The Study Of LncRNA Implicatied In ESCC And Construction Of A Platform For Model Organism Selection

With the development of high-throughput biochip and sequencing techniques and the reduction in prices per sample,a large number of “omics” data have been generated,providing a global view with rich information on diseases and their diagnosis.Effective integration and analysis of different levels of biomedical big data for human disease research is an important scientific issue of concern.In this study,by using biomedical big data we investigated the roles of lncRNAs in the development of ESCC,and constructed a platform for experimental scientists to select appropriate animal models for study of human biomedical mechanism.Esophageal squamous cell carcinoma(ESCC),which is a highly aggressive malignancy with poor prognosis cancer,is more common in the developing world,especially in China.Integrated analysis of biomedical big data to detect potential ESCC-related lncRNAs would help us understand the mechanisms of the disease.In addition,with the availability of whole-genome sequences for an increasing number of animal models,the need for better use of animal models for translational research has become imperative.This study uncovered the key roles of lncRNAs as competing endogenous RNA(ceRNA)implicated in ESCC.Two clinically relevant subtypes of ESCC were identified based on expression profiles of lncRNA and mRNA genes.The data suggest EGFR might be a potential marker for the subtypes of ESCC.ESCC subtype-specific differential crosstalk networks between mRNA and lncRNA were constructed to reveal dynamic changes of their crosstalks mediated by miRNA during tumorigenesis.The key lncRNAs(PVT1,LINC00240,etc.)were identified based on the networks and the “loss” of PVT1-PTTG1 and LINC00240-KLF3 crosstalks were illustrated as the related events implicated in development of two subtypes of ESCC.Furthermore,ESCC subtype-specific modules of differential mRNA-lncRNA crosstalks were uncovered,and functional cooperation of multiple lncRNAs were found in different biological processes,such as neuron development and mitotic cell cycle,which were associated with ESCC.In addition,we developed a bioinformatics platform for experimental scientists to select appropriate animal models to study human molecular mechanism—SysFinder,which is a human problem-oriented platform for searching,comparing and assisted designing of appropriate animal models based on systematic similarity.It provides four main functions:(1)Offer a systematic comparison of function of human genes involved in scientific topics with those of animal models based on multi-level systematic similarity indexes(2)Provide homologous relationships and species-specific information covered by scientific topics(3)Search sgRNA and generates homolog arm,which are used by CRISPR-Cas9 systems and assist in introducing clinically relevant SNPs or protein functional sites of human to model organism for the development of new animal models(4)Find suitable scientific topics based on a selected animal model.Furthermore,several case studies illustrated the power of SysFinder in selecting animal models.In conclusion,this study uncovered the roles of competitive endogenous lncRNAs implicated in different subtypes of ESCC,providing a new idea for exploring the mechanism of ESCC.Furthermore,SysFinder platform has the power in the pathological comparison between human and animal models,offering a new method to help researchers select better animal models or mouse strains for conditional investigation on human research.