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Population-scale genetic control of alternative polyadenylation and its association with human diseases

Quantitative biology 2022年第1期10卷 44-54页

作者： Lei Li Yumei Li Xudong Zou Fuduan Peng Ya Cui Eric J.Wagner Wei Li Institute of systems and Physical biology Shenzhen Bay LaboratoryShenzhen 518055China Division of computational Biomedicine Department of Biological ChemistrySchool of MedicineUniversity of CaliforniaIrvineCA 92697USA Department of Biochemistry&Molecular biology University of Texas Medical BranchGalvestonTX 77555USA

Background:Genome-wide association studies(GWAS)have identified thousands of genomic non-coding variants statistically associated with many human traits and diseases,including ***,the functional interpretation of these non-coding variants remains a significant challenge in the post-GWAS *** polyadenylation(APA)plays an essential role in post-transcriptional regulation for most human *** employing different poly(A)sites,genes can either shorten or extend the 3'-UTRs that contain cu-regulatory elements such as miRNAs or RNA-binding protein binding ***,APA can affect the mRNA stability,translation,and cellular localization of ***-scale studies have revealed many inherited genetic variants that potentially impact APA to further influence disease susceptibility and phenotypic diversity,but systematic computational investigations to delineate the connections are in their earliest ***:Here,we discuss the evolving definitions of the genetic basis of APA and the modern genomics tools to identify,characterize,and validate the genetic influences of APA events in human *** also explore the emerging and surprisingly complex molecular mechanisms that regulate APA and summarize the genetic control of APA that is associated with complex human diseases and ***:APA is an intermediate molecular phenotype that can translate human common non-coding variants to individual phenotypic variability and disease susceptibility.

关键词： GWAS eQTL disease alternative polyadenylation

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Single-cell systems neuroscience:A growing frontier in mental illness

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BIOCELL 2022年第1期46卷 7-11页

作者： SEAN J.O’SULLIVAN Daniel Baugh Institute for Functional Genomics and computational biology Department of PathologyAnatomy and Cell BiologyThomas Jefferson UniversityPhiladelphiaUSA Brain Stimulation Laboratory Stanford UniversityStanfordUSA

The development of effective treatments for psychiatric disease has been disappointing in recent decades given the advancements in ***,rising rates of mental ilness such as addiction and depression compel scientists and physicians to discover novel and creative *** such approach that has proven effective is systems neuroscience:A focus on networks as opposed to ***,investigation at the single-cell and circuit level is likely to be fruitful in such endeavors as this resolution describes the functional psychopathology that allows for intervention.

关键词： systems biology systemsneuroscience Single-cellpsychiatry Psychopathology

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Bioinformatics approaches to analyzing CRISPR screen data:from dropout screens to single-cell CRISPR screens

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Quantitative biology 2022年第4期10卷 307-320页

作者： Yueshan Zhao Min Zhang Da Yang Center for Pharmacogenetics Department of Pharmaceutical SciencesUniversity of PittsburghPittsburgh PA 15261USA UPMC Hillman Cancer Institute University of PittsburghPittsburghPA 15261USA Department of computational and systems biology University of PittsburghPittsburghPA 15261USA

Background:Pooled CRISPR screen is a promising tool in drug targets or essential genes identification with the utilization of three different systems including CRISPR knockout(CRISPRko),CRISPR interference(CRISPRi)and CRISPR activation(CRISPRa).Aside from continuous improvements in technology,more and more bioinformatics methods have been developed to analyze the data obtained by CRISPR screens which facilitate better understanding of physiological ***:Here,we provide an overview on the application of CRISPR screens and bioinformatics approaches to analyzing different types of CRISPR screen *** also discuss mechanisms and underlying challenges for the analysis of dropout screens,sorting-based screens and single-cell ***:Different analysis approaches should be chosen based on the design of *** review will help community to better design novel algorithms and provide suggestions for wet-lab researchers to choose from different analysis methods.

关键词： CRISPR/Cas9 dropout screen sorting-based screen single-cell CRISPR screen drug-gene interaction

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computational Challenges in Deciphering Genomic Structures of Bacteria

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Journal of Computer Science & Technology 2010年第1期25卷 53-70页

作者：徐鹰 computational systems biology Laboratory Department of Biochemistry and Molecular Biology and Institute of Bioinformatics The University of Georgia BESC BioEnergy Science Center College of Computer Science and Technology Jilin University

This article addresses how the functionalities of the cellular machinery of a bacterium might have constrained the genomic arrangement of its genes during evolution and how we can study such problems using computational approaches, taking full advantage of the rapidly increasing pool of the sequenced bacterial genomes, potentially leading to a much improved understanding of why a bacterial genome is organized in the way it is. This article discusses a number of challenging computational problems in elucidating the genomic structures at multiple levels and the information that is encoded through these genomic structures, gearing towards the ultimate understanding of the governing rules of bacterial genome organization.

关键词： bioinformatics microbial genomics genome structure comparative genome analysis biological pathways

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A computational study for understanding the impact of p120-catenin on the cis-dimerization of cadherin

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Journal of Molecular Cell biology 2023年第9期15卷 14-24页

作者： Zhaoqian Su Vinh H.Vu Deborah ELeckband Yinghao Wu Department of systems and computational biology Albert Einstein College of Medicine1300 Morris Park AvenueBronxNY10461USA Department of Biochemistry and University of linois Urbana-ChampaignUrbanaIL 61801USA Department of Chemical and Biomolecular Engineering University of llinoisUrbana-ChampaignUrbanaIL 61801USA

A prototype of cross-membrane signal transduction is that extracellular binding of cell surface receptors to their ligands induces intracellular signalling ***,much less is known about the process in the opposite direction,called inside-out *** studies show that it plays a more important role in regulating the functions of many cell surface receptors than we used to *** particular,in cadherin-mediated cell adhesion,recent experiments indicate that intracellular binding of the scaffold protein p120-catenin(p120ctn)can promote extracellular clustering of cadherin and alter its adhesive *** underlying mechanism,however,is not well *** explore possible mechanisms,we designed a new multiscale simulation *** all-atom molecular dynamics simulations,we found that the conformational dynamics of the cadherin extracellular region can be altered by the intracellular binding of *** intriguingly,by integrating all-atom simulation results into coarse-grained random sampling,we showed that the altered conformational dynamics of cadherin caused by the binding of p120ctn can increase the probability of lateral interactions between cadherins on the cell *** results suggest that p120ctn could allosterically regulate the cis-dimerization of cadherin through two ***,p120ctn controls the extracellular conformational dynamics of ***,p120ctn oligomerization can further promote cadherin ***,our study provides a mechanistic foundation for the inside-out signalling in cadherin-mediated cell adhesion,while the computational framework can be generally applied to other cross-membrane signal transduction systems.

关键词： multiscale modeling inside-out signaling molecular dynamics simulations cadherin-mediated cell adhesion

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Neutrophil peptide 1 accelerates the clearance of degenerative axons during Wallerian degeneration by activating macrophages after peripheral nerve crush injury

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Neural Regeneration Research 2024年第8期19卷 1822-1827页

作者： Yuhui Kou Yusong Yuan Qicheng Li Wenyong Xie Hailin Xu Na Han Department of Trauma and Orthopedics Peking University People’s HospitalBeijingChina National Center for Trauma Medicine BeijingChina Key Laboratory of Trauma and Neural Regeneration(Peking University) Ministry of EducationBeijingChina Department of Orthopedics China-Japan Friendship HospitalBeijingChina Department of Central Laboratory and Institute of Clinical Molecular biology Peking University People’s HospitalBeijingChina

Macrophages play an important role in peripheral nerve regeneration,but the specific mechanism of regeneration is still *** preliminary findings indicated that neutrophil peptide 1 is an innate immune peptide closely involved in peripheral nerve ***,the mechanism by which neutrophil peptide 1 enhances nerve regeneration remains *** study was designed to investigate the relationship between neutrophil peptide 1 and macrophages in vivo and in vitro in peripheral nerve crush *** functions of RAW 264.7 cells we re elucidated by Cell Counting Kit-8 assay,flow cytometry,migration assays,phagocytosis assays,immunohistochemistry and enzyme-linked immunosorbent *** debris phagocytosis was observed using the CUBIC(Clear,Unobstructed Brain/Body Imaging Cocktails and computational analysis)optical clearing technique during Wallerian *** inflammatory factor expression in different polarization states was detected using a protein *** results showed that neutrophil peptide 1 promoted the prolife ration,migration and phagocytosis of macrophages,and CD206 expression on the surfa ce of macrophages,indicating M2 *** axonal debris clearance rate during Wallerian degeneration was enhanced after neutrophil peptide 1 *** peptide 1 also downregulated inflammatory factors interleukin-1α,-6,-12,and tumor necrosis factor-αin invo and in ***,the results suggest that neutrophil peptide 1 activates macrophages and accelerates Wallerian degeneration,which may be one mechanism by which neutrophil peptide 1 enhances peripheral nerve regeneration.

关键词： axonal debris inflammatory factors macrophages neutrophil peptide 1 peripheral nerve injury peripheral nerve regeneration RAW 264.7 cells sciatic nerve Wallerian degeneration

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Sarve:synthetic data and local differential privacy for private frequency estimation

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Cybersecurity 2022年第4期5卷 97-116页

作者： Gatha Varmal Ritu Chauhan Dhananjay Singh Amity Institute of Information Technology Amity UniversityNoidaIndia Center for computational biology and Bioinformatics Amity UniversityNoidaIndia Department of Electronics Engineering HUFSSeoulKorea

The collection of user attributes by service providers is a double-edged *** are instrumental in driving statistical analysis to train more accurate predictive models like *** analysis of the collected user data includes frequency estimation for categorical ***,the users deserve privacy guarantees against inadvertent identity *** algorithms called frequency oracles were developed to randomize or perturb user attributes and estimate the frequencies of their *** propose Sarve,a frequency oracle that used Randomized Aggregatable Privacy-Preserving Ordinal Response(RAPPOR)and Hadamard Response(HR)for randomization in combination with fake *** design of a service-oriented architecture must consider two types of complexities,namely computational and *** functions of such systems aim to minimize the two complexities and therefore,the choice of privacy-enhancing methods must be a calculated *** variant of RAPPOR we had used was realized through bloom flters.A bloom filter is a memory-efficient data structure that offers time complexity of O(1).On the other hand,HR has been proven to give the best communication costs of the order of log(b)for b-bits ***,Sarve is a step towards frequency oracles that exhibit how privacy provisions of existing methods can be combined with those of fake data to achieve statistical results comparable to the original *** also implemented an adaptive solution enhanced from the work of Arcolezi et *** use of RAPPOR was found to provide better privacy-utility tradeoffs for specific privacy budgets in both high and general privacyregimes.

关键词： Synthetic data Differential privacy Frequency estimation Frequency oracle Privacy

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Copper-catalyzed enantioselective desymmetrizing C（sp）–H functionalization of azide-ynamides via α-imino copper carbenes

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Science China Chemistry 2024年

作者： En-He Huang Li-Gao Liu You-Wei Yin Hao-Xuan Dong Ji-Jia Zhou Xin Lu Bo Zhou Long-Wu Ye Key Laboratory for Chemical biology of Fujian Province and State Key Laboratory of Physical Chemistry of Solid Surfaces College of Chemistry and Chemical Engineering Xiamen University State Key Laboratory of Organometallic Chemistry Shanghai Institute of Organic Chemistry Chinese Academy of Sciences

α-Imino metal carbenes are versatile intermediates in organic synthesis, and have broad applications in the assembly of divergent N-heterocycles. However, the catalytic enantioselective desymmetrization based on α-imino metal carbenes has not been developed to date. Herein, we disclose an enantioselective desymmetrizing C（sp2）–H functionalization of azide-ynamides via α-imino copper carbenes, leading to the efficient assembly of divergent chiral indoloazepines in generally moderate to excellent yields with high enantioselectivities. Notably, this reaction represents the first enantioselective desymmetrization based on α-imino metal carbenes. Further synthetic transformations and biological tests show the potential utility of this method. Moreover,computational studies are employed to elucidate the reaction mechanism and the origin of enantioselectivity.

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The next generation models for crops and agro-ecosystems

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Science China(Information Sciences) 2011年第3期54卷 589-597页

作者： THOLEN Danny Plant systems biology Group CAS-MPG Partner Institute and Key Laboratory for Computational BiologyShanghai Institutes for Biological SciencesChinese Academy of Sciences

Growth in population, decrease in arable land area, and change in climate are endangering our food security. Precision agriculture has the potential to increase crop productivity thorough tailored agricultural practices for different growing areas. Many models of crops and agro-ecosystems capable of predicting interaction between plants and environments have been developed for precision agriculture. Currently, there are several representative categories of crop and agro-ecosystem models, including the de Wit school models, the DSSAT series models and the APSIM series models, which have contributed substantially to improvement of agricultural practices. However, these models are weak in predicting performances of crops under environmental and genetic perturbations are generally weak, which severely limits the application of these models in guiding precision agriculture. We need to develop the next generation crop and agro-ecosystems models with a high level of mechanistic basis, which can be integrated with high throughput data and can predict the heterogeneity of environmental factors inside canopy and dynamic canopy photosynthesis. In developing such a model close collaboration is inevitably required among scientists from different disciplines. The successful development and application of such models will undoubtedly advance precision agriculture through providing better agronomical practices tailored for different growing environments. These models will also form a basis to identify breeding targets for increased productivity at given location with given soil and climatic conditions.

关键词： crop models ecosystem models crop yields nonlinear analysis photosynthesis

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Impacts of environmental conditions on woody plant diversity,structure and regeneration in forest patches of Guna Mountain:Este District,South Gondar Zone,Ethiopia

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Journal of Mountain Science 2023年第7期20卷 1940-1953页

作者： DILNESSA Gashaye ZERIHUN Woldu SILESHI Nemomissa ENYEW Adgo Department of Plant biology and Biodiversity Management Addis Ababa UniversityAddis Ababa 1000Ethiopia Department of biology Natural and Computational Sciences FacultyDebre Tabor UniversityDebre Tabor 6300Ethiopia Department of Soil Sciences Bahir Dar UniversityBahir Dar 6000Ethiopia

Environmental conditions determine woody plant life such as species diversity,structure and regeneration *** research aimed to assess the impact of environmental conditions on woody plant species diversity,structure and regeneration in forest patches of Guna Mountain:the case of Este District,South Gondar Zone,north-west Ethiopia.A total of 71 square sample plots(400 m~2 each) were established at 10 transects laid in five forest patches of the study area to collect vegetation data including the abundance of species,height and diameter at breast height(DBH).Environmental data including available potassium,available phosphorus,cation exchange capacity,soil texture,electrical conductivity,soil acidity,total nitrogen,organic matter,organic carbon,sodium adsorption ratio,exchangeable sodium percentage,bulk density,aspect,elevation,slope,latitude and longitude data were collected in the same plots.A correlation analysis between vegetation and environmental data was performed using rcorr(x) function in package Hmisc in R Programming *** most pronounced impacts were observed in altitude,grazing and pH,positively and silt,sand,electrical conductivity and cation exchange capacity,*** addition,strong and significant impacts on plant structure were also observed due to the variation in soil texture and p *** difference in aspect,sand and slope also impacted plant *** study showed that environmental parameters influence the diversity,structure and regeneration of woody *** parameters can be considered in the rehabilitation of the vegetation cover and conservation efforts of the rare woody *** measures that can minimalize the negative influences of environmental conditions can be applied through collaboration with communities around the forest patches.

关键词： Altitude Human disturbance Environmental condition Plant diversity Plant structure Vegetation

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