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Item The distinctive signatures of promoter regions and operon junctions across prokaryotes(2006-08) Janga, Sarath Chandra; Lamboy, Warren F.; Huerta, Araceli M.; Moreno-Hagelsieb, GabrielHere we show that regions upstream of first transcribed genes have oligonucleotide signatures that distinguish them from regions upstream of genes in the middle of operons. Databases of experimentally confirmed transcription units do not exist for most genomes. Thus, to expand the analyses into genomes with no experimentally confirmed data, we used genes conserved adjacent in evolutionarily distant genomes as representatives of genes inside operons. Likewise, we used divergently transcribed genes as representative examples of first transcribed genes. In model organisms, the trinucleotide signatures of regions upstream of these representative genes allow for operon predictions with accuracies close to those obtained with known operon data (0.8). Signature-based operon predictions have more similar phylogenetic profiles and higher proportions of genes in the same pathways than predicted transcription unit boundaries (TUBs). These results confirm that we are separating genes with related functions, as expected for operons, from genes not necessarily related, as expected for genes in different transcription units. We also test the quality of the predictions using microarray data in six genomes and show that the signature-predicted operons tend to have high correlations of expression. Oligonucleotide signatures should expand the number of tools available to identify operons even in poorly characterized genomes.Item Nebulon: a system for the inference of functional relationships of gene products from the rearrangement of predicted operons(2005-04) Janga, Sarath Chandra; Collado-Vides, Julio; Moreno-Hagelsieb, GabrielSince operons are unstable across Prokaryotes, it has been suggested that perhaps they re-combine in a conservative manner. Thus, genes belonging to a given operon in one genome might re-associate in other genomes revealing functional relationships among gene products. We developed a system to build networks of functional relationships of gene products based on their organization into operons in any available genome. The operon predictions are based on inter-genic distances. Our system can use different kinds of thresholds to accept a functional relationship, either related to the prediction of operons, or to the number of non-redundant genomes that support the associations. We also work by shells, meaning that we decide on the number of linking iterations to allow for the complementation of related gene sets. The method shows high reliability benchmarked against knowledge-bases of functional interactions. We also illustrate the use of Nebulon in finding new members of regulons, and of other functional groups of genes. Operon rearrangements produce thousands of high-quality new interactions per prokaryotic genome, and thousands of confirmations per genome to other predictions, making it another important tool for the inference of functional interactions from genomic context.Item Prediction and evolution of transcription factors and their evolutionary families in prokaryotes(2007-05) Janga, Sarath ChandraTranscription factors (TFs) play an important role in the genetic regulation of transcription in response to internal and external cellular stimulus even in a simple bacterium like Escherichia coli [1]. However little is known about their functional roles, expression dynamics and evolutionary scenarios on a large scale, even in a well studied model organisms. In this short tutorial, I will first talk about the prediction of transcription factors, which form the core of the regulatory repertoires in prokaryotes, responsible for controlling the expression of genes/transcription units by binding to their cis-regulatory regions. I will present different commonly used sequenced-based approaches to predict TFs in prokarya and discuss a simple rule of thumb to identify the putative regulatory role played by a TF based on its protein sequence alone [2-6]. I will discuss on some important properties of prokaryotic TFs which distinguish them apart from rest of the protein coding genes. The second part of the talk would concentrate on the evolutionary conservation of TFs and TF families across genomes and the implications of the observations on the phenotypic adaptation of species to different niches [3,7,8]. Finally, I will discuss some future perspectives in this area of research.