Construction Of Gene Alternative Splicing Regulatory Networks

Alternative splicing is an important mechanism of gene regulation in eukaryotes.Alternative splicing make gene produce multiple gene variants, and it can encode multiple proteins, that is greatly enriched the types of protein function. Researches showed that alternative splicing is closely related with many diseases, including spinal muscular atrophy,retinitis pigmentosa, Prader-Willi cell migration, syndrome and cancer cell growth regulation,hormonal response gene expression, cell death and chemotherapeutic response changes.Therefore, the researches on alternative splicing will contribute to the understanding of the regulatory relationships between genes and proteins in essence to researchers,and find better treatments for cancer and other major diseases.Alternative splicing regulation network is the extension of gene regulatory network, and it used to describe gene regulatory interaction between variants. The construction of alternative splicing regulation network is the basis of studying the regulation of alternative splicing mechanism deeply. This paper researches the construction of alternative splicing regulation network:(?)Processing of Gene expression data. Based on the Tophat software packages doing sequence alignment of RNA-seq data. Sequence alignment is the important and key step among transcriptional analysis, which results directly affect the accuracy and precision of following experiments. In this paper, after comparing the several existing sequence alignment software tools, considering the characteristics of the data, puts forward a positioning software selection criteria, according to the criterion and matching software, choose the most suitable positioning software project and align RNA-seq sequence data to the reference genome sequence. The experimental results show that, the Tophat software is not only do well in matching with the reading section, but also accurately identify exon binding region, and has the advantages of fast speed, suitable for short read data matching, therefore, using Tophat software could well meet the characteristics of data in this paper.(?)Estimation of gene expression based on Cufflinks. In this paper, I chose the Cufflinks software package to calculate gene expression value based on RPKM algorithm(Read Per Kb per Million mapped reads). First of all, using the Cufflinks to assembly for single transcript and then, make a fusion transcript from multiple single transcripts, calculate expression of every variant of the gene and do the differential analysis. The experimental results show that the method can effectively identify the differentially expressed genes, which can provide the basis for the prediction of alternative splicing events.(?)Predict the relationship between the gene alternative splicing variants based on correlation analysis. Correlation analysis is a statistical method and studying whether there is a relationship between two random variables. Firstly, by using the Pearson correlation algorithm, calculating the correlation coefficient between the gene variant, when the correlation coefficient is larger than the preset threshold, connect an edge between two gene variants and then judge the existing positive or negative correlation. Lastly, according to the results of Pearson correlation analysis, predict the gene regulatory relations between variants.(?)Construct the gene splicing regulatory networks based on Bayesian network.Through the Pearson correlation analysis we found the gene variants which correlation coefficient is greater than the set the threshold, and establish Bayesian network using gene isoforms with correlation and analysis further in order to found the regulatory relationships between multiple gene variants. The intelligent calculation method simulated the regulatory interactions of the regulatory interactions of several key genes of Candida albicans in different conditions, and reflected alternative splicing regulation mechanism of different stress environment of Candida albicans, provided a theoretical guidance for experimental biologists for further study of this species.