title: A statistical framework for improving genomic annotations of transposon mutagenesis (TM) assigned essential genes.
abstract: Whole-genome transposon mutagenesis (TM) experiment followed by sequence-based identification of insertion sites is the most popular genome-wise experiment to identify essential genes in Prokaryota. However, due to the limitation of high-throughput technique, this approach yields substantial systematic biases resulting in the incorrect assignments of many essential genes. To obtain unbiased and accurate annotations of essential genes from TM experiments, we developed a novel Poisson model based statistical framework to refine these TM assignments. In the model, first we identified and incorporated several potential factors such as gene length and TM insertion information which may cause the TM assignment biases into the basic Poisson model. Then we calculated the conditional probability of an essential gene given the observed TM insertion number. By factorizing this probability through introducing a latent variable the real insertion number, we formalized the statistical framework. Through iteratively updating and optimizing model parameters to maximize the goodness-of-fit of the model to the observed TM insertion data, we finalized the model. Using this model, we are able to assign the probability score of essentiality to each individual gene given its TM assignment, which subsequently correct the experimental biases. To enable our model widely useable, we established a user-friendly Web-server that is accessible to the public: http://research.cchmc.org/essentialgene/.
authors: Division of Epidemiology and Biostatistics, Department of Environmental Health, University of Cincinnati Medical Center, 3223 Eden Av. ML 56, Cincinnati, OH, 45267-0056, USA, dengjn@mail.uc.edu.
authors: Jingyuan
authors: J
authors: Deng
mesh_terms: D004251:DNA Transposable Elements / Q000235:genetics*; D020043:Genes, Essential; D023281:Genomics / Q000379:methods*; D058977:Molecular Sequence Annotation; D016254:Mutagenesis, Insertional / Q000235:genetics*; D012984:Software; D013223:Statistics as Topic
chemical_list: D004251:DNA Transposable Elements