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The dynamic immune behavior of primary and metastatic ovarian carcinoma

npj Precision Oncology 2025年第1期9卷 1-12页

作者： Stur, Elaine Peng, Fuduan Teng, Pang-Ning Bayraktar, Emine Hu, Min Corvigno, Sara Brown, David J. Lee, Sanghoon Moore, Kathleen N. Bateman, Nicholas W. Darcy, Kathleen M. Maxwell, George L. P. Conrads, Thomas Sahni, Nidhi Vázquez-García, Ignacio Shah, Sohrab P. Celestino, Joseph D. Fleming, Nicole Navin, Nicholas E. Wang, Linghua Sood, Anil K. Department of Gynecologic Oncology and Reproductive Medicine The University of Texas MD Anderson Cancer Center Houston TX United States Department of Genomic Medicine The University of Texas MD Anderson Cancer Center Houston TX United States Gynecologic Cancer Center of Excellence The Henry M. Jackson Foundation for the Advancement of Military Medicine Inc. Walter Reed National Military Medical Center Bethesda 20889 MD United States Department of Gynecologic Surgery and Obstetrics Uniformed Services University of the Health Sciences Walter Reed National Military Medical Center Bethesda MD United States Department of Genetics The University of Texas MD Anderson Cancer Center Houston TX United States Obstetrics and Gynecology Stephenson Cancer Center Stephenson Cancer Center at the University of Oklahoma Health Sciences Center/Sarah Cannon Research Institute Oklahoma City OK United States Women’s Health Integrated Research Center Women’s Service Line Inova Health System Falls Church VA United States Department of Epigenetics and Molecular Carcinogenesis The University of Texas MD Anderson Cancer Center Baylor College of Medicine Houston TX United States Department of Bioinformatics and Computational Biology The University of Texas MD Anderson Cancer Center Houston TX United States Quantitative and Computational Biosciences Program Baylor College of Medicine Houston TX United States Computational Oncology Department of Epidemiology and Biostatistics Memorial Sloan Kettering Cancer Center New York NY United States The Halvorsen Center for Computational Oncology Memorial Sloan Kettering Cancer Center Boston MA United States Irving Institute for Cancer Dynamics Columbia University Cambridge 10027 MA United States Department of Systems Biology The University of Texas MD Anderson Cancer Center Houston MA United States The James P. Allison Institute The University of Texas MD Anderson Cancer Center Houston 77030 TX United States The Institute for Data Sc

Patients with high-grade serous ovarian carcinoma (HGSC) are usually diagnosed with advanced-stage disease, and the tumors often have immunosuppressive characteristics. Together, these factors are important for disease progression, drug resistance, and mortality. In this study, we used a combination of single-cell sequencing and spatial transcriptomics to identify the molecular mechanisms that lead to immunosuppression in HGSC. Primary tumors consistently showed a more active immune microenvironment than did omental tumors. In addition, we found that untreated primary tumors were mostly populated by dysfunctional CD4 and CD8 T cells in later stages of differentiation;this, in turn, was correlated with expression changes in the interferon α and γ pathways in epithelial cells, showing that cross-communication between the epithelial and immune compartments is important for immune suppression in HGSC. These findings could have implications for the design of clinical trials with immune-modulating drugs. © The Author(s) 2025.

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Unexpected failure rates for modular assembly of engineered zinc fingers (vol 5, pg 374, 2008)

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NATURE METHODS 2008年第6期5卷 575-575页

作者： Ramirez, Cherie L. Foley, Jonathan E. Wright, David A. Mueller-Lerch, Felix Rahman, Shamim H. Cornu, Tatjana I. Winfrey, Ronnie J. Sander, Jeffry D. Fu, Fengli Townsend, Jeffrey A. Cathomen, Toni Voytas, Daniel F. Joung, J. Keith These authors contributed equally to this work. These authors contributed equally to this work. Department of Genetics Development and Cell Biology Iowa State University 1035A Roy J. Carver Co-Lab Ames Iowa 50011 USA. Charité Medical School Institute of Virology Hindenburgdamm 27 D-12203 Berlin Germany. Charité Medical School Institute of Virology Hindenburgdamm 27 D-12203 Berlin Germany. Charité Medical School Institute of Virology Hindenburgdamm 27 D-12203 Berlin Germany. Department of Genetics Development and Cell Biology Iowa State University 1035A Roy J. Carver Co-Lab Ames Iowa 50011 USA. Interdepartmental Graduate Program in Bioinformatics and Computational Biology 2114 Molecular Biology Building Iowa State University Ames Iowa 50011 USA. Interdepartmental Graduate Program in Bioinformatics and Computational Biology 2114 Molecular Biology Building Iowa State University Ames Iowa 50011 USA. Department of Genetics Development and Cell Biology Iowa State University 1035A Roy J. Carver Co-Lab Ames Iowa 50011 USA. Charité Medical School Institute of Virology Hindenburgdamm 27 D-12203 Berlin Germany. Department of Genetics Development and Cell Biology Iowa State University 1035A Roy J. Carver Co-Lab Ames Iowa 50011 USA. Department of Pathology Harvard Medical School Boston Massachusetts 02115 USA.

A letter to the editor is presented in response to an article on zinc fingers in a previous issue.

关键词： LETTERS to the editor ZINC

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Context-dependent gene regulatory network reveals regulation dynamics and cell trajectories using unspliced transcripts

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Briefings in bioinformatics 2023年第2期24卷 bbac633-bbac633页

作者： Tu, Yueh-Hua Juan, Hsueh-Fen Huang, Hsuan-Cheng The Bioinformatics Program Taiwan International Graduate Program Academia Sinica Taiwan Department of Life Science Center for Computational and Systems Biology National Taiwan University Taiwan Institute of Biomedical Informatics National Yang Ming Chiao Tung University Taiwan

Gene regulatory networks govern complex gene expression programs in various biological phenomena, including embryonic development, cell fate decisions and oncogenesis. Single-cell techniques are increasingly being used to study gene expression, providing higher resolution than traditional approaches. However, inferring a comprehensive gene regulatory network across different cell types remains a challenge. Here, we propose to construct context-dependent gene regulatory networks (CDGRNs) from single-cell RNA sequencing data utilizing both spliced and unspliced transcript expression levels. A gene regulatory network is decomposed into subnetworks corresponding to different transcriptomic contexts. Each subnetwork comprises the consensus active regulation pairs of transcription factors and their target genes shared by a group of cells, inferred by a Gaussian mixture model. We find that the union of gene regulation pairs in all contexts is sufficient to reconstruct differentiation trajectories. Functions specific to the cell cycle, cell differentiation or tissue-specific functions are enriched throughout the developmental process in each context. Surprisingly, we also observe that the network entropy of CDGRNs decreases along differentiation trajectories, indicating directionality in differentiation. Overall, CDGRN allows us to establish the connection between gene regulation at the molecular level and cell differentiation at the macroscopic level. © The Author(s) 2023.

关键词： Gaussian mixture model gene regulatory network single-cell RNA sequencing trajectory analysis

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Calibrated Langevin-dynamics simulations of intrinsically disordered proteins

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Physical Review E 2014年第4期90卷 042709-042709页

作者： W. Wendell Smith Po-Yi Ho Corey S. O'Hern Department of Physics Yale University New Haven Connecticut 06520-8120 USA Integrated Graduate Program in Physical and Engineering Biology Yale University New Haven Connecticut 06520-8114 USA Department of Mechanical Engineering and Materials Science Yale University New Haven Connecticut 06520-8286 USA Department of Applied Physics Yale University New Haven Connecticut 06520-8267 USA Program in Computational Biology and Bioinformatics Yale University New Haven Connecticut 06520 USA

We perform extensive coarse-grained (CG) Langevin dynamics simulations of intrinsically disordered proteins (IDPs), which possess fluctuating conformational statistics between that for excluded volume random walks and collapsed globules. Our CG model includes repulsive steric, attractive hydrophobic, and electrostatic interactions between residues and is calibrated to a large collection of single-molecule fluorescence resonance energy transfer data on the interresidue separations for 36 pairs of residues in five IDPs: α−, β−, and γ-synuclein, the microtubule-associated protein τ, and prothymosin α. We find that our CG model is able to recapitulate the average interresidue separations regardless of the choice of the hydrophobicity scale, which shows that our calibrated model can robustly capture the conformational dynamics of IDPs. We then employ our model to study the scaling of the radius of gyration with chemical distance in 11 known IDPs. We identify a strong correlation between the distance to the dividing line between folded proteins and IDPs in the mean charge and hydrophobicity space and the scaling exponent of the radius of gyration with chemical distance along the protein.

关键词： LANGEVIN equations SIMULATION methods & models CONFORMATIONAL analysis MICROTUBULE-associated proteins HYDROPHOBIC compounds

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SARS-CoV-2 surveillance of wastewater in small rural communities identifies lack of vaccine coverage as influence of omicron outbreak

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Water Research 2025年 283卷

作者： Solana Narum Thibault Stalder Benjamin Ridenhour Erik R. Coats Bioinformatics and Computational Biology Graduate Program (BCB) University of Idaho 875 Perimeter Drive MS 1103 Moscow ID 83844 United States Institute for Modeling Collaboration and Innovation (IMCI) University of Idaho 875 Perimeter Drive MS 1122 Moscow ID 83844 United States Department of Biological Sciences University of Idaho 875 Perimeter Drive MS 3051 Moscow ID 83844 United States Institute for Interdisciplinary Data Sciences (IIDS) University of Idaho 875 Perimeter Drive MS 3051 Moscow ID 83844 United States Department of Mathematics and Statistical Science University of Idaho 875 Perimeter Drive MS 1103 Moscow ID 83844 United States Department of Civil and Environmental Engineering University of Idaho 875 Perimeter Drive MS 1022 Moscow ID 83844 United States

Wastewater-based epidemiology (WBE) can provide critical early warnings to aid public health, which can be particularly beneficial in rural communities with limited access to health care. Spikes of SARS-CoV-2 RNA concentration in wastewater have been used to represent infections in a community, but wastewater holds a wealth of information that has not been explored yet. The objectives of this research were to expand the use of WBE to 1) determine the dynamic of SARS-CoV-2 variants in rural communities, and 2) evaluate the relationship between community vaccination status and the outbreak of a variant. We quantified the concentration of SARS-CoV-2 RNA, as well as specific mutations that are consistent with Delta and Omicron in influent raw wastewater samples collected from wastewater treatment facilities (WWTFs) for five populations with <1000 residents and one larger population in Latah County, ID. A binomial generalized linear model using the percent of the population with protection against Omicron from the initial vaccines and the booster shot was able to predict the probability of an uptick in Omicron concentration in wastewater with an accuracy of 0.96. Evaluation of vaccination data indicate that the spike in Omicron infections in December 2021 in the studied towns was linked to low levels of population protection from the initial shots of the COVID-19 vaccine against Omicron infection and limited uptake of booster shots in these communities. Despite difficulties with applying WBE in rural regions, this study shows that beyond evaluating spikes of viral infections, WBE can be used to evaluate the effect of a population’s vaccine coverage on SARS-CoV-2 variant dynamics.

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Decomposition of dynamic transcriptomic responses during effector-triggered immunity reveals conserved responses in two distinct plant cell populations

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Plant Communications 2024年第8期5卷 1-17页

作者： Xiaotong Liu Daisuke Igarashi Rachel A.Hillmer Thomas Stoddard You Lu Kenichi Tsuda Chad L.Myers Fumiaki Katagiri Department of Plant and Microbial Biology University of Minnesota-Twin CitiesSt PaulMN 55108USA Department of Computer Science and Engineering University of Minnesota-Twin CitiesMinneapolisMN 55455USA Bioinformatics and Computational Biology Graduate Program University of Minnesota-Twin CitiesMinneapolisMN 55455USA Institute for Innovation Ajinomoto Co.Inc.KawasakiJapan State Key Laboratory of Agricultural Microbiology Hubei Hongshan LaboratoryHubei Key Lab of Plant PathologyCollege of Plant Science and TechnologyHuazhong Agricultural UniversityWuhan 430070China Present address:225 S 6th St MinneapolisMN 55402USA Present address:Biotalys Inc.2520 Meridian Parkway Suite 480DurhamNC 27713USA Present address:Life Sciences Institute and Department of Cell and Developmental Biology University of Michigan Medical SchoolAnn ArborMI 48109USA

Rapid plant immune responses in the appropriate cells are needed for effective defense against *** transcriptome analysis is often used to describe overall immune responses,collection of transcriptome data with sufficient resolution in both space and time is *** reanalyzed public Arabidopsis time-course transcriptome data obtained after low-dose inoculation with a Pseudomonas syringae strain expressing the effector AvrRpt2,which induces effector-triggered immunity in ***-peak time-course patterns are prevalent among thousands of upregulated *** implemented a multicompartment modeling approach to decompose the double-peak pattern into two single-peak patterns for each *** decomposed peaks reveal an“echoing”pattern:the peak times of the first and second peaks correlate well across most upregulated *** demonstrated that the two peaks likely represent responses of two distinct cell populations that respond either cell autonomously or indirectly to ***,the peak decomposition has extracted spatial information from the time-course *** echoing pattern also indicates a conserved transcriptome response with different initiation times between the two cell populations despite different elicitor types.A gene set highly overlapping with the conserved gene set is also upregulated with similar kinetics during pattern-triggered *** of a WRKY network via different entry-point WRKYs can explain the similar but not identical transcriptome responses elicited by different elicitor *** discuss potential benefits of the properties of the WRKY activation network as an immune signaling network in light of pressure from rapidly evolving pathogens.

关键词： Arabidopsis Pseudomonas syringae plant immune response multi-compartment model WRKY transcription factors resilient immune signaling network

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SYSTEMS biology IN BARLEY POWDERY MILDEW INTERACTIONS

SYSTEMS BIOLOGY IN BARLEY POWDERY MILDEW INTERACTIONS

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The 13th International Cereal Rusts and Powdery Mildews Conference(第13届国际禾谷类锈病与白粉病大会)

作者： Roger WISE Priyanka SURANA Greg FUERST Ruo XU Dan NETTLETON Divya MISTRY Julie DICKERSON Lin WANG Tom BRUTNELL Department of Plant Pathology and Microbiology Center for Plant Responses to Environmental StressesIowa State UniversityAmesIowa 50011USA Department of Statistics Iowa State UniversityAmesIowa 50011USA Bioinformatics and Computational Biology Graduate ProgramIowa State UniversityAmesIowa 50011USA Bioinformatics and Computational Biology Graduate ProgramIowa State UniversityAmesIowa 50011USA Bioinformatics and Computational Biology Graduate Program Iowa State UniversityAmesIowa 50011USA Department of Plant Pathology and MicrobiologyCenter for Plant Responses to Environmental StressesIowa State UniversityAmesIowa 50011USA Crop and Insect Genetics Genomicsand Informatics Research UnitU.S.Department of Agriculture-Agricultural Research ServiceIowa State UniversityAmesIowa 50011USA Department of Plant Pathology and Microbiology Center for Plant Responses to Environmental StressesIowa State UniversityAmesIowa 50011USA Department of StatisticsIowa State UniversityAmesIowa 50011USA Bioinformatics and Computational Biology Graduate ProgramIowa State UniversityAmesIowa 50011USA Bioinformatics and Computational Biology Graduate Program Iowa State UniversityAmesIowa 50011USA Crop and Insect GeneticsGenomicsand Informatics Research UnitU.S.Department of Agriculture-Agricultural Research ServiceIowa State UniversityAmesIowa 50011USA Department of Electrical and Computer Engineering Iowa State UniversityAmesIowa 50011USA Boyce Thompson Institute for Plant ResearchCornell UniversityIthacaNY

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Connecting polymer collapse and the onset of jamming

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Physical Review E 2024年第3期109卷 034406-034406页

作者： Alex T. Grigas Aliza Fisher Mark D. Shattuck Corey S. O'Hern Graduate Program in Computational Biology and Bioinformatics Yale University New Haven Connecticut 06520 USA Integrated Graduate Program in Physical and Engineering Biology Yale University New Haven Connecticut 06520 USA Department of Mechanical Engineering and Materials Science Yale University New Haven Connecticut 06520 USA Benjamin Levich Institute and Physics Department The City College of New York New York New York 10031 USA Department of Physics Yale University New Haven Connecticut 06520 USA Department of Applied Physics Yale University New Haven Connecticut 06520 USA

Previous studies have shown that the interiors of proteins are densely packed, reaching packing fractions that are as large as those found for static packings of individual amino-acid-shaped particles. How can the interiors of proteins take on such high packing fractions given that amino acids are connected by peptide bonds and many amino acids are hydrophobic with attractive interactions? We investigate this question by comparing the structural and mechanical properties of collapsed attractive disk-shaped bead-spring polymers to those of three reference systems: static packings of repulsive disks, of attractive disks, and of repulsive disk-shaped bead-spring polymers. We show that the attractive systems quenched to temperatures below the glass transition T≪Tg and static packings of both repulsive disks and bead-spring polymers possess similar interior packing fractions. Previous studies have shown that static packings of repulsive disks are isostatic at jamming onset, i.e., the number of interparticle contacts Nc matches the number of degrees of freedom, which strongly influences their mechanical properties. We find that repulsive polymer packings are hypostatic at jamming onset (i.e., with fewer contacts than degrees of freedom) but are effectively isostatic when including stabilizing quartic modes, which give rise to quartic scaling of the potential energy with displacements along these modes. While attractive disk and polymer packings are often considered hyperstatic with excess contacts over the isostatic number, we identify a definition for interparticle contacts for which they can also be considered as effectively isostatic. As a result, we show that the mechanical properties (e.g., scaling of the potential energy with excess contact number and low-frequency contribution to the density of vibrational modes) of weakly attractive disk and polymer packings are similar to those of isostatic repulsive disk and polymer packings. Our results demonstrate that static

关键词： Jamming Polymer folding Protein folding Single polymer chains

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Continuity Equation of Left Invariant Gauge Field in Quantum Genotype Of Deltacron

SSRN

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SSRN 2022年

作者： Hannongbua, Supot Kanjamapornkul, Kabin Rungrotmongkol, Thanyada Department of Chemistry Faculty of Science Chulalongkorn University Bangkok10330 Thailand Biocatalyst and Environmental Biotechnology Research Unit Department of Biochemistry Faculty of Science Chulalongkorn University Bangkok10330 Thailand Program in Bioinformatics and Computational Biology Graduate School Chulalongkorn University Bangkok10330 Thailand

The continuity equation for the invariant gauge field of Deltacron was investigated from the replication and recombination of Delta with Omicron. The new definition of left translation of the invariant gauge field in the quantum genotype of virus and host cell was introduced. The Yang-Mills field in genetic code is an induced curvature in the parallel transport of a unified field between hydrogen bonding between three types of biomolecules. where we defined the invariant gauge field in quantum genotype. This issue allows us to identify the Poincare duality between the nteraction between the behavior field of gene expression in parasitism state and in the curvature of connection in fiber space of Spike protein folding molecule. The Chern Simons current is the anti-self-dual state of mutation between two types of interactive behavior fields in The recombination process of Deltacron was used to plot the Yang-Mills curvature directly from the underlying genetic codes. Further analysis shows that the difference between the tensor correlation with various times of Deltacron the change slope of Omicron BA.1 to the flat curve of the network correlation and closedness centrality of amino acids in receptor binding domain of Spike protein. © 2022, The Authors. All rights reserved.

关键词： Gene expression

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EQTL AND MUTATIONAL ANALYSIS OF NB-LRR MEDIATED IMMUNITY TO POWDERY MILDEW

EQTL AND MUTATIONAL ANALYSIS OF NB-LRR MEDIATED IMMUNITY TO ...

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The 13th International Cereal Rusts and Powdery Mildews Conference(第13届国际禾谷类锈病与白粉病大会)

作者： Roger WISE Priyanka SURANA Greg FUERST Ruo XU Divya MISTRY Julie DICKERSON Dan NETTLETON Department of Statistics Iowa State UniversityAmesIowa 50011 Department of Plant Pathology and Microbiology Center for Plant Responses to Environmental StressesIowa State UniversityAmesIowa 50011 Department of StatisticsIowa State UniversityAmesIowa 50011 Bioinformatics and Computational Biology Graduate ProgramIowa State UniversityAmesIowa 50011 Department of Electrical and Computer Engineering Iowa State UniversityAmesIowa 50011USA Bioinformatics and Computational Biology Graduate ProgramIowa State UniversityAmesIowa 50011 Bioinformatics and Computational Biology Graduate Program Iowa State UniversityAmesIowa 50011 Department of Plant Pathology and MicrobiologyCenter for Plant Responses to Environmental StressesIowa State UniversityAmesIowa 50011 Department of Plant Pathology and Microbiology Center for Plant Responses to Environmental StressesIowa State UniversityAmesIowa 50011 Bioinformatics and Computational Biology Graduate Program Iowa State UniversityAmesIowa 50011 Crop and Insect GeneticsGenomicsand Informatics Research UnitU.S.Department of Agriculture-Agricultural Research ServiceIowa State UniversityAmesIowa 50011 Crop and Insect Genetics Genomicsand Informatics Research UnitU.S.Department of Agriculture-Agricultural Research ServiceIowa State UniversityAmesIowa 50011

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