Department of Preventative Medicine, Zhejiang Provincial Key Laboratory of Pathological and Physiological Technology, Medicine School of Ningbo University, Ningbo, Zhejiang, China.
Zhejiang Provincial Key Laboratory of Pathophysiology, School of Medicine, Ningbo University, Zhejiang, Ningbo, China.
Bioinformatics. 2019 Nov 1;35(21):4344-4349. doi: 10.1093/bioinformatics/btz230.
Genome-scale CRISPR/Cas9 system has been a democratized gene editing technique and widely used to investigate gene functions in some biological processes and diseases especially cancers. Aiming to characterize gene aberrations and assess their effects on cancer, we designed a pipeline to identify the essential genes for pan-cancer.
CRISPR screening data were used to identify the essential genes that were collected from published data and integrated by Robust Rank Aggregation algorithm. Then, hypergeometrics test and random walks with restart (RWR) were used to predict additional essential genes on broader scale. Finally, the expression status and potential roles of these genes were explored based on TCGA portal and regulatory network analysis.
We collected 926 samples from 10 CRISPR-based screening studies involving 33 different types of cancer to identify cancer-essential genes, which consists of 799 protein-coding genes (PCGs) and 97 long non-coding RNAs (lncRNAs). Then, we constructed a 'bi-colored' network with both PCGs and lncRNAs and applied it to predict additional essential genes including 495 PCGs and 280 lncRNAs on a broader scale using hypergeometrics test and RWR. After obtaining all essential genes, we further investigated their potential roles in cancer and found that essential genes have higher and more stable expression levels, and are associated with multiple cancer-associated biological processes and survival time. The regulatory network analysis detected two intriguing modules of essential genes participating in the regulation of cell cycle and ribosome biogenesis in cancer.
Supplementary data are available at Bioinformatics online.
基因组规模的 CRISPR/Cas9 系统已成为一种民主化的基因编辑技术，广泛用于研究某些生物学过程和疾病（尤其是癌症）中的基因功能。为了描述基因异常并评估其对癌症的影响，我们设计了一个用于鉴定泛癌必需基因的流程。
CRISPR 筛选数据用于从已发表的数据中识别必需基因，并通过稳健排名聚合算法进行整合。然后，使用超几何检验和随机游走重启（RWR）在更广泛的范围内预测额外的必需基因。最后，根据 TCGA 门户和调控网络分析，探索这些基因的表达状态和潜在作用。
我们从涉及 33 种不同类型癌症的 10 项基于 CRISPR 的筛选研究中收集了 926 个样本，以鉴定癌症必需基因，其中包括 799 个蛋白编码基因（PCGs）和 97 个长非编码 RNA（lncRNAs）。然后，我们构建了一个“双色”网络，同时包含 PCGs 和 lncRNAs，并使用超几何检验和 RWR 在更广泛的范围内预测额外的必需基因，包括 495 个 PCGs 和 280 个 lncRNAs。获得所有必需基因后，我们进一步研究了它们在癌症中的潜在作用，发现必需基因具有更高和更稳定的表达水平，并与多个与癌症相关的生物学过程和生存时间相关。调控网络分析检测到两个有趣的必需基因模块，它们参与了癌症中细胞周期和核糖体生物发生的调控。
补充数据可在生物信息学在线获取。
