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The emerging role of mesenchymal stem cell-derived extracellular vesicles to ameliorate hippocampal NLRP3 inflammation induced by binge-like ethanol treatment in adolescence

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Neural Regeneration Research 2025年第4期20卷 1153-1163页

作者： Susana Mellado María JoséMorillo-Bargues Carla Perpiñá-Clérigues Francisco García-García Victoria Moreno-Manzano Consuelo Guerri María Pascual Department of Physiology School of Medicine and DentistryUniversity of ValenciaValenciaSpain bioinformatics and Biostatistics Unit Príncipe Felipe Research CenterValenciaSpain Neuronal and Tissue Regeneration Laboratory Príncipe Felipe Research CenterValenciaSpain

Our previous studies have reported that activation of the NLRP3(NOD-,LRR-and pyrin domain-containing protein 3)-inflammasome complex in ethanol-treated astrocytes and chronic alcohol-fed mice could be associated with neuroinflammation and brain *** stem cell-derived extracellular vesicles(MSC-EVs)have been shown to restore the neuroinflammatory response,along with myelin and synaptic structural alterations in the prefrontal cortex,and alleviate cognitive and memory dysfunctions induced by binge-like ethanol treatment in adolescent *** the therapeutic role of the molecules contained in mesenchymal stem cell-derived extracellular vesicles,the present study analyzed whether the administration of mesenchymal stem cell-derived extracellular vesicles isolated from adipose tissue,which inhibited the activation of the NLRP3 inflammasome,was capable of reducing hippocampal neuroinflammation in adolescent mice treated with binge *** demonstrated that the administration of mesenchymal stem cell-derived extracellular vesicles ameliorated the activation of the hippocampal NLRP3 inflammasome complex and other NLRs inflammasomes(e.g.,pyrin domain-containing 1,caspase recruitment domain-containing 4,and absent in melanoma 2,as well as the alterations in inflammatory genes(interleukin-1β,interleukin-18,inducible nitric oxide synthase,nuclear factor-kappa B,monocyte chemoattractant protein-1,and C–X3–C motif chemokine ligand 1)and miRNAs(miR-21a-5p,miR-146a-5p,and miR-141-5p)induced by binge-like ethanol treatment in adolescent *** analysis further revealed the involvement of miR-21a-5p and miR-146a-5p with inflammatory target genes and NOD-like receptor signaling *** together,these findings provide novel evidence of the therapeutic potential of MSC-derived EVs to ameliorate the hippocampal neuroinflammatory response associated with NLRP3 inflammasome activation induced by binge drinking in adolescence.

关键词： adolescence binge-like ethanol treatment extracellular vesicles hippocampus mesenchymal stem cells neuroinflammation NOD-,LRR-and pyrin domain-containing protein 3(NLRP3)

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Streamlined and on-demand preparation of mRNA products on a universal integrated platform

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Microsystems & Nanoengineering 2023年第4期9卷 119-128页

作者： Hongjuan Wei Zhen Rong Liyan Liu Ye Sang Jing Yang Shengqi Wang bioinformatics center of AMMS Beijing 100850P.R.China

Vaccines are used to protect human beings from various *** vaccines simplify the development process and reduce the production cost of conventional vaccines,making it possible to respond rapidly to acute and severe diseases,such as coronavirus disease *** this study,a universal integrated platform for the streamlined and ondemand preparation of mRNA products directly from DNA templates was *** DNA templates were amplified in vitro by a polymerase chain reaction module and transcribed into mRNA sequences,which were magnetically purified and encapsulated in lipid *** an initial example,enhanced green fluorescent protein(eGFP)was used to test the *** expression capacity and efficiency of the products were evaluated by transfecting them into HEK-293T *** batch production rate was estimated to be 200–300μg of eGFP mRNA in 8 ***,an mRNA vaccine encoding the receptor-binding domain(RBD)of the severe acute respiratory syndrome coronavirus 2(SARS-CoV-2)spike protein was produced by this *** proposed integrated platform shows advantages for the universal and on-demand preparation of mRNA products,offering the potential to facilitate broad access to mRNA technology and enable the development of mRNA products,including the rapid supply of new mRNA-based vaccines in pandemic situations and personalized mRNA-based therapies for oncology and chronic infectious diseases,such as viral hepatitis and acquired immune deficiency syndrome.

关键词： preparation template offering

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VASC: Dimension Reduction and Visualization of Single-cell RNA-seq Data by Deep Variational Autoencoder

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Genomics, Proteomics & bioinformatics 2018年第5期16卷 320-331页

作者： Dongfang Wang Jin Gu MOE Key Laboratory of bioinformatics BNRIST Bioinformatics Division & Center for Synthetic and Systems BiologyDepartment of Automation Tsinghua University

Single-cell RNA sequencing(scRNA-seq) is a powerful technique to analyze the transcriptomic heterogeneities at the single cell level. It is an important step for studying cell subpopulations and lineages, with an effective low-dimensional representation and visualization of the original scRNA-Seq data. At the single cell level, the transcriptional fluctuations are much larger than the average of a cell population, and the low amount of RNA transcripts will increase the rate of technical dropout events. Therefore, scRNA-seq data are much noisier than traditional bulk RNA-seq data. In this study, we proposed the deep variational autoencoder for scRNA-seq data(VASC), a deep multi-layer generative model, for the unsupervised dimension reduction and visualization of scRNA-seq data. VASC can explicitly model the dropout events and find the nonlinear hierarchical feature representations of the original data. Tested on over 20 datasets, VASC shows superior performances in most cases and exhibits broader dataset compatibility compared to four state-of-the-art dimension reduction and visualization methods. In addition, VASC provides better representations for very rare cell populations in the 2D visualization. As a case study, VASC successfully re-establishes the cell dynamics in pre-implantation embryos and identifies several candidate marker genes associated with early embryo development. Moreover, VASC also performs well on a 10× Genomics dataset with more cells and higher dropout rate.

关键词： Single cell RNA sequencing Deep variational autoencoder Dimension reduction Visualization Dropout

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Structured Learning in Biological Domain

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Journal of Systems Science and Systems Engineering 2020年第4期29卷 440-453页

作者： Canh Hao Nguyen bioinformatics center Instute for Chemical ResearchKyoto UniversityUjiKyotoJapan

Biological domain has been blessed with more and more data from biotechnologies as well as data integration *** the renaissance of machine learning and artificial intelligence,there is so much promise of data-driven biological knowledge ***,it is not straight forward due to the complexity of the domain knowledge hidden in the *** any level,be it atoms,molecules,cells or organisms,there are rich interdependencies among biological *** learning approaches in this domain usually involves analyzing interdependency structures encoded in graphs and related *** this report,we review our work in developing new Machine Learning methods for these applications with improved performances in comparison with state-of-the-art *** show how the networks among biological components can be used to predict properties.

关键词： Structured learning sparse modeling systems biology deep learning

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A homing rescue gene drive with multiplexed gRNAs reaches high frequency in cage populations but generates functional resistance

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Journal of Genetics and Genomics 2024年第8期51卷 836-843页

作者： Shibo Hou Jingheng Chen Ruobing Feng Xuejiao Xu Nan Liang Jackson Champer center for bioinformatics Center for Life SciencesSchool of Life SciencesPeking UniversityBeijing 100871China

CRISPR homing gene drives have considerable potential for managing populations of medically and agriculturally significant *** operate by Cas9 cleavage followed by homology-directed repair,copying the drive allele to the wild-type chromosome and thus increasing in frequency and spreading throughout a ***,resistance alleles formed by end-joining repair pose a significant *** address this,we create a homing drive targeting the essential hairy gene in Drosophila *** resistance alleles are recessive lethal,while drive carriers have a recoded“rescue”version of *** drive inheritance rate is moderate,and multigenerational cage studies show drive spread to 96%–97%of the ***,the drive does not reach 100%due to the formation of functional resistance alleles despite using four *** alleles have a large deletion but likely utilize an alternate start ***,revised designs targeting more essential regions of a gene may be necessary to avoid such functional *** of the rescue element’s native 3'UTR with a homolog from another species increases drive inheritance by 13%–24%.This was possibly because of reduced homology between the rescue element and surrounding genomic DNA,which could also be an important design consideration for rescue gene drives.

关键词： Genedrive Homing drive Rescueelement Population modification Multiplexed gRNAs Resistance alleles Cage study

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DIProT:A deep learning based interactive toolkit for efficient and effective Protein design

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Synthetic and Systems Biotechnology 2024年第2期9卷 217-222页

作者： Jieling He Wenxu Wu Xiaowo Wang Ministry of Education Key Laboratory of bioinformatics Center for Synthetic and Systems BiologyBioinformatics DivisionBeijing National Research Center for Information Science and TechnologyDepartment of AutomationTsinghua UniversityBeijingChina

The protein inverse folding problem,designing amino acid sequences that fold into desired protein structures,is a critical challenge in biological *** numerous data-driven and knowledge-driven methods,there remains a need for a user-friendly toolkit that effectively integrates these approaches for in-silico protein *** this paper,we present DIProT,an interactive protein design *** leverages a non-autoregressive deep generative model to solve the inverse folding problem,combined with a protein structure prediction *** integration allows users to incorporate prior knowledge into the design process,evaluate designs in silico,and form a virtual design loop with human *** inverse folding model demonstrates competitive performance in terms of effectiveness and efficiency on TS50 and CATH4.2 datasets,with promising sequence recovery and inference *** studies further illustrate how DIProT can facilitate user-guided protein design.

关键词： Computational Protein design Interactive design toolkit Protein inverse folding Non-autoregressive decoding

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Single-cell Transcriptomes Reveal Characteristics of MicroRNAs in Gene Expression Noise Reduction

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Genomics, Proteomics & bioinformatics 2021年第3期19卷 394-407页

作者： Tao Hu Lei Wei Shuailin Li Tianrun Cheng Xuegong Zhang Xiaowo Wang Ministry of Education Key Laboratory of bioinformatics Center for Synthetic and Systems BiologyBioinformatics DivisionBeijing National Research Center for Information Science and TechnologyDepartment of AutomationTsinghua UniversityBeijing 100084China

Isogenic cells growing in identical environments show cell-to-cell variations because of the stochasticity in gene *** levels of variation or noise can disrupt robust gene expression and result in tremendous consequences for cell *** this work,we showed evidence from single-cell RNA sequencing data analysis that microRNAs(miRNAs)can reduce gene expression noise at the mRNA level in mouse *** identified that the miRNA expression level,number of targets,target pool abundance,and miRNA-target interaction strength are the key features contributing to noise *** tend to work together in cooperative subnetworks to repress target noise synergistically in a cell type-specific *** building a physical model of post-transcriptional regulation and observing in synthetic gene circuits,we demonstrated that accelerated degradation with elevated transcriptional activation of the miRNA target provides resistance to extrinsic ***,through the integrated analysis of single-cell RNA and miRNA expression profiles,we demonstrated that miRNAs are important post-transcriptional regulators for reducing gene expression noise and conferring robustness to biological processes.

关键词： MicroRNA regulation Gene expression noise Competing RNA microRNA regulation network Singlecell RNA sequencing

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Genome-Wide Analysis of Epigenetic Modifications

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Journal of Computer Science & Technology 2010年第1期25卷 35-41页

作者：梁守丹 Department of bioinformatics and Computational Biology The University of Texas M.D. Anderson Cancer Center Houston

In plants and animals, gene expression can be altered by changes that do not alter the sequence of nucleotides in DNA but rather modify the chemical structure of either the DNA or the histones that interact with the DNA. These so-called epigenetic modifications are not transient, but persist through cell divisions. Rapidly advancing technologies, such as next-generation DNA sequencing, have dramatically increased our ability to survey epigenetic markers throughout an entire genome. These techniques are revealing in great detail that the many forms and stages of cancer are characterized by a massive number of epigenetic changes. Interpreting such epigenetic marks in cell differentiation and in carcinogenesis is computationally challenging. We review several examples of epigenetic data analysis and discuss the need for computational methods that will enable us to learn from the data the relationships between different kinds of histone modifications and DNA methylation.

关键词： epigenetics non-coding DNA DNA methylations histone modifications

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ASpediaFI:Functional Interaction Analysis of Alternative Splicing Events

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Genomics, Proteomics & bioinformatics 2022年第3期20卷 466-482页

作者： Kyubin Lee Doyeong Yu Daejin Hyung Soo Young Cho Charny Park bioinformatics Branch Research InstituteNational Cancer CenterGoyang 10408Republic of Korea

Alternative splicing(AS)regulates biological processes governing phenotypes and *** AS(DAS)gene test methods have been developed to investigate important exonic expression from high-throughput ***,the DAS events extracted using statistical tests are insufficient to delineate relevant biological *** this study,we developed a novel application,Alternative Splicing Encyclopedia:Functional Interaction(ASpediaFI),to systemically identify DAS events and co-regulated genes and *** establishes a heterogeneous interaction network of genes and their feature nodes(i.e.,AS events and pathways)connected by coexpression or pathway gene set ***,ASpediaFI explores the interaction network using the random walk with restart algorithm and interrogates the proximity from a query gene ***,ASpediaFI extracts significant AS events,genes,and *** evaluate the performance of our method,we simulated RNA sequencing(RNA-seq)datasets to consider various conditions of sequencing depth and sample *** performance was compared with that of other ***,we analyzed three public datasets of cancer patients or cell lines to evaluate how well ASpediaFI detects biologically relevant *** exhibits strong performance in both simulated and public *** integrative approach reveals that DAS events that recognize a global co-expression network and relevant pathways determine the functional importance of spliced genes in the *** is publicly available at https://***/packages/ASpediaFI.

关键词： Alternative splicing RNA-seq Heterogeneous interaction network Random walk with restart Gene set enrichment analysis

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Small RNA in rice genome

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Science China(Life Sciences) 2002年第5期45卷 497-503页

作者：王凯朱小蓬钟兰陈润生 Beijing Genomics Institute/center of Genomics and bioinformatics Chinese Academy of Sciences Beijing 101300 China Beijing Genomics Institute/Center of Genomics and Bioinformatics Chinese Academy of Sciences Beijing 101300 China College of Life Sciences Peking University Beijing 100871 China Beijing Genomics Institute/Center of Genomics and Bioinformatics Chinese Academy of Sciences Beijing 101300 China Laboratory of bioinformatics Institute of Biophysics Chinese Academy of Sciences Beijing 100101 China

Rice has many characteristics of a model plant. The recent completion of the draft of the rice genome represents an important advance in our knowledge of plant biology and also has an important contribution to the understanding of general genomic evolution. Besides the rice genome finishing map, the next urgent step for rice researchers is to annotate the genes and noncoding functional sequences. The recent work shows that noncoding RNAs (ncRNAs) play significant roles in biological systems. We have explored all the known small RNAs (a kind of ncRNA) within rice genome and other six species sequences, including Arabidopsis, maize, yeast, worm, mouse and pig. As a result we find 160 out of 552 small RNAs (sRNAs) in database have homologs in 108 rice scaffolds, and almost all of them (99.41%) locate in intron regions of rice by gene predication. 19 sRNAs only appear in rice. More importantly, we find two special U14 sRNAs: one is located in a set of sRNA ZMU14SNR9(s) which only appears in three plants, 86% sequences of them can be compared as the same sequence in rice, Arabidopsis and maize; the other conserved sRNA XLHS7CU14 has a segment which appears in almost all these species from plants to animals. All these results indicate that sRNA do not have evident borderline between plants and animals.

关键词： ncRNA, sRNA, conserved sequences, plant-specific sRNA gene.

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