Westra, Monique G. P. van der Wijst, Matthias Heinig, Lude Franke
Summary: This study uses single-cell data to reconstruct personalized co-expression networks and identifies SNPs altering co-expression patterns. These co-eQTLs are replicated in a large bulk cohort and provide novel insights into disease-associated variants and regulatory networks.
Article
Multidisciplinary Sciences
Florin Ratajczak, Mitchell Joblin, Marcel Hildebrandt, Martin Ringsquandl, Pascal Falter-Braun, Matthias Heinig
Summary: Understanding phenotype-genotype relationships is a challenge in biology, and the authors use graph representation learning to identify human genes with core gene characteristics for complex diseases. The core-like genes exhibit similar properties to core genes and are attractive targets for drug development.
NATURE COMMUNICATIONS
(2023)