Mounting evidence suggests several diseases and biological processes target transcription termination to misregulate gene expression. Disruption of transcription termination leads to readthrough transcription past the 3′ end of genes, which can result in novel transcripts, changes in epigenetic states and altered 3D genome structure. We developed Automatic Readthrough Transcription Detection (ARTDeco), a tool to detect and analyze multiple features of readthrough transcription from RNA-seq and other next-generation sequencing (NGS) assays that profile transcriptional activity. ARTDeco robustly quantifies the global severity of readthrough phenotypes, and reliably identifies individual genes that fail to terminate (readthrough genes), are aberrantly transcribed due to upstream termination failure (read-in genes), and novel transcripts created as a result of readthrough (downstream of gene or DoG transcripts). We used ARTDeco to characterize readthrough transcription observed during influenza A virus (IAV) infection, validating its specificity and sensitivity by comparing its performance in samples infected with a mutant virus that fails to block transcription termination. We verify ARTDeco’s ability to detect readthrough as well as identify read-in genes from different experimental assays across multiple experimental systems with known defects in transcriptional termination, and show how these results can be leveraged to improve the interpretation of gene expression and downstream analysis. Applying ARTDeco to a gene expression data set from IAV-infected monocytes from different donors, we find strong evidence that read-in gene-associated expression quantitative trait loci (eQTLs) likely regulate genes upstream of read-in genes. This indicates that taking readthrough transcription into account is important for the interpretation of eQTLs in systems where transcription termination is blocked. ARTDeco aids researchers investigating readthrough transcription in a variety of systems and contexts.

中文翻译：

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ARTDeco：自动通读转录检测。

越来越多的证据表明，多种疾病和生物过程以转录终止为目标，以错误调节基因表达。转录终止的破坏导致基因 3' 端的通读转录，这可能导致新的转录本、表观遗传状态的变化和 3D 基因组结构的改变。我们开发了自动通读转录检测 (ARTDeco)，这是一种用于检测和分析来自 RNA-seq 和其他描述转录活性的下一代测序 (NGS) 分析的通读转录的多个特征的工具。ARTDeco 稳健地量化通读表型的全局严重性，并可靠地识别未能终止的单个基因（通读基因），由于上游终止失败（读入基因）而异常转录，以及由于通读而创建的新转录本（基因或 DoG 转录本的下游）。我们使用 ARTDeco 来表征在甲型流感病毒 (IAV) 感染期间观察到的通读转录，通过比较其在感染了未能阻止转录终止的突变病毒的样本中的表现来验证其特异性和敏感性。我们验证了 ARTDeco 检测通读的能力，以及从具有已知转录终止缺陷的多个实验系统中的不同实验分析中识别读入基因的能力，并展示了如何利用这些结果来改进基因表达和下游分析的解释。将 ARTDeco 应用于来自不同供体的 IAV 感染单核细胞的基因表达数据集，我们发现强有力的证据表明读入基因相关表达数量性状位点 (eQTL) 可能调节读入基因上游的基因。这表明考虑通读转录对于转录终止被阻断的系统中 eQTL 的解释很重要。ARTDeco 帮助研究人员研究各种系统和环境中的通读转录。