Identification Of Candidate Genes Associated With Liver Disease Via Single-cell Transcriptomics

BackgroundThe liver is one of the organs with the most extensive functions in the human body and it is the central hub of many physiological functions.It is indispensable in metabolism,detoxification,immunity and other aspects.With the development of society,the morbidity of liver disease is booming year by year,which has become a major threat to the life and health of people.However,due to the heterogeneity of liver,the exact molecular mechanisms of liver disease still keep indistinct and the effective treatments are still lacking.ObjectivesAt present,there have been a lot of researches on the single-cell RNA sequencing of liver around the world,and an abundant of data resources have been accumulated,which provide convenience for researchers to communicate and learn with each other.I desire to utilize the data to correlate liver-related diseases with various types of cell populations in the liver,find novel genes related with liver diseases,and deepen our comprehension about liver diseases.MethodsBioinformatical methods have been used to integrate the data of some studies on liver single-cell transcriptome from three different researchs.At first,quality control was carried out to filter those inferior cells,and normalization was implemented.Then,the software and algorithm were used to complete the imputation of genes expression matrixs.Finally,cell clustering was reconducted and all the conventional liver cell populations were identified.The occurrence of one disease is commonly associated with a certain cell type.By comparing the expression of known genes associated with corresponding diseases in clusters of cells,we identified disease genes that were highly expressed only in a single cell type,and revealed some cell types specifically affiliated with several liver diseases.There are many genes which are expressed uniquely in each type of cells,and the interactions were analyzed between these unique genes and previously known hepatopathy genes to find which are strongly correlated.Under the circumstances,we have identified several new genes associated with liver disease.Results1.The present research has identified several cell types associated with liver diseases.Besides those carbohydrate metabolism-related diseases—glycogen storage disease(GSD)and congenital disorder of glycosylation(CDGIt),those diseases about bile—congenital bile acid synthesis defect-2(CBAS2)and progressive familial intrahepatic cholestasis-3(PFIC3)have a strong correlation with hepatocytes.Nevertheless,cryptogenic cirrhosis and polycystic kidney and hepatic disease are closely connected with bile duct cells.2.The present research has perceived some candidate hepatopathy genes,AKR1C1 and AKR1C4 are tied up with congenital bile acid synthesis defect-2,KRT7 and KRT19 are inextricably associated with cirrhosis,while ORM2 is associated with Budd-Chiari syndrome.3.The present research has identified global mutation frequencies of ORM2 mutation loci—rs3762056 and rs10982156,and the mutation frequencies in Africa and Asia are higher than those in America.4.The present research has figured out the expression of genes related to P450-drug metabolism and detoxification pathway in diverse types of cells from Homo sapiens and Macaca fascicularis,and found these genes are deeply involved with hepatocytes in both species.However,in Homo sapiens,periportal hepatocytes are dominant,while in Macaca fascicularis,central venous hepatocytes have the uppermost expression.ConlusionThis study provides a reference and guidance for finding new genes related to liver diseases,ulteriorly deepens our knowledge and understanding on liver diseases,and contributes to provide new targets or ideas for the treatments of hepatopathy,even for the related researches on other organ diseases.