Article
Biochemical Research Methods
Alberto Zenere, Olof Rundquist, Mika Gustafsson, Claudio Altafini
Summary: This article explores novel aspects of using paired RNA-seq and ATAC-seq data to investigate causal relationships between transcription factors, chromatin, and target genes. Results show a strong connection between selected regulatory motifs and structural balance in sample correlation graphs, suggesting that internal consistency is a necessary condition for satisfying causality rules in 3-node regulatory motifs.
Article
Multidisciplinary Sciences
Parashar Dhapola, Johan Rodhe, Rasmus Olofzon, Thomas Bonald, Eva Erlandsson, Shamit Soneji, Goran Karlsson
Summary: Scarf is a modularly designed Python package that enables memory-efficient single-cell analysis and can run on low-cost devices. It provides efficient implementations for memory and computation and supports accurate reference-anchored mapping and subsampling of large single-cell datasets.
NATURE COMMUNICATIONS
(2022)
Article
Biotechnology & Applied Microbiology
Dongyuan Song, Qingyang Wang, Guanao Yan, Tianyang Liu, Tianyi Sun, Jingyi Jessica Li
Summary: We introduce a statistical simulator, scDesign3, that can generate realistic single-cell and spatial omics data by learning interpretable parameters from real data. It uses a unified probabilistic model to infer biologically meaningful parameters, assess the goodness-of-fit of inferred cell clusters, trajectories, and spatial locations, and generate in silico negative and positive controls for benchmarking computational tools. The challenge of simulating multiomic single-cell data is addressed by a probabilistic model.
NATURE BIOTECHNOLOGY
(2023)
Article
Biotechnology & Applied Microbiology
Aileen R. Ferraro, Abigail J. Ameri, Zefu Lu, Masayuki Kamei, Robert J. Schmitz, Zachary A. Lewis
Summary: Regulation of chromatin accessibility and transcription are coordinated processes. This study characterizes accessible chromatin regions in Neurospora crassa, revealing molecular features and histone modifications associated with accessibility and inaccessibility. H3K27 acetylation is the most predictive histone modification for open chromatin in N. crassa, while H3K36 methylation is a key marker of inaccessible chromatin.
Article
Multidisciplinary Sciences
Xiang Lin, Tian Tian, Zhi Wei, Hakon Hakonarson
Summary: Single-cell multimodal sequencing technologies provide an opportunity to analyze different types of data in the same cell simultaneously. However, combining multiple data sources for clustering analysis of single-cell multimodal data remains a challenge. In this study, a novel deep learning method called scMDC is developed, which explicitly models different data sources and learns latent features for clustering analysis. The experimental results show that scMDC outperforms existing methods on single-cell multimodal datasets and has linear scalability for analyzing large datasets.
NATURE COMMUNICATIONS
(2022)
Article
Biochemistry & Molecular Biology
Zhilong Zhang, Yongfeng Zhang, Qi Bao, Yarong Gu, Chunnian Liang, Min Chu, Xian Guo, Pengjia Bao, Ping Yan
Summary: This study investigated the dynamic changes in chromatin accessibility during yak adipocyte differentiation using ATAC-seq. The results revealed the unique characteristics of open chromatin and identified the involvement of key pathways and transcription factors in regulating adipogenesis. This study provides valuable insights into the transcriptional regulatory mechanisms of adipogenesis and the adaptation of plateau species to high-altitude environments through fat metabolism.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2022)
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
Genetics & Heredity
Peter Y. Y. Guan, Jin Seok Lee, Lihao Wang, Kevin Z. Z. Lin, Wenwen Mei, Li Chen, Yuchao Jiang
Summary: We propose Destin2, a novel statistical and computational method for cross-modality dimension reduction, clustering, and trajectory reconstruction for single-cell ATAC-seq data. The framework integrates cellular-level epigenomic profiles from peak accessibility, motif deviation score, and pseudo-gene activity and learns a shared manifold using the multimodal input, followed by clustering and/or trajectory inference. We apply Destin2 to real scATAC-seq datasets and carry out benchmarking studies against existing methods based on unimodal analyses.
FRONTIERS IN GENETICS
(2023)
Article
Polymer Science
Kuixia Xie, Jingrun Yang, Qianqian Yao, Yang Xu, Yonglin Peng, Xinhua Liu
Summary: This study investigated the dynamic changes of chromatin accessibility and the transcriptome in dermal fibroblasts (DFs) during keloid formation. The results showed extensive alterations in chromatin accessibility and transcriptome in keloid DFs compared to normal samples. In addition, the downregulation of BRCA1 in keloid DFs was found to be closely associated with changes in gene expression, which may contribute to the formation of keloids.
Article
Biotechnology & Applied Microbiology
Guan-Dong Shang, Zhou-Geng Xu, Mu-Chun Wan, Fu-Xiang Wang, Jia-Wei Wang
Summary: In this study, we introduce FindIT2, a software package that can process and analyze multi-omics data to infer influential transcription factors using ChIP-seq/ATAC-seq datasets. The package annotates ChIP-seq/ATAC-seq peaks, identifies transcription factor targets by combining ChIP-seq and RNA-seq data, and supports inference of influential transcription factors based on different types of data input. Moreover, FindIT2 is compatible with any species with genomic annotations, making it particularly useful for less well-studied non-model species.
Article
Biotechnology & Applied Microbiology
Jeremie Breda, Mihaela Zavolan, Erik van Nimwegen
Summary: A Bayesian normalization procedure called Sanity is introduced in this study to address challenges in single-cell RNA-seq data normalization. The method outperforms other normalization methods in downstream tasks and effectively corrects for sampling noise and expression variability in the data.
NATURE BIOTECHNOLOGY
(2021)
Article
Genetics & Heredity
Shaopeng Liu, Daofeng Li, Cheng Lyu, Paul M. M. Gontarz, Benpeng Miao, Pamela A. F. Madden, Ting Wang, Bo Zhang
Summary: ATAC-seq is a widely used technique for investigating genome-wide chromatin accessibility, with the newly published Omni-ATAC-seq protocol improving signal/noise ratio and reducing input cell number. The AIAP analysis system enhances sensitivity in peak calling and differential analysis by providing a complete QC report and tools for ATAC-seq data.
GENOMICS PROTEOMICS & BIOINFORMATICS
(2021)
Article
Multidisciplinary Sciences
Lihua Zhang, Jing Zhang, Qing Nie
Summary: The emergence of single-cell multiomics data provides unprecedented opportunities to study the transcriptional regulatory mechanisms controlling cell identity. DIRECT-NET, a machine-learning method based on gradient boosting, allows us to identify genome-wide cis-regulatory elements (CREs) and their relationship to target genes from single-cell data. DIRECT-NET substantially improves the accuracy of inferring CRE-to-gene relationships and reveals cell subpopulation-specific and dynamic regulatory linkages.
Article
Biotechnology & Applied Microbiology
Hansen Cheng, Wenhao Ma, Kun Wang, Han Chu, Guangchao Bao, Yu Liao, Yawen Yuan, Yixiong Gou, Liting Dong, Jian Yang, Haoyang Cai
Summary: This study introduces an algorithm called ATACAmp that uses ATAC-seq data to detect ecDNA/HSRs in tumor genomes. The algorithm achieves high accuracy by enriching ecDNA and reducing chromosomal DNA interference. The method outperforms other tools in terms of accuracy and also supports single-cell analysis.
Article
Biotechnology & Applied Microbiology
Trevor F. Freeman, Qiuxia Zhao, Agustian Surya, Reed Rothe, Elif Sarinay Cenik
Summary: This study investigates the impact of depleting the ribosome biogenesis components RPOA-2 and GRWD-1 on chromatin accessibility using ATAC-seq. The results show similar changes in chromatin accessibility for both perturbations, but a weak correlation with gene expression.
Review
Transplantation
Wen Wen, Ignacio Portales-Castillo, Rituvanthikaa Seethapathy, Scott Krinsky, Daniela Kroshinsky, Sahir Kalim, Jeremy Goverman, Rosalynn M. Nazarian, Vipul Chitalia, Rajeev Malhotra, Rafael Kramann, Cindy K. Malhotra, Sagar U. Nigwekar
Summary: This study evaluated the effects and safety of intravenous sodium thiosulphate (STS) for vascular calcification (VC) in patients with chronic kidney disease (CKD). The results showed that STS treatment could attenuate the progression of VC and arterial stiffness, with no significant adverse effects observed.
NEPHROLOGY DIALYSIS TRANSPLANTATION
(2023)
Article
Oncology
Jennifer Eymael, Martijn van den Broek, Laura Miesen, Valerie Villacorta Monge, Bartholomeus T. van den Berge, Fieke Mooren, Vicky Luna Velez, Jelmer Dijkstra, Meyke Hermsen, Peter Bandi, Michiel Vermeulen, Saskia de Wildt, Brigith Willemsen, Sandrine Florquin, Roy Wetzels, Eric Steenbergen, Rafael Kramann, Marcus Moeller, Michiel F. Schreuder, Jack Fm Wetzels, Johan van der Vlag, Jitske Jansen, Bart Smeets
Summary: Scattered tubular cells (STCs) in the proximal tubule increase in number after acute kidney injury. STCs are preferentially located within the inner bends of the tubule and their number increases with age. STCs represent a transient state of dedifferentiated proximal tubule epithelial cells (PTECs) showing metabolic shift towards glycolysis, facilitating cellular survival after kidney injury.
JOURNAL OF PATHOLOGY
(2023)
Article
Multidisciplinary Sciences
David L. Hoelscher, Nassim Bouteldja, Mehdi Joodaki, Maria L. Russo, Yu-Chia Lan, Alireza Vafaei Sadr, Mingbo Cheng, Vladimir Tesar, Saskia V. Stillfried, Barbara M. Klinkhammer, Jonathan Barratt, Juergen Floege, Ian S. D. Roberts, Rosanna Coppo, Ivan G. Costa, Roman D. Buelow, Peter Boor
Summary: Pathology diagnostics still rely on tissue morphology assessment by trained experts. Here, the authors perform deep-learning-based segmentation followed by large-scale feature extraction of histological images, i.e., next-generation morphometry, to enable outcome-relevant and disease-specific pathomics analysis of non-tumor kidney pathology.
NATURE COMMUNICATIONS
(2023)
Article
Biochemical Research Methods
Zhijian Li, Chao-Chung Kuo, Fabio Ticconi, Mina Shaigan, Julia Gehrmann, Eduardo Gade Gusmao, Manuel Allhoff, Martin Manolov, Martin Zenke, Ivan G. Costa
Summary: This article introduces the Regulatory Genomics Toolbox (RGT), a computational library for the integrative analysis of regulatory genomics data. RGT provides different functionalities to handle genomic signals and regions, and several tools have been developed for distinct downstream analyses. RGT facilitates the customization of computational methods to analyze specific regulatory genomics problems.
BMC BIOINFORMATICS
(2023)
Article
Immunology
Mihael Vucur, Ahmed Ghallab, Anne T. Schneider, Arlind Adili, Mingbo Cheng, Mirco Castoldi, Michael T. Singer, Veronika Buettner, Leonie S. Keysberg, Lena Kuesgens, Marlene Kohlhepp, Boris Goerg, Suchira Gallage, Jose Efren Barragan Avila, Kristian Unger, Claus Kordes, Anne-Laure Leblond, Wiebke Albrecht, Sven H. Loosen, Carolin Lohr, Markus S. Joerdens, Anne Babler, Sikander Hayat, David Schumacher, Maria T. Koenen, Olivier Govaere, Mark Boekschoten, Simone Joers, Carlos Villacorta-Martin, Vincenzo Mazzaferro, Josep M. Llovet, Ralf Weiskirchen, Jakob N. Kather, Patrick Starlinger, Michael Trauner, Mark Luedde, Lara R. Heij, Ulf P. Neumann, Verena Keitel, Johannes G. Bode, Rebekka K. Shneider, Frank Tacke, Bodo Levkau, Twan Lammers, Georg Fluegen, Theodore Alexandrov, Amy L. Collins, Glyn Nelson, Fiona Oakley, Derek A. Mann, Christoph Roderburg, Thomas Longerich, Achim Weber, Augusto Villanueva, Andre L. Samson, James M. Murphy, Rafael Kramann, Fabian Geisler, Ivan G. Costa, Jan G. Hengstle, Mathias Heikenwalder, Tom Luedde
Summary: A molecular switch in hepatocytes can reprogram between two forms of necroptosis signaling, which fundamentally impacts immune responses and hepatocarcinogenesis.
Correction
Multidisciplinary Sciences
Julian Petersen, Lukas Englmaier, Artem V. Artemov, Irina Poverennaya, Ruba Mahmoud, Thibault Bouderlique, Marketa Tesarova, Ruslan Deviatiiarov, Anett Szilvasy-Szabo, Evgeny E. Akkuratov, David Pajuelo Reguera, Hugo Zeberg, Marketa Kaucka, Maria Eleni Kastriti, Jan Krivanek, Tomasz Radaszkiewicz, Kristina Gomoryova, Sarah Knauth, David Potesil, Zbynek Zdrahal, Ranjani Sri Ganji, Anna Grabowski, Miriam E. Buhl, Tomas Zikmund, Michaela Kavkova, Hakan Axelson, David Lindgren, Rafael Kramann, Christoph Kuppe, Ferenc Erdelyi, Zoltan Mate, Gabor Szabo, Till Koehne, Tibor Harkany, Kaj Fried, Jozef Kaiser, Peter Boor, Csaba Fekete, Jan Rozman, Petr Kasparek, Jan Prochazka, Radislav Sedlacek, Vitezslav Bryja, Oleg Gusev, Igor Adameyko
NATURE COMMUNICATIONS
(2023)
Article
Nutrition & Dietetics
Xoana Barros, Xenia Friesen, Vincent Mathias Brandenburg, Elisa Anamaria Liehn, Sonja Steppan, Fabian Kiessling, Rafael Kramann, Juergen Floege, Thilo Krueger, Nadine Kaesler
Summary: Cardiovascular complications are a major cause of death in patients with chronic kidney disease (CKD). Magnesium deficiency is common in CKD. A study on Wistar rats with CKD found that oral magnesium carbonate supplementation restored impaired left ventricular cardiac function and improved aortic wall integrity. This study provides evidence for the beneficial effect of magnesium on cardiovascular function in CKD.
Article
Engineering, Biomedical
Jose L. Gerardo-Nava, Jitske Jansen, Daniel Guenther, Laura Klasen, Anja Lena Thiebes, Bastian Niessing, Cedric Bergerbit, Anna A. Meyer, John Linkhorst, Mareike Barth, Payam Akhyari, Julia Stingl, Saskia Nagel, Thomas Stiehl, Angelika Lampert, Rudolf Leube, Matthias Wessling, Francesca Santoro, Sven Ingebrandt, Stefan Jockenhoevel, Andreas Herrmann, Horst Fischer, Wolfgang Wagner, Robert H. Schmitt, Fabian Kiessling, Rafael Kramann, Laura De Laporte
Summary: Recreating human tissues and organs in the petri dish to establish models as tools in biomedical sciences has gained momentum. Transformative materials play an important role in this evolution, as they can be programmed to direct cell behavior and fate. This paper illustrates state-of-the-art developments in in vitro tissue engineering and the challenges related to the design, production, and translation of transformative materials, emphasizing the need for convergence of different technologies to generate functional human tissue models.
ADVANCED HEALTHCARE MATERIALS
(2023)
Article
Engineering, Biomedical
Prachi Desai, Anshuman Dasgupta, Alexandros Marios Sofias, Quim Pena, Robert Goestl, Ioana Slabu, Ulrich Schwaneberg, Thomas Stiehl, Wolfgang Wagner, Stefan Jockenhoevel, Julia Stingl, Rafael Kramann, Christian Trautwein, Tim H. Bruemmendorf, Fabian Kiessling, Andreas Herrmann, Twan Lammers
Summary: Drug delivery systems (DDS) control drug availability and activity to achieve a balance between therapeutic efficacy and side effects. They overcome biological barriers encountered by drug molecules and are explored for modulating host-material interfaces. This article provides an overview of barriers and interfaces encountered by DDS in different administration routes and highlights material engineering advances for improved disease treatment.
ADVANCED HEALTHCARE MATERIALS
(2023)
Article
Cell Biology
Konrad Hoeft, Gideon J. L. Schaefer, Hyojin Kim, David Schumacher, Tore Bleckwehl, Qingqing Long, Barbara Mara Klinkhammer, Fabian Peisker, Lars Koch, James Nagai, Maurice Halder, Susanne Ziegler, Elisa Liehn, Christoph Kuppe, Jennifer Kranz, Sylvia Menzel, Ivan Costa, Adam Wahida, Peter Boor, Rebekka K. Schneider, Sikander Hayat, Rafael Kramann
Summary: Fibrosis is the result of chronic organ injury, causing tissue damage and organ failure. Spp1 macrophages, marked by expression of Spp1, Fn1, and Arg1, expand after organ injury and drive fibrosis. The chemokine CXCL4 plays a crucial role in the differentiation of profibrotic Spp1 macrophages and its loss leads to reduced fibrosis in heart and kidney injury. Platelets contribute to the differentiation of profibrotic Spp1 macrophages through the release of CXCL4. Macrophages orchestrate fibroblast activation through Spp1, Fn1, and Sema3 signaling. Moreover, Spp1 macrophages are found to be expanded in human chronic kidney disease and heart failure.
Article
Biology
Huaming Xu, Zhijian Li, Chao-Chung Kuo, Katrin Goetz, Thomas Look, Marcelo A. S. de Toledo, Kristin Sere, Ivan G. Costa, Martin Zenke
Summary: Transcription factor IRF8 plays a crucial role in the development and function of dendritic cells (DC). This study reveals that IRF8 autoactivation is initiated by enhancers and further controlled by a long non-coding RNA (lncRNA) promoter element in a specific type of DC. This negative feedback loop of IRF8 regulates DC differentiation.
Review
Medicine, General & Internal
Wen Wen, Ignacio Portales-Castillo, Rituvanthikaa Seethapathy, Olivia Durant, Beza Mengesha, Scott Krinsky, Daniela Kroshinsky, Sahir Kalim, Jeremy Goverman, Rosalynn M. Nazarian, Vipul Chitalia, Rajeev Malhotra, Rafael Kramann, Cindy K. Malhotra, Sagar U. Nigwekar
Summary: This is a meta-analysis on the treatment of calciphylaxis. The study found that intravenous sodium thiosulphate (STS) was not associated with skin lesion improvement or survival benefit compared to non-STS treatment in patients with chronic kidney disease (CKD). Further investigations are needed to examine the efficacy and safety of therapies for patients with calciphylaxis.
Article
Radiology, Nuclear Medicine & Medical Imaging
Sebastian Billig, Marc Hein, Mare Mechelinck, David Schumacher, Anna B. Roehl, Dieter Fuchs, Rafael Kramann, Moritz Uhlig
Summary: This study investigated the changes in coronary physiology in rats using ultrasound techniques. Both pulsed-wave Doppler (PWD) and myocardial contrast echocardiography (MCE) were used to assess the parameters at rest and under pharmacologically induced stress.
EUROPEAN RADIOLOGY EXPERIMENTAL
(2023)
Article
Biochemical Research Methods
Veronica Miguel, Katharina Charlotte Reimer, Anna Katharina Galyga, Jitske Jansen, Julia Moellmann, Luisa Meyer, Rebekka K. Schneider, Rafael Kramann
Summary: Metabolic derangement plays a crucial role in kidney pathophysiology, and organoids have shown great promise as an in vitro tool for kidney research. In this study, we present a refined protocol for analyzing bioenergetics in single kidney organoids derived from human induced pluripotent stem cells (iPSCs) using Seahorse XF96. Our protocol includes generating self-organized three-dimensional kidney organoids and preparing them for Seahorse XF96 analysis, followed by stress tests to determine mitochondrial and glycolytic rates in the organoids.
Article
Medicine, Research & Experimental
Christina Alter, Anne-Sophie Henseler, Christoph Owenier, Julia Hesse, Zhaoping Ding, Tobias Lautwein, Jasmin Bahr, Sikander Hayat, Rafael Kramann, Eva Kostenis, Juergen Scheller, Juergen Schrader
Summary: Plasma IL-6 is elevated after myocardial infarction (MI) and is mainly produced by cardiac fibroblasts (CFs), which are regulated by adenosine. These findings have important implications for the treatment of post-MI inflammation.
JOURNAL OF CLINICAL INVESTIGATION
(2023)