Research On LncRNA Target Gene Recognition And Clustering Of Single-cell Based On LncRNA Expression

Large-scale genomic and transcriptomic analysis shows that more than 90% of human genome sequences are transcribed,whereas only 2% of genomic sequences are capable of encoding into proteins,and the rest are non-coding RNAs.The rapid development of genome-wide sequencing technology has produced a large number of new transcripts,most of which are long-chain non-coding RNAs(lncRNAs).Studies have shown that lncRNA plays an important role in many life activities such as dosecompensation effect,epigenetic regulation,cell cycle regulation and cell differentiation regulation.Many human complex diseases are closely related to the abnormal function of lncRNA,such as cancer,neurodegenerative disease,cardiovascular disease,diabetes,etc.Traditional lncRNA high-throughput sequencing requires the acquisition of enough RNA from a large number of cells,so the sequencing results are a "whole" representation of these cells.However,due to cellular heterogeneity,there may be significant differences in the genetic information of cells of the same phenotype,and many low-abundance lncRNAs are lost in the overall characterization.To compensate for the limitations of traditional high-throughput sequencing,single-cell sequencing technology has emerged,making it possible to study the expression of lncRNA from a single cell level.This thesis deeply explores the function of lncRNA and its role in single-cell cluster analysis,which is mainly divided into the following three aspects.First,in order to understand the function of lncRNA and its possible regulatory mechanisms,this paper collected all published lncRNA papers and high-throughput sequencing data sets,constructed LncRNA2 Target database,provided a comprehensive low-throughput assay for human and mouse validation of lncRNA-target gene relationships and highthroughput sequencing data analysis for lncRNA-target gene relationships.Then,in order to study the cellular heterogeneity of lncRNA,explore the cell clustering method based on lncRNA.This paper selects the single cell transcriptome sequencing data of known cell types as a test and found that lncRNA-based single cell clustering method is better than mRNA-based aggregation.suggesting significant cellular heterogeneity in lncRNA,which can be used for cell type differentiation.Finally,based on the advantages of lncRNA to distinguish different cell types,this paper further uses lncRNA clustering method in single cell research of breast cancer,through the heterogeneity of lncRNA,clusters breast cancer cells into 7 cell subtypes.Further analysis of the differentially expressed lncRNA between different cell subtypes,combined with the lncRNA-target gene information contained in the LncRNA2 Target database,revealed the molecular mechanism of potential regulation of lncRNA in different types of breast cancer.In this paper,long-chain non-coding RNA was used as the research object to explore the mechanism of lncRNA regulation gene expression.Furthermore,the complete lncRNA-target gene database LncRNA2 Target combined with single cell sequencing data was constructed to further explore the cellular heterogeneity of lncRNA and its role in cell clustering.It was found that lncRNA has a better discrimination effect on different types of cells;Combined with single cell data analysis of breast cancer,the heterogeneity and potential regulatory mechanism of lncRNA in different types of breast cancer cells were further explored.The research of this thesis has important theoretical significance and application value.