Identification Of Gene Regulatory Networks In Various Human Tumor Cells

Gene Regulatory Network(GRN)is a complex network formed by the regulation of genes.The transcription status of tumor cells and normal cells are often different.Therefore,the identification and analysis of tumor-specific GRN is important for the diagnosis and treatment of cancer.This article collected gene expression data of 33 different tumors in the TCGA database,and identified some transcription factors and GRNs that are closely related to cancer through bioinformatics methods.By comparing different tumor GRN,we identified 25highly conserved transcription factors in pan-cancer species and 16 transcription factors with very different regulatory networks.By comparing each tumor with its adjacent tissues,60 tumor-specific GRNs were identified,then We mainly described the RELA-related GRN.These specific GRNs may provide new potential biomarkers for cancer diagnosis.In addition,we also analyzed the characteristics and functions of GRN at the single-cell level under different conditions based on a large-scale single-cell RNA sequencing data,and found that different cell subtypes have their own specific GRNs.For example,by analyzing single-cell RNA sequencing data of non-small cell lung cancer cells,we identified 6,4,and 2 specific GRNs in CD8~+,CD4~+Treg and CD4~+Tconv,respectively.In view of the importance of GRN,we collected 184 gene expression data under different physiological and pathological conditions based on public data platforms such as TCGA,GTEx,and GEO.Then we constructed a free GRN database GRNdb(www.grndb.com).It is convenient for researchers to further analyze the GRN under relevant conditions.The database currently includes 143 human tissues with different normal and disease conditions,involving 17 million transcription factor-target gene interaction pairs,41 mouse tissues with nearly 2.8 million transcription factor-target gene interaction pairs.Through the GRNdb database,you can conveniently and intuitively query and analyze the regulatory relationship and expression status of different genes under different conditions.In general,we have systematically analyzed GRNs in various tumor cells,and identified some common and specific GRNs in tumors.We also analyzed the role of GRN in cell typing,and constructed the GRNdb database to promote the development of the research field of gene regulatory networks.