疾病组织中人类孤儿基因转录本的检测相对表达量与检测频率匹配的对照有所降低

文献信息

中文摘要

人类孤儿基因注释不足且表达量低，这使得它们在疾病中的行为难以确定。我们分析了来自四个队列的配对正常与疾病RNA-seq文库，并针对一个合并参考进行定量，其中198,507个转录本中有2190个为孤儿转录本。首先对队列进行筛选，以发现两种条件之间的文库水平差异，其中一个队列（GSE40419，肺腺癌）被排除，因为测序深度、伪比对率和提交来源均因条件而异；该队列在整个过程中作为校准保留。在其余三个队列中，包括来自银屑病、喉鳞状细胞癌和肝细胞癌的151对匹配样本，我们测量了零丰度转录本比例的变化，该量不依赖于任何表达量变换。在固定检测的全局变化后，孤儿转录本相对于按丰度和跨患者检测频率匹配的非孤儿转录本失去检测，分别增加+0.0250±0.0178、+0.0553±0.0073和+0.0659±0.0122。这三个估计值同质（p=0.163），合并为+0.0544±0.0059，而应用于被排除队列的相同分析返回该值的十三倍。我们在测量水平上报告结果，并撤回本工作第一版预印本中做出的患者水平和队列特异性声明。

英文摘要

Human orphan genes are poorly annotated and lowly expressed, which makes their behavior in disease difficult to establish. We analyzed paired normal and disease RNA-seq libraries from four cohorts, quantified against a combined reference in which 2190 of 198,507 transcripts are orphan. Cohorts were first screened for library-level differences between the two conditions, and one (GSE40419, lung adenocarcinoma) was excluded because sequencing depth, pseudoalignment rate, and submission provenance all differed by condition; it is retained throughout as a calibration. In the remaining three cohorts, comprising 151 matched pairs from psoriasis, laryngeal squamous cell carcinoma, and hepatocellular carcinoma, we measured the change in the fraction of transcripts with zero abundance, a quantity that does not depend on any transformation of expression. Orphan transcripts lose detection relative to non-orphan transcripts matched on abundance and on cross-patient detection frequency, by +0.0250±0.0178, +0.0553±0.0073, and +0.0659±0.0122 once the global shift in detection is held fixed. The three estimates are homogeneous (p=0.163) and pool to +0.0544±0.0059, whereas the same analysis applied to the excluded cohort returns thirteen times that value. We report the result at the level at which it is measured, and withdraw the patient-level and cohort-specific claims made in the first preprint version of this work.