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多模态组学数据整合方法的性能评测

基因组学与应用生物学 2024年第7期43卷 1196-1213页

作者：杨品任振华袁增强安徽医科大学基础医学院合肥230032 北京基础医学研究所脑科学中心北京100850

多模态组学数据的联合运用在揭示细胞异质性和解析细胞命运调控机制方面具有重要意义,目前已有多种方法被开发,用于处理不同组学模态数据的整合。本研究通过对应用于不同整合任务的多种数据整合方法进行性能评测,为相关领域的研究提供... 详细信息

多模态组学数据的联合运用在揭示细胞异质性和解析细胞命运调控机制方面具有重要意义,目前已有多种方法被开发,用于处理不同组学模态数据的整合。本研究通过对应用于不同整合任务的多种数据整合方法进行性能评测,为相关领域的研究提供有益参考。使用6个联合测序数据集对16种单细胞多模态配对数据整合方法在2类整合任务上的性能进行测试,再通过4个模拟数据集和1个真实数据集对6种空间转录组反卷积方法的性能进行评估。在RNA和ATAC配对数据整合任务中,MOFA+、 SCOIT、 Cobolt分别在PBMC、 BMMC、 SNARE数据集上取得最优表现,SCOIT在3个数据集的汇总得分中均排名前3, MMDVAE、 DAE在基于AE的融合算法中表现突出。在RNA和蛋白质配对数据整合任务中,Cobolt、 MOFA+、 Seurat分别在P5_CITE、 BM_CITE、 COVID中取得最优表现,totalVI在3个数据集的汇总得分中排名靠前,基于AE的融合算法中以efMMDVAE、 lfMMDVAE的表现最好。在空间转录组反卷积方法评测中,Cell2location和SPACEL在模拟数据和真实数据中的性能表现均优于其他方法的,其中Cell2location在真实数据集中表现最佳,正确地推断了两类心肌细胞在心室的比例。此外,本研究发现在配对数据整合任务中,不同方法对数据的适应性不同。SCOIT和totalVI分别是RNA与ATAC、 RNA与蛋白质数据整合中表现稳定优异的方法。Seurat、 MOFA+易受数据影响。

关键词：单细胞组学空间转录组学多模态组学联合测序数据整合

Redemystifying MST1/hippo signaling

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Protein & Cell 2010年第8期1卷 706-708页

作者： Lei Xiao zengqiang yuan State Key Laboratory of Brain and Cognitive Science Institute of BiophysicsChinese Academy of SciencesBeijing 100101China

Since the Mammalian Ste20-like kinases(MST)1/2 were first indentified in 1995,our knowledge about MST1/2 and its Drosophila ortholog Hippo has expanded to diverse biologic process ranging from cell survival and death,organ size control,to proliferation and ***1(also known as Stk4 and Krs2)and MST2(also known as Stk3 and Krs1)were first identified as homologs of the ste20 kinase from Saccharomyces cerevisiae(Creasy and Chernoff,1995).Subsequently,these proteins were also identified in‘in gel’kinase assays as kinases that respond to extreme cellular stress(Taylor et al.,1996).Though a number of apoptotic or stress stimuli have been reported to activate MST,proteolytic cleavage of MST by caspase 3 remains the only and best understood mechanism that regulate MST kinase activity to date(Kakeya et al.,1998).Upon proapoptotic stimuli,the N-terminal proteolytic fragment of MST translocates into the nucleus and phosphorylates histone H2B,which leads to the chromatin condensation and mammalian cell death(Cheung et al.,2003).Interestingly,histone H2B phosphorylation also occurs in ***,through the phosphorylation on Ser10,a residue distinct from mammalian histone H2B Ser14(Ahn et al.,2005).However,growing evidence suggests that full length MST also promotes cell death independently of proteolysis or nuclear translocation(Ahn et al.,2005;Lehtinen et al.,2006).In primary mammalian neurons,oxidative stress-activated-MST phosphorylates the transcription factor FOXO,which could translocate into the nucleus and upregulate the transcriptional activity of pro-death genes,including ***,the characterization of the *** ortholog CST-1 broadens MST functions beyond the control of cell death to the regulation of life span in nematodes(Lehtinen et al.,2006).Despite the flurry of interest in the MST,both the upstream regulators and downstream targets of MST in different scenarios are still in a puzzle.

关键词： expanded spite extreme

Re-mention of an old neurodegenerative disease:Alzheimer's disease

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Chinese Science Bulletin 2013年第15期58卷 1731-1736页

作者： ZHANG Peng ADAMS Ursula yuan zengqiang State Key Laboratory of Brain and Cognitive Sciences Institute of BiophysicsChinese Academy of Sciences Biological Sciences The University of Chicago

Alzheimer's disease(AD),the most common form of neuropsychiatric disorder,is characterized by neuronal degeneration and inexorably progressing dementia,especially in the elderly *** a rapidly aging population in both developed and developing countries,AD has emerged as one of the largest growing problems *** drugs improve the symptoms of AD,but do not have any profound intervention to delay its ***,understanding the molecular mechanisms underlying the genes tied to AD will be crucial to the development of therapeutic *** review will summarize the aetiology,pathology,and the evidence for the genetic components in AD,discuss the proposed amyloid cascade and the following tau hyperphosphorylation hypothesises,oxidative stress mediated neuronal cell death,as well as the function of Retromer complex during the developing of *** laboratory's current research progress and the challenges that still remained will be also highlighted.

关键词：神经退行性疾病阿尔茨海默氏症阿尔茨海默氏病 Complex 老年痴呆症神经细胞死亡淀粉样蛋白精神障碍

ON THE ROBUSTNESS OF A GENERALIZED PREDICTIVE CONTROLLER

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Applied Mathematics(A Journal of Chinese Universities) 1995年第4期10卷 449-456页

作者： CHEN zengqiang AND yuan ZHUZHI Department of Computer and System Sciences NanKai University Tianjin

In this paper, we present a quantitative analysis of the robustness of a generalized predictive controller. The result of stability analysis shows that, under a specific bounded modelling error, the closed-loop system... 详细信息

关键词： Robust control generalized predictive control state-space robustness stability.

Yes相关蛋白在电离辐射后表皮干细胞分化中的作用

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中国药理学与毒理学杂志 2024年第7期38卷 511-516页

作者：王丽彬陈俊飞袁方王景泽刘鹿王学武袁增强南华大学衡阳医学院军事医学研究院研究生协作培养基地湖南衡阳421001 军事医学研究院北京100850 黄山市黄山区人民医院安徽黄山245700 中国人民解放军总医院第五医学中心北京100039 兰陵县结核病防治所山东临沂277700 青岛大学基础医学院山东青岛266071

目的探讨Yes相关蛋白(YAP)在电离辐射(IR)后表皮干细胞(EPSC)分化中的作用。方法①利用打孔器建立小鼠背部皮肤损伤,随后分为IR组(给予^(60)Coγ射线局部照射),对照组(不照射);照射后0,1,3,6,9和12 d收集创面皮肤组织提取RNA和蛋白,West... 详细信息

目的探讨Yes相关蛋白(YAP)在电离辐射(IR)后表皮干细胞(EPSC)分化中的作用。方法①利用打孔器建立小鼠背部皮肤损伤,随后分为IR组(给予^(60)Coγ射线局部照射),对照组(不照射);照射后0,1,3,6,9和12 d收集创面皮肤组织提取RNA和蛋白,Western印迹法检测创面愈合过程中YAP蛋白变化;实时荧光定量PCR(RT-qPCR)检测创面愈合过程中Yap及其下游靶基因结缔组织生长因子(Ctgf)和富含半胱氨酸蛋白61(Cyr61)的mRNA变化。②将EPSC给予60Coγ射线照射,细胞对照组不照射;4或8 Gy剂量照射后4,12,24和36 h收集细胞提取RNA,RT-qPCR检测YAP mRNA变化。4或8 Gy剂量照射36 h收集细胞提取蛋白,Western印迹法检测YAP蛋白水平;③短发夹RNA(shRNA)构建稳定的YAP基因敲低细胞,Western印迹法验证shYAP的敲低效率;RT-qPCR检测IR后YAP敲低对K1和K10 mRNA的影响。结果①与对照组相比,IR组小鼠在创面愈合过程中YAP蛋白水平显著降低(P<0.05,P<0.01),Yap及其下游靶基因Ctgf和Cyr61的mRNA水平显著降低(P<0.05,P<0.01)。②与细胞对照组相比,IR组细胞YAP mRNA和蛋白水平显著降低(P<0.01)。③在shYAP稳转细胞中,YAP蛋白水平显著降低(P<0.01);shYAP在IR后EPSC分化标志物K1和K10的mRNA水平明显降低(P<0.01)。结论YAP调控IR后创面愈合过程中EPSC的分化。

关键词： Yes相关蛋白电离辐射表皮干细胞细胞分化

Pinning weighted complex networks with heterogeneous delays by a small number of feedback controllers

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Science in China(Series F) 2008年第5期51卷 511-523页

作者： XIANG LinYing LIU ZhongXin CHEN zengqiang yuan ZhuZhi Department of Automation Nankai University Tianjin 300071 China

Weighted complex dynamical networks with heterogeneous delays in both continuous-time and discrete-time domains are controlled by applying local feedback injections to a small fraction of network nodes. Some generic stability criteria ensuring delay-independent stability are derived for such controlled networks in terms of linear matrix inequalities （LMIs）, which guarantee that by placing a small number of feedback controllers on some nodes the whole network can be pinned to some desired homogenous states. In some particular cases, a single controller can achieve the control objective. It is found that stabilization of such pinned networks is completely determined by the dynamics of the individual uncoupled node, the overall coupling strength, the inner-coupling matrix, and the smallest eigenvalue of the coupling and control matrix. Numerical simulations of a weighted network composing of a 3-dimensional nonlinear system are finally given for illustration and verification.

关键词： complex dynamical network linear matrix inequality (LMI) weighted network pinning control hetero-geneous delay

Astrocytes in depression and Alzheimer’s disease

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Frontiers of Medicine 2021年第6期15卷 829-841页

作者： Yang Liao Qu Xing Qianqian Li Jing Zhang Ruiyuan Pan zengqiang yuan The Brain Science Center Beijing Institute of Basic Medical SciencesBeijing 100850China School of Life Sciences Zhengzhou UniversityZhengzhou 450001China School of Traditional Chinese Medicine Beijing University of Chinese MedicineBeijing 100029China

Astrocytes are an abundant subgroup of cells in the central nervous system(CNS)that play a critical role in controlling neuronal circuits involved in emotion,learning,and *** clinical cases,multiple chronic brain diseases may cause psychosocial and cognitive impairment,such as depression and Alzheimer’s disease(AD).For years,complex pathological conditions driven by depression and AD have been widely perceived to contribute to a high risk of disability,resulting in gradual loss of self-care ability,lower life qualities,and vast burden on human ***,correlational research on depression and AD has shown that depression might be a prodrome of progressive degenerative neurological *** a kind of multifunctional glial cell in the CNS,astrocytes maintain physiological function via supporting neuronal cells,modulating pathologic niche,and regulating energy *** evidence has shown that astrocytic dysfunction is involved in the progression of depression and *** herein review the current findings on the roles and mechanisms of astrocytes in the development of depression and AD,with an implication of potential therapeutic avenue for these diseases by targeting astrocytes.

关键词： astrocytes depression Alzheimer’s disease roles mechanisms

Mitochondrial calcium uniporter protein MCU is involved in oxidative stress-induced cell death

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Protein & Cell 2015年第6期6卷 434-442页

作者： Yajin Liao Yumin Hao Hong Chen Qing He zengqiang yuan Jinbo Cheng State Key Laboratory of Brain and Cognitive Sciences Institute of Biophysics Chinese Academy of Sciences Beijing 100101 China College of Life Sciences University of Chinese Academy of Sciences Beijing 100049 China

Mitochondrial calcium uniporter （MCU） is a conserved Ca2＋ transporter at mitochondrial in eukaryotic cells. However, the role of MCU protein in oxidative stress- induced cell death remains unclear. Here, we showed that ectopically expressed MCU is mitochondrial local- ized in both HeLa and primary cerebellar granule neu- rons （CGNs）. Knockdown of endogenous MCU decreases mitochondrial Ca2＋ uptake following his- tamine stimulation and attenuates cell death induced by oxidative stress in both HeLa cells and CGNs. We also found MCU interacts with VDACl and mediates VDAC1 overexpression-induced cell death in CGNs. This finding demonstrates that MCU-VDACl complex regulates mi- tochondrial Ca2＋ uptake and oxidative stress-induced apoptosis, which might represent therapeutic targets for oxidative stress related diseases.

关键词： MCU VDAC1 oxidative stress calciumuptake cell death

Generation of Calhm1 knockout mouse and characterization of calhm1 gene expression

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Protein & Cell 2012年第6期3卷 470-480页

作者： Junbing Wu Shengyi Peng Rong Wu Yumin Hao Guangju Ji zengqiang yuan State Key Laboratory of Brain and Cognitive Sciences Institute of BiophysicsChinese Academy of SciencesBeijing 100101China College of Life Sciences Graduate School of Chinese Academy of SciencesBeijing 100049China􀀍

Alzheimer’s disease(AD)is the most common neurode-generative disease among elderly people *** genes have been validated to be associated with AD,and calcium homeostasis modulator 1(Calhm1)is the latest suspected *** investigate the biological and pathological function of Calhm1 systematically,we generated a Calhm1 conventional knockout ***,both the male and female of elderly Calhm1 knockout(KO)mice showed similar ability to their wild type littermates in spatial learning and memory ***,we found that Calhm1 mRNA could not be detected in mouse brains at different ages,although it is expressed in the human brain *** further found that CpG islands(CGIs)of both mouse and human Calhm1 were hypermethylated,whereas CGI of mouse Calhm2 was *** addition,transcriptional active marker H3K4Di occupied on promoters of human Calhm1 and mouse Calhm2 at a considerable level in brain tissues,while the occupancy of H3K4Di on pro-moter of mouse Calhm1 was *** sum,we found that mouse Calhm1 was of rare abundance in brain *** it might not be suitable to utilize the knockout murine model to explore biological function of Calhm1 in the pathogenesis of AD.

关键词： Alzheimer’s disease calcium homeostasis modulator methylation transcription