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Construction Of Cross-species Target Gene Prediction System Platform And Its Application Research

Posted on:2015-01-10Degree:MasterType:Thesis
Country:ChinaCandidate:J X LiuFull Text:PDF
GTID:2250330428998081Subject:Computer application technology
Abstract/Summary:PDF Full Text Request
In many tissues and organs, there is a class of about22nucleotides (nt) in length,noncoding and endogenous small molecule fragment, which is named as microRNA(abbreviated as miRNA). And because of its significant role it has played in life process ofdevelopment and apoptosis, it caused widespread concern of researchers and brought a lot ofprogress in life science research. The strong effect of miRNAs targeting on message RNA(abbreviated as mRNAs), establishing cell lineage can direct the RNA-induced silencingcomplex (abbreviated as RISC) to down-regulate gene expression by degradation of mRNAor translational inhibition.MiRNAs are key factors of multiple gene regulation mechanisms, multipledevelopmental pathways, and the basis of phenotypic determinants and inherited diseases. Sothere are a plenty of target prediction computational methods for one or more species havebeen raised which include animals, worms, fruit fly. The main features these algorithmsconsidered include the most important feature for targets identification-base pairing ofmiRNA-mRNA, site position, conservation, and minimum free energy (MFE) that is used toassess the accessibility, and complex site represents the optimal distance between the targets.However, the methods that can combine all known features and makes it as the parameteradjustment are still little.Based on computational prediction method, support of a variety of biologicalexperiments means and a lot of literature, many research teams have a system collection,statistics analysis and miRNA targeting description, by which help them establish a morecomprehensive database that contains the information of registry miRNA sequences andpredicted targets, such asTarBase. Meanwhile, there are establishment of such authority RNAgenome database like NCBI, providing support to obtain authoritative data and comparisoninformation.Recently, outbreaks of avian influenza, the rising incidence of cancer, and thegroundbreaking discovery of plant miRNAs entering human body by Chenyu Zhang groupand their proposing of cross-species transmission mechanisms mediated by exogenousmiRNA all indicate the importance of application research on target gene prediction. While it has been suggested that host miRNAs may down-regulate viral gene expression as an antiviraldefense mechanism, such a mechanism has not been explored in the influenza virus forhuman flu studies. Gastric cancer, as one of the most common malignant tumor has a seriousthreat for people’s health. As predicted by the biological experiments on both of above willhave a problem of consumption of wealth and timing, so computational studies can providesome insight. And a discovery of plant miRNAs can enter the human blood and organs byway of daily food intake, which also make cross-species target gene prediction become a hottopic.However, there is little method for cross-species prediction, so we improve traditionalfeatures, come up with a3-dimensional energy feature and a penalty function algorithm basedon position and gap size, and learn the advantages of database to construct a cross-speciestarget gene prediction platform, which can balance the sensitive and specificity and has a lowtime complexity.In addition, we have an application research by using our platform. We analyze themechanism of human miRNAs regulating viral RNAs by the predicted target binding. Weguide a biological experiment and verify the accuracy of the forecasts of our platform by thepredicted position of gastric cancer targets, and analyz the possibility of hsa-miR-625up-regulation by the predicted position of protein targets. We also predict the possibility of aplant miRNA regulate human mRNA by searching which protein the predicted target genesbelong.Our platform provides a well support for biological experiments and save a lot of time,labor and material resources. Now research of cross-species target gene prediction is still inthe initial stage and many predicted results need to be a further verify, but it will has a greatprospects on drug design and disease treatment base on this.
Keywords/Search Tags:microRNA, cross-species, target prediction, gastric cancer, influenza virus
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