Comprehensive Analysis and Prediction of the Essential Genes in Human Cancer Cells

Genome-scale CRISPR/Cas9 system has been a democratized gene editing technique and widely used to investigate the gene functions in some biological processes and diseases especially cancers. Cancer is a complex disease caused by the accumulation of genetic and epigenetic aberrations. Aiming to characterize such aberrations and assess their effects on cancer, we collected data from 10 published CRISPR-based screening studies involving in multiple cancer cell lines, identified a part of the cancer-essential genes including 799 protein-coding genes (PCGs) and 97 long noncoding RNAs (lncRNAs). Then, we constructed a bi-colored network with the essential genes as vertices and applied it to predict additional essential genes including 495 PCGs and 280 lncRNAs on a broader scale using hypergeometrics test and random walks with restart. After obtaining all the essential genes, we further investigate their features from the aspects of gene expression, histone modification, transcription factor binding activity, functional enrichment, and network topological analysis. Finally, we constructed the lncRNA-centric regulatory network based on the obtained essential genes and extracted some modules from it to specialize the gene functions. Most of the essential genes were related with cell cycle and ribosome biogenesis in cancer, which can provide significant clues for the cancer-associated aberrations characterization and be a critical penetration point to uncover the mysterious genetic mechanisms in cancer initiation and progression. Funding: This work is supported by The National Natural Science Foundation of China (No.31301084), The Natural Science Foundation of Zhejiang Province (No.LQ13C060002), The Natural Science Foundation of Ningbo (No.2017A610154), The Scientific Innovation Team Project of Ningbo (No.2016C51001), The Student Research and Innovation Program of Ningbo University (No.2018SRIP1904) and K.C.Wong Magna Fund in Ningbo University. Declaration of Interest: The authors declare that they have no competing interests.