Article
Biochemical Research Methods
Yuridia S. Posadas-Garcia, Carlos Espinosa-Soto
Summary: This study investigates how gene duplication affects the behavior of gene regulatory networks and finds that gene duplication often mitigates the impact of new mutations, and this effect is not merely due to changes in the number of genes.
BMC BIOINFORMATICS
(2022)
Article
Biology
Stefan Landmann, Caroline M. Holmes, Mikhail Tikhonov
Summary: Bacteria can learn the structure of environmental fluctuations through evolution, while also inferring and acting upon environmental statistics through physiological mechanisms. Research shows that a common regulatory motif is sufficient for bacteria to learn the statistical structure of the environment and translate this information into predictive behavior, accomplishing these tasks near-optimally.
Article
Multidisciplinary Sciences
Thanakorn Jaemthaworn, Saowalak Kalapanulak, Treenut Saithong
Summary: This study explores gene cooperation patterns in cassava cultivars by analyzing the topology of gene co-expression networks, finding that resistant cultivars have higher topological clustering of cooperative genes compared to susceptible cultivars. Despite a reduction in hub genes, essential biological functions in the network are maintained through neighboring genes in the resistant cultivar. The susceptible cultivar induces more gene actions in the network but fails to maintain necessary functions for plant growth, highlighting the significance of regulatory network architecture in ensuring phenotypic robustness.
SCIENTIFIC REPORTS
(2021)
Article
Computer Science, Theory & Methods
Satyaki Roy, Preetam Ghosh, Nirnay Ghosh, Sajal K. Das
Summary: The emergence of the edge computing network paradigm has improved network performance but faces optimization challenges related to the topological robustness of biological networks. The study of transcriptional regulatory networks as biological networks provides inspiration for the design of intelligent networking protocols and architectures.
ACM COMPUTING SURVEYS
(2021)
Article
Biochemical Research Methods
Vivek Kohar, Danya Gordin, Ataur Katebi, Herbert Levine, Jose N. Onuchic, Mingyang Lu
Summary: GeneEx is an interactive web-app that uses ODE-based mathematical modeling approach to simulate, visualize and analyze gene regulatory circuits. Users can modify simulation parameters and network topology for exploring various hypotheses. Additionally, users can upload experimental data for comparison and GeneEx provides a curated database for further research on circuit motifs and biological regulatory circuits.
Article
Engineering, Electrical & Electronic
Maurizio Ciampa
Summary: In this article, the problem of determining the state of a diode in a circuit without numerical computation is considered. A set of topological conditions is proposed such that when verified by the diode, its state is determined and consistent in all solutions of the circuit. This may simplify the usual trial-and-error procedure to find solutions.
IEEE TRANSACTIONS ON CIRCUITS AND SYSTEMS I-REGULAR PAPERS
(2021)
Article
Plant Sciences
Liping Shen, Feng Tian, Zhukuan Cheng, Qiang Zhao, Qi Feng, Yan Zhao, Bin Han, Yuhan Fang, Yanan Lin, Rui Chen, Donghui Wang, Wenfeng Sun, Jiaqi Sun, Hongyun Zeng, Nan Yao, Ge Gao, Jingchu Luo, Zhihong Xu, Shunong Bai
Summary: This study reveals the important role of OsMADS58 in stamen development in rice by analyzing a CRISPR knockout mutant. It suggests that OsMADS58 may exert pleiotropic effects on stamen development by stabilizing gene regulatory circuits during early stages.
Article
Statistics & Probability
Bingkai Wang, Ryoko Susukida, Ramin Mojtabai, Masoumeh Amin-Esmaeili, Michael Rosenblum
Summary: The article introduces model-robust estimators that combine stratified randomization and covariate adjustment, and demonstrates that these estimators can substantially improve precision and power in clinical trials.
JOURNAL OF THE AMERICAN STATISTICAL ASSOCIATION
(2023)
Article
Multidisciplinary Sciences
Ivan Rodrigo Wolf, Rafael Plana Simoes, Guilherme Targino Valente
Summary: The study reveals that K-nn, page rank, and degree are the most relevant topological features in GRNs, significantly influencing the control of life-essential subsystems. The importance of transcription factors in biological systems depends mainly on K-nn and page rank or degree. Gene/genome duplication is a crucial evolutionary process that enhances K-nn as the most relevant feature.
SCIENTIFIC REPORTS
(2021)
Article
Materials Science, Multidisciplinary
Yinong Zhou, Ruqian Wu
Summary: In this study, the possibility of direct control of topological corner states is demonstrated by introducing spin degrees of freedom and local magnetization and electric potential in a rhombus-shaped Kekule nanostructure. By applying local magnetization on one corner, strong spin polarization can be achieved in both corners. Reversal of spin polarization at both corners is achieved by applying local electric potential at the same corner. The robustness of spin polarization control under disorder is also proven, and material realization is demonstrated in a gamma-graphyne nanostructure. Other higher-order lattices and nanostructure shapes are discussed as well. These studies provide a showcase of the remote correlation of quantum states in higher-order topological materials for spintronic and quantum applications.
Article
Nanoscience & Nanotechnology
Yanxin Lu, Qishan Liu, Yihang Chen, Zefeng Chen, Dan-Wei Zhang, Hanying Deng, Shi-Liang Zhu, Peng Han, Nian-Hai Shen, Thomas Koschny, Costas M. Soukoulis
Summary: The effective mass in the Dirac equation model is utilized to describe the state of electrons and determine the topological character in condensed-matter systems. In this study, it is shown that the band-gap topological property of a photonic crystal can be related to a pseudo effective mass through mapping Maxwell's equations to a Dirac-like equation. Altering the sign of the pseudo effective mass through surface modification leads to a topological transition in the photonic crystal, confirmed by the emergence of a zero-dimensional topological bound state. This research offers a new approach for manipulating the topological properties of optical systems.
Article
Biology
Reemy Ali Nasser, Yuval Harel, Shay Stern
Summary: This study demonstrates that early-life starvation in C. elegans has behavioral effects that are exposed during early and late developmental stages and buffered during intermediate stages. Dopamine and serotonin play opposite roles in shaping behavioral responses at different developmental timepoints. Unsupervised analysis reveals multiple dimensions of individual biases and experience-dependent effects on these dimensions.
Review
Biochemistry & Molecular Biology
Seungsoo Kim, Joanna Wysocka
Summary: Uncovering the cis-regulatory code that governs gene transcription in a given genome and cellular state remains a central goal of biology. This review discusses the different layers of regulation that influence transcriptional outputs, including the binding of transcription factors to specific DNA sequences, the role of cofactors in facilitating their function, and the complex interplay within regulatory landscapes. The authors propose that a quantitative, mechanistically informed model of transcriptional regulation is essential for ultimately understanding the cis-regulatory code.
Article
Endocrinology & Metabolism
Antoine Weihs, Layal Chaker, Tiphaine C. Martin, Kim V. E. Braun, Purdey J. Campbell, Simon R. Cox, Myriam Fornage, Christian Gieger, Hans J. Grabe, Harald Grallert, Sarah E. Harris, Brigitte Kuehnel, Riccardo E. Marioni, Nicholas G. Martin, Daniel L. McCartney, Allan F. McRae, Christa Meisinger, Joyce B. J. van Meurs, Jana Nano, Matthias Nauck, Annette Peters, Holger Prokisch, Michael Roden, Elizabeth Selvin, Marian Beekman, Diana van Heemst, Eline P. Slagboom, Brenton R. Swenson, Adrienne Tin, Pei-Chien Tsai, Andre Uitterlinden, W. Edward Visser, Henry Voelzke, Melanie Waldenberger, John P. Walsh, Anna Koettgen, Scott G. Wilson, Robin P. Peeters, Jordana T. Bell, Marco Medici, Alexander Teumer
Summary: Novel associations between thyroid hormones and DNA methylation were discovered, advancing our understanding of thyroid hormone action particularly related to KLF9. This study demonstrates the utility of integrating EWAS with other -omics data for unraveling thyroid hormone signaling in humans.
Article
Multidisciplinary Sciences
Sarah E. Pierce, Jeffrey M. Granja, William J. Greenleaf
Summary: The Spear-ATAC method enables simultaneous reading of chromatin accessibility profiles and sgRNA sequences from single cells, revealing the dynamic epigenetic responses to regulatory perturbations in cancer cells. Dynamics of transcription factor binding can drive epigenetic states, leading to a diversity of phenotypes.
NATURE COMMUNICATIONS
(2021)
Article
Biochemistry & Molecular Biology
Veronika te Boekhorst, Liying Jiang, Marius Mahlen, Maaike Meerlo, Gina Dunkel, Franziska C. Durst, Yanjun Yang, Herbert Levine, Boudewijn M. T. Burgering, Peter Friedl
Summary: This article studies the molecular mechanisms of cancer cell invasion and metastasis under hypoxic conditions and identifies calpain-2 as a key regulator of the transition from collective to amoeboid dissemination in breast and head and neck carcinoma cells. The study reveals that hypoxia induces calpain-2-mediated amoeboid conversion by deactivating beta 1 integrins. Targeted intervention of calpain-2 activity can restore normal cell phenotype and prevent lung metastasis.
Article
Biochemistry & Molecular Biology
Srinath Muralidharan, Sarthak Sahoo, Aryamaan Saha, Sanjay Chandran, Sauma Suvra Majumdar, Susmita Mandal, Herbert Levine, Mohit Kumar Jolly
Summary: Research analysis reveals diverse associations between cancer cells' EMT status and metabolic pathways, showing that EMT is generally positively correlated with glycolysis but negatively correlated with oxidative phosphorylation and fatty acid metabolism. Additionally, higher levels of EMT and glycolysis predict a worse prognosis in many cancers.
Editorial Material
Multidisciplinary Sciences
Herbert Levine
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
(2022)
Article
Biochemistry & Molecular Biology
Samuel A. Vilchez Mercedes, Federico Bocci, Mona Ahmed, Ian Eder, Ninghao Zhu, Herbert Levine, Jose N. Onuchic, Mohit Kumar Jolly, Pak Kin Wong
Summary: In this study, the researchers used a combination of immunocytochemistry, single cell biosensors, and computational modeling to show that the transcription factor Nrf2 functions as a phenotypic stability factor for hybrid epithelial/mesenchymal cells during collective cancer migration. They also demonstrated that Nrf2 and EMT signaling are spatially coordinated near the leading edge, and that the Nrf2-EMT-Notch network enhances the expression of certain genes associated with the formation of leader cells and protruding tips.
FRONTIERS IN MOLECULAR BIOSCIENCES
(2022)
Article
Chemistry, Physical
Wen Jia, Atchuta Srinivas Duddu, Mohit Kumar Jolly, Herbert Levine
Summary: Biological cells can have different phenotypes determined by genetic networks, and the creation of landscapes is a popular way to represent these states. It is commonly believed that the landscape provides direct information about the state-to-state transition rates. However, this study shows that there is no direct correlation between the properties of the landscape and the corresponding transition rates.
JOURNAL OF PHYSICAL CHEMISTRY B
(2022)
Article
Physics, Multidisciplinary
David A. Kessler, Herbert Levine
Summary: Drug persistence is an important phenomenon in cancer treatment, and finding effective strategies to eliminate persister cells is crucial.
PHYSICAL REVIEW LETTERS
(2022)
Article
Multidisciplinary Sciences
M. Ali Al-Radhawi, Shubham Tripathi, Yun Zhang, Eduardo D. Sontag, Herbert Levine
Summary: In this paper, the authors investigate the complex interactions between epigenetic marks, external signals, and gene-regulatory elements that lead to the emergence and transitions between distinct phenotypes in isogenic cells. They propose a mathematical modeling framework that considers both local and global competition effects between antagonistic epigenetic regulators, as well as the influence of local transcription factors. Applying this approach to experimental findings on the epithelial-mesenchymal transition, they are able to explain the observed data and provide verifiable predictions.
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
(2022)
Article
Multidisciplinary Sciences
Shubham Tripathi, David A. Kessler, Herbert Levine
Summary: Regulatory network models have proven to be effective tools for understanding and predicting cell-fate choice. This study shows that minimally frustrated networks can exhibit simple, low-dimensional steady-state behavior even in large and complex networks. These findings provide a theoretical explanation for the success of network models in biology and the challenges in network inference.
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
(2022)
Article
Multidisciplinary Sciences
Cristian Caranica, Mingyang Lu
Summary: One major challenge in systems biology is to understand the collective functions and control dynamics of genes in a gene regulatory network (GRN). Existing methods for model reduction often require detailed mathematical descriptions and parameters, which may not be available. Here, we propose a data-driven method, SacoGraci, for coarse-graining large GRNs using ensemble-based modeling, dimensionality reduction, and gene circuit optimization. SacoGraci only requires network topology as input and is robust against errors in GRNs. It has been tested and validated with synthetic, literature-based, and bioinformatics-derived GRNs.
Article
Multidisciplinary Sciences
Benjamin Clauss, Mingyang Lu
Summary: This article introduces a new computational framework that allows systematic, high-throughput, and quantitative evaluation of the contribution of small transcriptional regulatory circuit motifs and their coupling to the overall functions of a biological system. By applying this method, the authors identified four-node gene circuits, circuit motifs, and motif coupling responsible for various gene expression state distributions, including those derived from single-cell RNA sequencing data. They also discovered seven major classes of four-node circuits through clustering analysis of state distributions. Additionally, the method was used to establish phenomenological models of gene circuits driving human neuron differentiation, uncovering important biologically relevant regulatory interactions. This study will provide insights into a better understanding of gene regulatory mechanisms in creating and maintaining cellular states.
Article
Multidisciplinary Sciences
Paras Jain, Sophia Corbo, Kulsoom Mohammad, Sarthak Sahoo, Santhalakshmi Ranganathan, Jason T. George, Herbert Levine, Joseph Taube, Michael Toneff, Mohit Kumar Jolly
Summary: Epithelial-mesenchymal transition (EMT) and its reverse mesenchymal-epithelial transition (MET) play crucial roles in embryonic development, wound healing, and cancer metastasis. While short-term EMT induction can lead to reversible phenotypic changes, long-term EMT induction is often associated with irreversibility. In this study, we demonstrate that the phenotypic changes observed in MCF10A cells during long-term EMT induction by TGF-beta can in fact have longer timescales of reversibility. We also propose a mathematical model that explains how the epigenetic memory gained during long-term EMT induction can slow down the recovery to the epithelial state after TGF-beta withdrawal.
JOURNAL OF THE ROYAL SOCIETY INTERFACE
(2023)
Article
Physics, Fluids & Plasmas
Kevin Ng Chau, Jason T. George, Jose N. Onuchic, Xingcheng Lin, Herbert Levine
Summary: An affinity-based model for TCR-pMHC binding was studied, showing that the binding energy distribution depends on the number of contacts and the topology of the contact map. It was also quantified how neoantigens with mutations in sites with higher contacts are recognized at a higher rate.
Article
Geriatrics & Gerontology
Siao Ye, Kevin Sun, Duong Huynh, Huy Q. Phi, Brian Ko, Bin Huang, Reza Hosseini Ghomi
Summary: This study evaluated the diagnostic accuracy and ability of a computerized cognitive testing battery (BrainCheck) to distinguish between dementia, mild cognitive impairment (MCI), and normal cognition (NC). The results showed that BrainCheck was able to effectively distinguish between these diagnoses and could potentially serve as a reliable tool for early detection of cognitive impairment.
Article
Physics, Multidisciplinary
Pedram Esfahani, Herbert Levine, Mrinmoy Mukherjee, Bo Sun
Summary: Directed cell migration is crucial in various physiological and pathophysiological processes. This study investigates the migration of breast cancer cells in the presence of both contact guidance and a chemoattractant gradient. The results reveal that the microstructure of the extracellular matrix plays a complex role in cell chemotaxis. Coherent extracellular matrix fibers significantly enhance chemotaxis efficiency when contact guidance is parallel to the chemical gradient, while cells exploit ECM disorder to locate paths for chemotaxis when contact guidance is perpendicular to the chemical gradient.
PHYSICAL REVIEW RESEARCH
(2022)
Article
Oncology
Hiroko Masuda, Kenichi Harano, Sakiko Miura, Ying Wang, Yuko Hirota, Oi Harada, Mohit Kumar Jolly, Yuki Matsunaga, Bora Lim, Anita L. Wood, Napa Parinyanitikul, Hee Jin Lee, Gyungyub Gong, Jason T. George, Herbert Levine, Jangsoon Lee, Xiaoping Wang, Anthony Lucci, Arvind Rao, Brock L. Schweitzer, O. Rayne Lawrence, Robert S. Seitz, Stephan W. Morris, David R. Hout, Seigo Nakamura, Savitri Krishnamurthy, Naoto T. Ueno
Summary: The study found that TNBC molecular subtype and IM signature frequently change after NST, and the results suggest that EMT is promoted in the changed subtypes.
JCO PRECISION ONCOLOGY
(2022)