Department of Oncology, Johns Hopkins University School of Medicine, Baltimore, Maryland 21827, USA.
Departamento de Bioqúımica e Imunologia, ICB, Universidade Federal de Minas Gerais, Belo Horizonte, Minas Gerais, 31270-901, Brazil.
Genome Res. 2020 Jul;30(7):1073-1081. doi: 10.1101/gr.254656.119. Epub 2020 Feb 20.
Long noncoding RNAs (lncRNAs) have emerged as key coordinators of biological and cellular processes. Characterizing lncRNA expression across cells and tissues is key to understanding their role in determining phenotypes, including human diseases. We present here FC-R2, a comprehensive expression atlas across a broadly defined human transcriptome, inclusive of over 109,000 coding and noncoding genes, as described in the FANTOM CAGE-Associated Transcriptome (FANTOM-CAT) study. This atlas greatly extends the gene annotation used in the original resource. We demonstrate the utility of the FC-R2 atlas by reproducing key findings from published large studies and by generating new results across normal and diseased human samples. In particular, we (a) identify tissue-specific transcription profiles for distinct classes of coding and noncoding genes, (b) perform differential expression analysis across thirteen cancer types, identifying novel noncoding genes potentially involved in tumor pathogenesis and progression, and (c) confirm the prognostic value for several enhancer lncRNAs expression in cancer. Our resource is instrumental for the systematic molecular characterization of lncRNA by the FANTOM6 Consortium. In conclusion, comprised of over 70,000 samples, the FC-R2 atlas will empower other researchers to investigate functions and biological roles of both known coding genes and novel lncRNAs.
长链非编码 RNA(lncRNA)已成为生物和细胞过程的关键协调因子。描述 lncRNA 在细胞和组织中的表达是理解其在决定表型(包括人类疾病)中的作用的关键。我们在此展示 FC-R2,这是一个全面的人类转录组表达图谱,涵盖了超过 109000 个编码和非编码基因,如 FANTOM CAGE 相关转录组(FANTOM-CAT)研究中所述。该图谱极大地扩展了原始资源中使用的基因注释。我们通过重现已发表的大型研究中的关键发现,并在正常和患病的人类样本中生成新的结果,证明了 FC-R2 图谱的实用性。特别是,我们:(a)确定了不同类别编码和非编码基因的组织特异性转录谱;(b)对 13 种癌症类型进行了差异表达分析,鉴定了可能参与肿瘤发病机制和进展的新型非编码基因;(c)确认了几种增强子 lncRNA 在癌症中的预后价值。我们的资源是 FANTOM6 联盟对 lncRNA 进行系统分子特征分析的重要工具。总之,FC-R2 图谱由超过 70000 个样本组成,将使其他研究人员能够研究已知编码基因和新型 lncRNA 的功能和生物学作用。