Article
Cell Biology
Yingjie Guo, Chenxi Wu, Zhian Yuan, Yansu Wang, Zhen Liang, Yang Wang, Yi Zhang, Lei Xu
Summary: This article introduces a gene-based method to detect gene-gene interactions by adding additive constraints to the model, and experimental results show that this method outperforms previous experiments in detecting gene-gene interactions.
FRONTIERS IN CELL AND DEVELOPMENTAL BIOLOGY
(2021)
Article
Computer Science, Interdisciplinary Applications
Xinyue Wang, Xiaoqian Jiang, Jaideep Vaidya
Summary: The paper proposes two algorithms for generating synthetic SNPs that are indistinguishable from real SNPs. Through game theoretic analysis, it demonstrates the possibility of incentivizing honest behavior by the server. Extensive experiments show that the proposed method can ensure efficient and trustworthy outsourcing of logistic regression for GWAS.
JOURNAL OF BIOMEDICAL INFORMATICS
(2021)
Article
Biochemical Research Methods
Ziga Avsec, Vikram Agarwal, Daniel Visentin, Joseph R. Ledsam, Agnieszka Grabska-Barwinska, Kyle R. Taylor, Yannis Assael, John Jumper, Pushmeet Kohli, David R. Kelley
Summary: Enformer leverages a new deep learning architecture to improve gene expression prediction accuracy based on DNA sequences, integrating information from long-range interactions in the genome and accurately predicting the impact of genetic variants on gene expression. Additionally, Enformer has learned to predict enhancer-promoter interactions directly from DNA sequences.
Article
Clinical Neurology
Longfei Jia, Fangyu Li, Cuibai Wei, Min Zhu, Qiumin Qu, Wei Qin, Yi Tang, Luxi Shen, Yanjiang Wang, Lu Shen, Honglei Li, Dantao Peng, Lan Tan, Benyan Luo, Qihao Guo, Muni Tang, Yifeng Du, Jiewen Zhang, Junjian Zhang, Jihui Lyu, Ying Li, Aihong Zhou, Fen Wang, Changbiao Chu, Haiqing Song, Liyong Wu, Xiumei Zuo, Yue Han, Junhua Liang, Qi Wang, Hongmei Jin, Wei Wang, Yang Lu, Fang Li, Yuying Zhou, Wei Zhang, Zhengluan Liao, Qiongqiong Qiu, Yan Li, Chaojun Kong, Haishan Jiao, Jie Lu, Jianping Jia
Summary: This study validated predictive models based on genome-wide association studies for assessing the risk of Alzheimer's disease onset in a large Chinese population. These models effectively predicted Alzheimer's disease onset in individuals carrying risk variants, confirming the contribution of these identified variants to disease pathogenesis.
Article
Biochemical Research Methods
Philippe Weitz, Yinxi Wang, Kimmo Kartasalo, Lars Egevad, Johan Lindberg, Henrik Gronberg, Martin Eklund, Mattias Rantalainen
Summary: This study proposes a new approach to predict gene expression profiles based on the morphological features of tumors. By using convolutional neural networks, gene expression profiles were successfully predicted from hematoxylin and eosin-stained images, offering a cost-effective solution for large-scale research studies and molecular diagnostics.
Article
Biochemistry & Molecular Biology
Max Highsmith, Jianlin Cheng
Summary: 4DMax is a novel method that predicts dynamic chromosome conformation using time-series Hi-C data, effectively interpolating chromatin position, recovering higher order features, and predicting contact maps even at time points where Hi-C data is unavailable.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2021)
Article
Biochemical Research Methods
Inaki Amatria-Barral, Jorge Gonzalez-Dominguez, Juan Tourino
Summary: lncRNA plays a key role in biological processes, and the detection and evaluation of lncRNA-DNA triple helices have been relatively underdeveloped. This study presents PATO, an efficient tool for accurately predicting triple helices at the genome scale in a short time. Compared to existing tools, PATO achieves higher levels of prediction accuracy in a shorter time.
Article
Biochemistry & Molecular Biology
Peter Majek, Lukas Lueftinger, Stephan Beisken, Thomas Rattei, Arne Materna
Summary: Predicting antimicrobial resistance based on genomic information can improve patient outcomes. Machine learning has been successfully applied to translate genetic mechanisms into phenotypic AMR. The addition of new features significantly improved predictive performance of trained AMR models for certain pathogens.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2021)
Article
Biochemistry & Molecular Biology
Sungwoo Choi, Seung Han Son, Min Young Kim, Insung Na, Vladimir N. Uversky, Chul Geun Kim
Summary: Proteins play a crucial role in biological processes, and abnormal protein-protein interactions (PPIs) are associated with diseases such as cancer. Studying protein-peptide interactions (PpIs) is challenging due to their dynamic and transient nature. In this study, an improved molecular docking method (3SD) was developed to predict PpI poses, addressing issues like intrinsically disordered regions (IDRs) and artificial intelligence-predicted structures. The study provides an improved solution to studying PpIs through computational docking and has the potential to contribute to PPIs-targeted drug discovery.
INTERNATIONAL JOURNAL OF BIOLOGICAL MACROMOLECULES
(2023)
Article
Biochemistry & Molecular Biology
Chiara Gasbarri, Serena Rosignoli, Giacomo Janson, Dalila Boi, Alessandro Paiardini
Summary: Protein-peptide interactions are crucial for cell processes and functions, and in silico predictions offer an affordable alternative to experimental methods. This study presents a new algorithm, PepThreader, for predicting and analyzing PPIs and PpIs. It achieved an accuracy of 80% on a benchmark dataset and adds to the existing tools for identifying and characterizing PPIs and PpIs.
Article
Multidisciplinary Sciences
Ting Peng, Yingping Hou, Haowei Meng, Yong Cao, Xiaotian Wang, Lumeng Jia, Qing Chen, Yang Zheng, Yujie Sun, Hebing Chen, Tingting Li, Cheng Li
Summary: A nucleolus Hi-C (nHi-C) experimental technique was developed to enrich nucleolus-associated chromatin interactions and revealed specific heterochromatin interaction patterns within and around nucleoli in human cells. The research provides a global view of these interactions and demonstrates the important role of nucleoli in the organization of 3D genome architecture.
NATURE COMMUNICATIONS
(2023)
Article
Agricultural Engineering
Li Xu, Jiajia Li, Victor M. Gonzalez Ramos, Christina Lyra, Ad Wiebenga, Igor V. Grigoriev, Ronald P. de Vries, Miia R. Makela, Mao Peng
Summary: This study presents a comparative analysis of sugar transporters (STs) in four filamentous fungi, revealing their diversity at the genomic/transcriptomic level and showing complex regulation patterns. The findings provide valuable insights into the function of STs and their potential applications in metabolic engineering.
BIORESOURCE TECHNOLOGY
(2024)
Article
Biotechnology & Applied Microbiology
Ratul Chowdhury, Nazim Bouatta, Surojit Biswas, Christina Floristean, Anant Kharkare, Koushik Roye, Charlotte Rochereau, Gustaf Ahdritz, Joanna Zhang, George M. Church, Peter K. Sorger, Mohammed AlQuraishi
Summary: This article reports the development of an end-to-end differentiable recurrent geometric network (RGN) called RGN2 for predicting protein structure using the protein sequence. Compared to AlphaFold2 and RoseTTAFold, RGN2 performs better on orphan proteins and designed protein classes, while achieving a computational speedup of up to 10^6-fold. These findings demonstrate the practical and theoretical advantages of protein language models over multiple sequence alignments (MSAs) in protein structure prediction.
NATURE BIOTECHNOLOGY
(2022)
Article
Biochemistry & Molecular Biology
Pol Picon-Pages, Monica Bosch-Morato, Laia Subirana, Francisca Rubio-Moscardo, Biuse Guivernau, Hugo Fanlo-Ucar, Melisa Ece Zeylan, Simge Senyuz, Victor Herrera-Fernandez, Ruben Vicente, Jose M. Fernandez-Fernandez, Jordi Garcia-Ojalvo, Attila Gursoy, Ozlem Keskin, Baldomero Oliva, Francesc Posas, Eulalia de Nadal, Francisco J. Munoz
Summary: Alzheimer's disease is caused by misfolded amyloid beta-peptide (Aβ) forming beta-sheets, but there are currently no treatments available to prevent it. Through a genome-wide screen in Saccharomyces cerevisiae, we identified 81 mammalian orthologue genes that enhance Aβ(1-42) toxicity and 157 that provide protection. Further studies revealed that calcium regulation, protein translation, and mitochondrial activity were the main cellular functions affected by Aβ oligomers (oAβ). We focused on SURF4, a protein that regulates the store-operated calcium channel (SOCE), and found that it contributes to oAβ(1-42) neurotoxicity by decreasing SOCE activity.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2023)
Article
Multidisciplinary Sciences
Abbas Saad Alatrany, Wasiq Khan, Abir Hussain, Dhiya Al-Jumeily
Summary: The increasing incidence of Alzheimer's disease (AD) poses socioeconomic challenges. In this study, a hybrid feature selection approach and neural network models are used to predict AD. The approach outperformed existing methods with 99% accuracy and f1-score, providing impactful outcomes for other chronic diseases.
Editorial Material
Multidisciplinary Sciences
Leonid A. Mirny
Summary: The study reveals that loop extrusion, essential for chromosome folding and function, also plays a crucial part in repairing double-strand DNA breaks.
Editorial Material
Cell Biology
Leonid A. Mirny, Irina Solovei
Summary: The paper discusses three types of chromatin loops and their distinct features and functions, highlighting the role of chromatin looping in genome organization and gene expression. The diversity in structure, maintenance, and function among different types of chromatin loops is emphasized.
NATURE REVIEWS MOLECULAR CELL BIOLOGY
(2021)
Article
Biochemistry & Molecular Biology
Bryan A. Ramirez-Corona, Stephanie Fruth, Oluchi Ofoegbu, Zeba Wunderlich
Summary: The study found that the mode of expression divergence varies between conditions within the Drosophila fat body. Trans-acting effects dominate in response to Gram-negative infection, while cis-acting effects dominate in Gram-positive and preinfection conditions. Before infection, compensatory effects in the fat body due to metabolic activity lead to changes in cis and trans that counteract each other.
Correction
Genetics & Heredity
Evgeny Z. Kvon, Rachel Waymack, Mario Gad, Zeba Wunderlich
NATURE REVIEWS GENETICS
(2021)
Article
Genetics & Heredity
Lily Li, Rachel Waymack, Mario Gad, Zeba Wunderlich
Summary: The study reveals that the expression of developmental genes is regulated by multiple enhancers and core promoters, which provide both redundancy and specificity. Specific burst properties during transcription, such as burst size and frequency, are most strongly tuned by the combination of promoters and enhancers. The presence of multiple promoters in a locus is due to enhancer preference and a need for redundancy, with broad promoters being common among developmental genes.
Article
Multidisciplinary Sciences
Rachel Waymack, Mario Gad, Zeba Wunderlich
Summary: Transgenic reporters are valuable tools for studying enhancers, but they may inhibit the expression of other genes. Competition for transcription factors is thought to be partially responsible for this inhibition of gene expression.
Article
Multidisciplinary Sciences
Bart J. H. Dequeker, Matthias J. Scherr, Hugo B. Brandao, Johanna Gassler, Sean Powell, Imre Gaspar, Ilya M. Flyamer, Aleksandar Lalic, Wen Tang, Roman Stocsits, Iain F. Davidson, Jan-Michael Peters, Karl E. Duderstadt, Leonid A. Mirny, Kikue Tachibana
Summary: This study reveals that the minichromosome maintenance (MCM) complex acts as a barrier in G1 phase for loop extrusion, reducing the number of CTCF-anchored loops and weakening TAD boundary insulation. The study also demonstrates that MCMs are physical barriers that frequently constrain cohesin translocation. The findings suggest that loop extrusion barriers, including MCMs, play a crucial role in shaping the three-dimensional genome.
Article
Multidisciplinary Sciences
Michele Gabriele, Hugo B. Brandao, Simon Grosse-Holz, Asmita Jha, Gina M. Dailey, Claudia Cattoglio, Tsung-Han S. Hsieh, Leonid Mirny, Christoph Zechner, Anders S. Hansen
Summary: This study reveals the rare and dynamic nature of chromatin looping in the Fbn2 TAD, with a looped fraction of approximately 3 to 6.5% and a median loop lifetime of approximately 10 to 30 minutes. The results suggest that functional interactions may be primarily regulated by single CTCF boundaries rather than the fully CTCF-CTCF looped state.
Article
Multidisciplinary Sciences
Sarah B. Reiff, Andrew J. Schroeder, Koray Kirli, Andrea Cosolo, Clara Bakker, Soohyun Lee, Alexander D. Veit, Alexander K. Balashov, Carl Vitzthum, William Ronchetti, Kent M. Pitman, Jeremy Johnson, Shannon R. Ehmsen, Peter Kerpedjiev, Nezar Abdennur, Maxim Imakaev, Serkan Utku Ozturk, Ugur Camoglu, Leonid A. Mirny, Nils Gehlenborg, Burak H. Alver, Peter J. Park
Summary: The 4D Nucleome (4DN) Network aims to study the complex structure and organization of chromosomes in the nucleus and their impact on disease biology. The 4DN Data Portal is a repository for datasets generated in the network, providing a primary resource for chromosome contact and nuclear architecture data.
NATURE COMMUNICATIONS
(2022)
Article
Biochemistry & Molecular Biology
Masahiro Nagano, Bo Hu, Shihori Yokobayashi, Akitoshi Yamamura, Fumiya Umemura, Mariel Coradin, Hiroshi Ohta, Yukihiro Yabuta, Yukiko Ishikura, Ikuhiro Okamoto, Hiroki Ikeda, Naofumi Kawahira, Yoshiaki Nosaka, Sakura Shimizu, Yoji Kojima, Ken Mizuta, Tomoko Kasahara, Yusuke Imoto, Killian Meehan, Roman Stocsits, Gordana Wutz, Yasuaki Hiraoka, Yasuhiro Murakawa, Takuya Yamamoto, Kikue Tachibana, Jan-Michel Peters, Leonid A. Mirny, Benjamin A. Garcia, Jacek Majewski, Mitinori Saitou
Summary: This study provides comprehensive insights into the nucleome analysis of mouse germ cell development in vitro, revealing the mechanisms of epigenetic reprogramming and euchromatization in spermatogonial development, and highlighting the importance of proper nucleome maturation for normal spermatogenesis.
Article
Multidisciplinary Sciences
Veer I. P. Keizer, Simon Grosse-Holz, Maxime Woringer, Laura Zambon, Koceila Aize, Maud Bongaerts, Fanny Delille, Lorena Kolar-Znika, Vittore F. Scolari, Sebastian Hoffmann, Edward J. Banigan, Leonid A. Mirny, Maxime Dahan, Daniele Fachinetti, Antoine Coulon
Summary: This study introduces a method to manipulate a genomic locus using controlled magnetic forces inside the nucleus of a living human cell. The results show that chromatin exhibits viscoelastic displacements in response to near-piconewton forces, challenging the view that interphase chromatin is a gel-like material.
Article
Multidisciplinary Sciences
Bryan A. Ramirez-Corona, Anna C. Love, Srikiran Chandrasekaran, Jennifer A. Prescher, Zeba Wunderlich
Summary: This article introduces a non-invasive bioluminescent imaging strategy that allows real-time observation of pathogen load changes in individual fruit flies. By using luminescent bacteria for monitoring, stochastic responses to infection can be studied over time in individuals, and the dynamics of microbial clearance can be visualized with high temporal resolution.
Article
Biochemistry & Molecular Biology
George Spracklin, Nezar Abdennur, Maxim Imakaev, Neil Chowdhury, Sriharsa Pradhan, Leonid A. A. Mirny, Job Dekker
Summary: In this study, the researchers profiled long-range contact frequencies in HCT116 colon cancer cells and identified three silent chromatin states. They found that heterochromatin marked by H3K9me3, HP1 alpha, and HP1 beta showed strong compartmentalization. Their findings also showed that disruption of DNA methyltransferase activity altered genome compartmentalization, leading to changes in chromatin state and chromosome organization.
NATURE STRUCTURAL & MOLECULAR BIOLOGY
(2023)
Article
Biochemical Research Methods
Alvaro Fletcher, Zeba Wunderlich, German Enciso
Summary: Enhancers are regulatory DNA sequences that bind transcription factors and control the expression of a target gene. Shadow enhancers are multiple enhancers that regulate the same target gene and are associated with most animal developmental genes. Studies show that shadow enhancers can provide more consistent transcription than single enhancers. However, it is still unknown why shadow enhancer TF binding sites are distributed across multiple enhancers instead of within a single large enhancer.
PLOS COMPUTATIONAL BIOLOGY
(2023)
Article
Biochemistry & Molecular Biology
Leonid A. Mirny
Summary: Structural biology traditionally focuses on the structures of proteins, nucleic acids, molecules and complexes. However, it is now widely recognized that the 3D organization of chromosomes should also be included, despite differences in scale and complexity. There are similarities between protein folding and chromosome folding processes, including affinity-mediated interactions and active processes. By analyzing these systems simultaneously, universal principles of biomolecular organization can be uncovered.
CURRENT OPINION IN STRUCTURAL BIOLOGY
(2023)