Trajectory analysis

轨迹分析
  • 文章类型: Journal Article
    糖尿病肾病(DKD)是终末期肾病(ESRD)的主要原因,其发病机制尚未明确。目前的研究表明,DKD涉及多种细胞类型和肾外因素,阐明发病机制和确定新的治疗靶点尤为重要。单细胞RNA测序(scRNA-seq)技术是在单细胞水平上对单个细胞的转录组进行高通量测序,这是一种通过比较遗传信息来探索疾病发展的有效技术,反映了细胞之间遗传信息的差异,识别不同的细胞亚群。越来越多的证据支持scRNA-seq在揭示糖尿病发病机制和加强我们对DKD分子机制的理解中的作用。这次我们回顾了scRNA-seq数据。然后,我们分析和讨论了scRNA-seq技术在DKD研究中的应用,包括细胞类型的注释,新细胞类型(或亚型)的鉴定,细胞间通讯的识别,细胞分化轨迹分析,基因表达检测,和分析基因调控网络,最后,我们探讨了scRNA-seq技术在DKD研究中的未来前景。
    Diabetic kidney disease (DKD) is the leading cause of end-stage renal disease (ESRD), and its pathogenesis has not been clarified. Current research suggests that DKD involves multiple cell types and extra-renal factors, and it is particularly important to clarify the pathogenesis and identify new therapeutic targets. Single-cell RNA sequencing (scRNA-seq) technology is high-throughput sequencing of the transcriptomes of individual cells at the single-cell level, which is an effective technology for exploring the development of diseases by comparing genetic information, reflecting the differences in genetic information between cells, and identifying different cell subpopulations. Accumulating evidence supports the role of scRNA-seq in revealing the pathogenesis of diabetes and strengthening our understanding of the molecular mechanisms of DKD. We reviewed the scRNA-seq data this time. Then, we analyzed and discussed the applications of scRNA-seq technology in DKD research, including annotation of cell types, identification of novel cell types (or subtypes), identification of intercellular communication, analysis of cell differentiation trajectories, gene expression detection, and analysis of gene regulatory networks, and lastly, we explored the future perspectives of scRNA-seq technology in DKD research.
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  • 文章类型: Journal Article
    阿尔茨海默病(AD)是最常见的痴呆,以进行性认知障碍和神经变性为特征。广泛的临床和基因组研究揭示了生物标志物,危险因素,通路,以及过去十年AD的目标。然而,AD发生和进展的确切分子基础仍然难以捉摸。新兴的单细胞测序技术可以潜在地提供对疾病的细胞水平见解。在这里,我们系统地回顾了最先进的生物信息学方法来分析单细胞测序数据及其在14个主要方向上的应用。包括1)质量控制和标准化,2)降维和特征提取,3)细胞聚类分析,4)细胞类型的推断和注释,5)差异表达,6)轨迹推断,7)拷贝数变异分析,8)整合单细胞多组学,9)表观基因组分析,10)基因网络推断,11)细胞亚群的优先排序,12)人和小鼠sc-RNA-seq数据的整合分析,13)空间转录组学,和14)比较单细胞AD小鼠模型研究和单细胞人AD研究。我们还解决了使用人类死后和小鼠组织的挑战,并概述了单细胞测序数据分析的未来发展。重要的是,我们已经为每个主要分析方向实施了推荐的工作流程,并将其应用于AD中的大型单核RNA测序(snRNA-seq)数据集.报告关键分析结果,同时通过GitHub与研究社区共享脚本和数据。总之,这篇全面的综述提供了分析单细胞测序数据的各种方法的见解,并为研究设计和各种分析方向提供了具体指南。审查和伴随的软件工具将作为研究AD的细胞和分子机制的宝贵资源,其他疾病,或单细胞水平的生物系统。
    Alzheimer\'s disease (AD) is the most common form of dementia, characterized by progressive cognitive impairment and neurodegeneration. Extensive clinical and genomic studies have revealed biomarkers, risk factors, pathways, and targets of AD in the past decade. However, the exact molecular basis of AD development and progression remains elusive. The emerging single-cell sequencing technology can potentially provide cell-level insights into the disease. Here we systematically review the state-of-the-art bioinformatics approaches to analyze single-cell sequencing data and their applications to AD in 14 major directions, including 1) quality control and normalization, 2) dimension reduction and feature extraction, 3) cell clustering analysis, 4) cell type inference and annotation, 5) differential expression, 6) trajectory inference, 7) copy number variation analysis, 8) integration of single-cell multi-omics, 9) epigenomic analysis, 10) gene network inference, 11) prioritization of cell subpopulations, 12) integrative analysis of human and mouse sc-RNA-seq data, 13) spatial transcriptomics, and 14) comparison of single cell AD mouse model studies and single cell human AD studies. We also address challenges in using human postmortem and mouse tissues and outline future developments in single cell sequencing data analysis. Importantly, we have implemented our recommended workflow for each major analytic direction and applied them to a large single nucleus RNA-sequencing (snRNA-seq) dataset in AD. Key analytic results are reported while the scripts and the data are shared with the research community through  GitHub. In summary, this comprehensive review provides insights into various approaches to analyze single cell sequencing data and offers specific guidelines for study design and a variety of analytic directions. The review and the accompanied software tools will serve as a valuable resource for studying cellular and molecular mechanisms of AD, other diseases, or biological systems at the single cell level.
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  • 文章类型: Journal Article
    OBJECTIVE: To examine the hypothesis that PTSD with delayed expression in some cases occurs without subthreshold PTSD symptoms above background levels bridging the gap between the traumatic exposure(s) and the clinical diagnosis.
    METHODS: We performed systematic searches of peer-reviewed papers in English referenced in Pubmed, Embase, or PsycINFO and ascertained 34 prospective studies of PTSD symptom trajectories identified by latent class growth statistical modeling. Studies with delayed and low-stable trajectories provided appropriate data for this study. We computed the difference between the delayed trajectory PTSD symptom sumscore and the low-stable PTSD sumscore at the observed points in time after the traumatic event(s).
    RESULTS: In 29 study populations, the latent class growth analyses displayed delayed trajectories, and in these, we identified 110 data points (% PTSD sumscore difference/months since traumatic exposure). The median PTSD symptom sumscore was 25% higher during the initial 6 months among individuals in the delayed trajectory compared to those in low-stable trajectory. From this level, the difference widened and reached a plateau of 40-50% higher. The variation was large, and the baseline participation rate and loss to follow-up were exceeding 25% in the majority of the studies. Heterogeneity of populations, measures, and analyses precluded formal meta-analysis.
    CONCLUSIONS: Delayed PTSD is preceded by PTSD symptoms during the first year in most cases. Still, few individuals may experience an asymptomatic delay. The results underpin the rationale for monitoring PTSD symptoms and may inform forensic assessments in that delayed PTSD without symptoms bridging the traumatic event is rare.
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  • 文章类型: Journal Article
    轨迹分析根据香烟使用的早期模式来区分吸烟者的亚组,但是没有研究总结这些文献。我们系统地回顾了有关青少年吸烟轨迹的文献,以记录已识别的轨迹的数量和形状,评估某些研究特征是否影响已识别轨迹的数量或形状,总结与轨迹组成员身份相关的因素和结果,并评估轨迹分析的结果是否有助于识别干预的机会窗口。我们搜索了PubMed和EMBASE(1980年1月1日至2018年1月11日),并确定了1695篇文章。保留了来自37个独特数据集的43篇文章。每个轨迹被分为三组中的一组(即,低稳定,增加,其他)。轨迹的数量范围从2到6(模式=4);44-76%的参与者是低稳定的香烟消费者,消费增加11-21%,3-11%被归类为“其他”。\"数据点的数量,使用的吸烟指示器,和时间轴影响识别的轨迹的数量。只有两篇文章描述了自发病以来吸烟的自然过程。与轨迹成员资格相关的因素包括年龄,性别/性别,种族/民族,父母教育,行为问题,抑郁症,学业成绩,基线香烟使用,父母和朋友吸烟,酒精使用,使用大麻。结果包括非法药物和酒精使用。除了吝啬地描述吸烟模式,目前尚不清楚轨迹分析是否可以提高对自然过程的洞察力,吸烟的决定因素或结果,以告知干预措施的发展。
    Trajectory analyses differentiate subgroups of smokers based on early patterns of cigarette use, but no study has summarized this literature. We systematically reviewed the literature on adolescent cigarette smoking trajectories to document the number and shapes of trajectories identified, assess if certain study characteristics influence the number or shapes of trajectories identified, summarize factors associated with and outcomes of trajectory group membership, and assess whether the results of trajectory analyses help identify windows of opportunity for intervention. We searched PubMed and EMBASE (1/1/1980 to 1/11/2018) and identified 1695 articles. Forty-three articles with data from 37 unique datasets were retained. Each trajectory was categorized into one of three groups (i.e., low-stable, increasing, other). Number of trajectories ranged from 2 to 6 (mode = 4); 44-76% of participants were low-stable cigarette consumers, 11-21% increased consumption, and 3-11% were categorized as \"other.\" Number of data points, smoking indicator used, and time axis influenced the number of trajectories identified. Only two articles depicted the natural course of smoking since onset. Factors associated with trajectory membership included age, sex/gender, race/ethnicity, parental education, behavior problems, depression, academic performance, baseline cigarette use, parental and friends smoking, alcohol use, and cannabis use. Outcomes included illicit drug and alcohol use. Beyond parsimoniously describing cigarette smoking patterns, it is not clear whether trajectory analyses offer increased insight into the natural course, determinants or outcomes of cigarette smoking in ways that inform the development of intervention.
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  • 文章类型: Journal Article
    在药物依从性文献中使用基于组的轨迹(GBTM)建模正在迅速增长。研究人员正在采用增强的方法来分析和可视化动态行为,如药物依从性,在“现实世界”人群中。基于纵向粘附行为的GBTM的应用允许识别粘附轨迹或组。从概念上讲,一个组是指在一段时间内遵循类似遵守行为模式的个人集合。研究人员在实施GBTM时面临的一个常见障碍是决定人群中可能存在的轨迹组的数量。决策可以引入主观性,因为型号选择标准没有“黄金标准”。本研究旨在检查GBTM用于药物依从性评估的现有证据的程度和性质。概述了文献中使用的不同GBTM技术。方法论框架将包括五个阶段:i)确定研究问题;ii)确定相关研究;iii)选择研究;iv)绘制数据图,最后,v)整理,总结并报告结果。同行评审的原创文章,以英文出版,描述观察性研究,包括GBTM和药物依从性的概念和/或子概念或任何其他类似术语,将包括在内。将查询以下数据库:PubMed/MEDLINE;Embase(Ovid);SCOPUS;ISIWebofScienceandPsychInfo。此范围审查将利用PRISMA扩展范围审查(PRISMA-ScR)工具来报告结果。本范围审查将收集并概述迄今为止文献中可用的GBTM应用于药物依从性评估的不同技术,确定这一领域的研究和知识差距。这篇综述可以代表未来研究的重要工具,为进行基于小组的轨迹分析的研究人员提供方法学支持,以在现实世界中评估药物依从性。
    The use of group-based trajectory modelling (GBTM) within the medication adherence literature is rapidly growing. Researchers are adopting enhanced methods to analyse and visualise dynamic behaviours, such as medication adherence, within \'real-world\' populations. Application of GBTM based on longitudinal adherence behaviour allows for the identification of adherence trajectories or groups.  A group is conceptually thought of a collection of individuals who follow a similar pattern of adherence behaviour over a period of time. A common obstacle faced by researchers when implementing GBTM is deciding on the number of trajectory groups that may exist within a population. Decision-making can introduce subjectivity, as there is no \'gold standard\' for model selection criteria. This study aims to examine the extent and nature of existing evidence on the application of GBTM for medication adherence assessment, providing an overview of the different GBTM techniques used in the literature. The methodological framework will consist of five stages: i) identify the research question(s); ii) identify relevant studies; iii) select studies; iv) chart the data and finally, v) collate, summarise and report the results. Original peer-reviewed articles, published in English, describing observational and interventional studies including both concepts and/or sub-concepts of GBTM and medication adherence or any other similar terms, will be included. The following databases will be queried: PubMed/MEDLINE; Embase (Ovid); SCOPUS; ISI Web of Science and PsychInfo. This scoping review will utilise the PRISMA extension for Scoping Reviews (PRISMA-ScR) tool to report results. This scoping review will collect and schematise different techniques in the application of GBTM for medication adherence assessment available in the literature to date, identifying research and knowledge gaps in this area. This review can represent an important tool for future research, providing methodological support to researchers carrying out a group-based trajectory analysis to assess medication adherence in a real-world context.
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