SPACE: a web server for linking chromatin accessibility with clinical phenotypes and the immune microenvironment in pan-cancer analysis
SPACE: a web server for linking chromatin accessibility with clinical phenotypes and the immune microenvironment in pan-cancer analysis
复制标题
SPACE：一个网络服务器，用于将染色质可及性与泛癌分析中的临床表型和免疫微环境联系起来
DOI：
10.1038/s41423-020-0416-9
复制
发表时间：
2020
影响因子：
24.1
通讯作者：
Fan Yihui
中科院分区：
文献类型：
--
作者：
Wu Yingcheng;Zhao Jingwei;Zhu Haoliang;Fan Zhiwei;Yuan Xinpei;Chen Shiyin;Mao Renfang;Fan Yihui
非编码的“垃圾DNA”占我们基因组的98%，现在普遍认为它在精确调节编码基因以建立细胞身份方面起着重要作用。功能性“垃圾DNA”的一个特点是它的可获取性。在癌细胞中，异常的染色质可及性被认为是主要标志之一。了解这些事件需要高通量筛选，例如利用测序进行转座酶可及染色质分析（ATAC-seq），这产生了令生物学家困惑的大规模数据。然而，现有的网络工具只支持细胞系数据，缺乏高质量的临床表型或匹配的转录组。在这里，我们开发了Shiny Pan-cancer Accessible Chromatin Explorer (SPACE)，作为一个集所有功能于一体的web服务器，包含23种癌症类型的404例患者的562,709个调控元件。据我们所知，SPACE是第一个支持ATAC-seq分析的web应用程序，具有匹配的临床表型和转录组数据。当前版本的SPACE支持以下功能：(i)搜索排序的调控元素（峰值）；（ii）探索峰的潜在调节器；（iii）检查选定峰值的临床相关性；（iv）峰相关路径的预测；(v)峰与rna的相关性；（六）探讨峰在免疫相关肿瘤微环境中的作用。因此，对于癌症生物学家来说，SPACE是一种可操作且节省时间的表观遗传资源，可用于检查DNA调控元件的转录和表型后果。SPACE的网址是http://fun-science。俱乐部/空间。在癌细胞中，动态DNA可及性协调了一个精确的调控网络，以促进癌症中的癌基因。最先进的高通量技术，如ATAC-seq，可以为理解染色质状态如何操纵肿瘤发生提供精确的图谱，这使ATAC-seq成为表观遗传学界的焦点。然而，现有的在线工具，如Cistrome 2或ENCODE， 3对基于细胞系的分析很有用，但在临床基于样本的分析中却很少。因此，迫切需要开发具有高质量表型或匹配转录组的用户友好的调控元件资源。最近，新发表的TCGA样本的ATAC-seq数据集使探索染色质可及性的临床价值成为可能。1然而，ATAC-seq产生的大规模数据对于生物学家来说很难直接分析。将表观基因组与匹配的转录和临床信息联系起来需要编程技能和IT基础设施。在这里，我们开发了SPACE （http://fun-science）。club/SPACE)作为一个一体化的web服务器，使癌症生物学家能够分析和可视化来自23种癌症类型的404名患者的562,709个可访问的DNA元素。通过整合来自公共领域（如TCGA和ENCODE）的可用数据集，SPACE允许用户搜索峰（通过基因或基因组区域）并进一步注释峰（超级增强子、转录因子（TF）结合、顺调控、表达数量性状位点（eQTL）和文献）。通过匹配的转录组数据，SPACE记录了17,638,113,605对峰值mrna /lncRNA/miRNA及其表型关联，如预后或癌症亚型。用户还可以预测峰值相关途径及其在免疫微环境中的作用。SPACE可以作为一个有用的资源来探索DNA调控元件的作用及其相关的转录变化以及癌症患者的临床相关性。SPACE的用户界面是用R Shiny编写的。的详细程序。
Noncoding “junk DNA”, which constitutes 98% of our genome, is now generally considered to play a fundamental role in the precise regulation of coding genes to establish cell identity. One feature of functional “junk DNA” is its accessibility. In cancer cells, aberrant chromatin accessibility is recognized as one of the major hallmarks. Understanding such events requires high-throughput screening, such as Assay for Transposase-Accessible Chromatin using sequencing (ATAC-seq), which generates large-scale data that are puzzling for biologists. However, existing web tools only support cell line data and lack high-quality clinical phenotypes or matched transcriptomes. Here, we developed Shiny Pan-cancer Accessible Chromatin Explorer (SPACE) as an all-in-one web server encompassing 562,709 regulatory elements in 404 patients across 23 cancer types. To the best of our knowledge, SPACE is the first web application supporting ATAC-seq analysis with matched clinical phenotype and transcriptome data. The current version of SPACE supports the following:(i) searching of ranked regulatory elements (peaks);(ii) exploration of potential regulators of peaks;(iii) examination of the clinical relevance of selected peaks;(iv) prediction of peak-related pathways;(v) correlations of peaks with RNAs; and (vi) exploration of the role of peaks in the immunerelated tumor microenvironment. Thus, SPACE is an operable and time-saving epigenetic resource for cancer biologists to examine the transcriptional and phenotypic consequences of DNA regulatory elements. SPACE is available at http://fun-science. club/SPACE. In cancer cells, dynamic DNA accessibility orchestrates a precise regulatory network to foster oncogenes in cancer. State-of-the-art high-throughput technologies, such as ATAC-seq, can provide a precise map for understanding how chromatin states manipulate oncogenesis, which places ATAC-seq right in the limelight of the epigenetics community. 1 However, existing online tools, such as Cistrome 2 or ENCODE, 3 are useful for cell-line-based analysis but do little in clinical sample-based analysis. Thus, there is a pressing need for developing a user-friendly resource of regulatory elements with high-quality phenotypes or matched transcriptomes. Most recently, newly published ATAC-seq datasets of TCGA samples make it possible to explore the clinical value of chromatin accessibility. 1 However, large-scale data generated by ATAC-seq are hard for biologists to directly analyze. Linking the epigenome to matched transcriptional and clinical information requires programming skills and IT infrastructure. Here, we developed SPACE (http://fun-science. club/SPACE) as an all-in-one web server to enable cancer biologists to analyze and visualize 562,709 accessible DNA elements from 404 patients across 23 cancer types. By integrating available datasets from public domains such as TCGA and ENCODE, SPACE allows users to search peaks (by gene or genomic regions) and further annotate peaks (super-enhancer, transcription factor (TF) binding, cisregulatory, Expression quantitative trait loci (eQTL), and literature). With the matched transcriptome data, SPACE documents 17,638,113,605 peak-mRNA/lncRNA/miRNA pairs and their phenotypic association, such as prognosis or cancer subtype. Users can also predict peak-associated pathways and their role in the immune microenvironment. SPACE can serve as a useful resource to explore the roles of DNA regulatory elements and their associated transcriptional changes as well as the clinical relevance in cancer patients.The user interface of SPACE was written in R Shiny. The detailed procedures of …