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Background: Bacterial operons are considerably more complex than what were thought. At least their components are dynamically rather than statically defined as previously assumed. Here we present a computational study of the landscape of the transcriptional units (TUs) of E. coli K12, revealed by the available genomic and transcriptomic data, providing new understanding about the complexity of TUs as a whole encoded in the genome of E. coli K12. Results and conclusion: Our main findings include that (i) different TUs may overlap with each other by sharing common genes, giving rise to clusters of overlapped TUs (TUCs) along the genomic sequence; (ii) the intergenic regions in front of the first gene of each TU tend to have more conserved sequence motifs than those of the other genes inside the TU, suggesting that TUs each have their own promoters; (iii) the terminators associated with the 3' ends of TUCs tend to be Rho-independent terminators, substantially more often than terminators of TUs that end inside a TUC; and (iv) the functional relatedness of adjacent gene pairs in individual TUs is higher than those in TUCs, suggesting that individual TUs are more basic functional units than TUCs. [ABSTRACT FROM AUTHOR]

Background: Reconstruction of biological pathways is typically done through mapping well-characterized pathways of model organisms to a target genome, through orthologous gene mapping. A limitation of such pathway-mapping approaches is that the mapped pathway models are constrained by the composition of the template pathways, e.g., some genes in a target pathway may not have corresponding genes in the template pathways, the so-called "missing gene" problem. Methods: We present a novel pathway-expansion method for identifying additional genes that are possibly involved in a target pathway after pathway mapping, to fill holes caused by missing genes as well as to expand the mapped pathway model. The basic idea of the algorithm is to identify genes in the target genome whose homologous genes share common operons with homologs of any mapped pathway genes in some reference genome, and to add such genes to the target pathway if their functions are consistent with the cellular function of the target pathway. Results: We have implemented this idea using a graph-theoretic approach and demonstrated the effectiveness of the algorithm on known pathways of E. coli in the KEGG database. On all KEGG pathways containing at least 5 genes, our method achieves an average of 60% positive predictive value (PPV) and the performance is increased with more seed genes added. Analysis shows that our method is highly robust. Conclusions: An effective method is presented to find missing genes in biological pathways of prokaryotes, which achieves high prediction reliability on E. coli at a genome level. Numerous missing genes are found to be related to knwon E. coli pathways, which can be further validated through biological experiments. Overall this method is robust and can be used for functional inference. [ABSTRACT FROM AUTHOR]