BACKGROUND: The recent flood of data from genome sequencing and functional genomics has given rise to new field, bioinformatics, which combines elements of biology and computer science. OBJECTIVES: Here we propose a definition for this new field and review some the research that is being pursued, particularly in relation to transcriptional regulatory systems. METHODS: Our definition is as follows: Bioinformatics is conceptualizing biology in terms of macromolecules (in the sense of physical-chemistry) and then applying "informatics" techniques (derived from disciplines such as applied maths, computer science, and statistics) to understand and organize the information associated with these molecules, on a large-scale. RESULTS & CONCLUSIONS: Analyses in bioinformatics predominantly focus on three types of large datasets available in molecular biology: macromolecular structures, genome sequences, and the results of functional genomics experiments (eg expression data). Additional information includes the text of scientific papers and "relationship data" from metabolic pathways, taxonomy trees, and proteinprotein interaction networks. Bioinformatics employs a wide range of computational topics including sequence and structural alignment, database design and data mining, macromolecular geometry, phylogenetic tree construction, prediction of protein structure and function, gene finding, and expression data clustering. The emphasis is on approaches that integrate a variety of computational techniques and heterogeneous data sources. Finally, bioinformatics is a practical discipline. We survey some representative applications, such as finding homologues, designing drugs, and performing large-scale censuses. Additional information pertinent to the review is available over the w...

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A novel family of transcription factors responsible for regulation of various aspects of NAD synthesis in a broad range of bacteria was identified by comparative genomics approach. Regulators of this family (here termed NrtR for Nudix-related transcriptional regulators), currently annotated as ADPribose pyrophosphatases from the Nudix family, are composed of an N-terminal Nudix-like effector domain and a C-terminal DNA-binding HTH-like domain. NrtR regulons were reconstructed in diverse bacterial genomes by identification and comparative analysis of NrtR-binding sites upstream of genes involved in NAD biosynthetic pathways. The candidate NrtR-binding DNA motifs showed significant variability between microbial lineages, although the common consensus sequence could be traced for most of them. Bioinformatics predictions were experimentally validated by gel mobility shift assays for two NrtR family representatives. ADP-ribose, the product of glycohydrolytic cleavage of NAD, was found to suppress the in vitro binding of NrtR proteins to their DNA target sites. In addition to a major role in the direct regulation of NAD homeostasis, some members of NrtR family appear to have been recruited for the regulation of other metabolic pathways, including sugar pentoses utilization and biogenesis of phosphoribosyl pyrophosphate. This work and the accompanying study of NiaR regulon demonstrate significant variability of regulatory strategies for control of NAD metabolic pathway in bacteria.

non-parametric model for transcription factor

In this report we provide an overview of known techniques for discovery of patterns of biological sequences (DNA and proteins). We also provide biological motivation, and methods of biological verification of such patterns. Finally we list publicly available tools and databases for pattern discovery. On-line supplement is available through http://monod.uwaterloo.ca/supplements/00motif . Contents 1

Regulation of gene expression of lytic bacteriophage φYS40 that infects thermophilic bacterium Thermus thermophilus was investigated and three temporal classes of phage genes-- early, middle, and late-- were revealed. φYS40 does not encode a DNA-dependent RNA polymerase (RNAP) and must rely on host RNAP for transcription of its genes. Bioinformatic analysis using a model of Thermus promoters predicted 43 putative σ A-dependent-10/-35 class phage promoters. A randomly chosen subset of those promoters was shown to be functional in vivo and in vitro and to belong to the early temporal class. Macroarray analysis, primer extension, and bioinformatic predictions identified 36 viral middle and late promoters. These promoters have a single common consensus element, which resembles host σ A RNAP holoenzyme –10 promoter consensus element sequence. The mechanism responsible for the temporal control of the three classes of promoters remains unknown, since host σ A RNAP holoenzyme-purified from either infected or uninfected cells efficiently transcribed all φYS40 promoters in vitro. Interestingly, our data showed that during infection, there is a significant increase

Genomics of bacteria and archaea: the emerging dynamic view of the prokaryotic world

doi:10.1093/nar/gkn589 Predicting transcription factor specificity with all-atom models