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4From Promoter Analysis to Transcriptional RegulatoryNetwork Prediction Using PAINTGregory E. Gonye, Praveen Chakravarthula, James S. Schwaber,and Rajanikanth VadigepalliSummaryHighly parallel gene-expression analysis has led to analysis of gene regulation, in particularcoregulation, at a system level. Promoter analysis and interaction network toolset (PAINT) wasdeveloped to provide the biologist a computational tool to integrate functional genomics data, forexample, from microarray-based gene-expression analysis with genomic sequence data to carryout transcriptional regulatory network analysis (TRNA). TRNA combines bioinformatics, used toidentify and analyze gene-regulatory regions, and statistical significance testing, used to rank thelikelihood of the involvement of individual transcription factors (TF), with visualization tools toidentify TF likely to play a role in the cellular process under investigation. In summary, given a listof gene identifiers PAINT can: (1) fetch potential promoter sequences for the genes in the list, (2)find TF-binding sites on the sequences, (3) analyze the TF-binding site occurrences for over/underrepresentationcompared with a reference, with or without coexpression clustering information,and (4) generate multiple visualizations for these analyses. At present, PAINT supports TRNA ofthe human, mouse, and rat genomes. PAINT is currently available as an online, web-based servicelocated at: http://www.dbi.tju.edu/dbi/tools/paint.Key Words: Clustering; gene expression; gene regulation; network analysis; pattern recognition;transcription factors.1. IntroductionBiomedical scientists have a long standing interest in acquiring gene listsbecause the character of differentiated cellular function and disease is often welldescribed in this fashion. Organ system structure and function are the product ofvariations in differentiated gene expression (and gene-expression products) ininteraction with the environment. Disruption of these distinct patterns of activegenes can lead to organ disease and changes in behavior. Thus, associating patternsof gene activity (i.e., gene lists) with structure and function is a key ongoingFrom: Methods in Molecular Biology, vol. 408: Gene Function AnalysisEdited by: M. Ochs © Humana Press Inc., Totowa, NJ49
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4From Promoter Analysis to Transcriptional RegulatoryNetwork Prediction Using PAINTGregory E. Gonye, Praveen Chakravarthula, James S. Schwaber,and Rajanikanth VadigepalliSummaryHighly parallel gene-expression analysis has led to analysis of gene regulation, in particularcoregulation, at a system level. Promoter analysis and interaction network toolset (PAINT) wasdeveloped to provide the biologist a computational tool to integrate functional genomics data, forexample, from microarray-based gene-expression analysis with genomic sequence data to carryout transcriptional regulatory network analysis (TRNA). TRNA combines bioinformatics, used toidentify and analyze gene-regulatory regions, and statistical significance testing, used to rank thelikelihood of the involvement of individual transcription factors (TF), with visualization tools toidentify TF likely to play a role in the cellular process under investigation. In summary, given a listof gene identifiers PAINT can: (1) fetch potential promoter sequences for the genes in the list, (2)find TF-binding sites on the sequences, (3) analyze the TF-binding site occurrences for over/underrepresentationcompared with a reference, with or without coexpression clustering information,and (4) generate multiple visualizations for these analyses. At present, PAINT supports TRNA ofthe human, mouse, and rat genomes. PAINT is currently available as an online, web-based servicelocated at: http://www.dbi.tju.edu/dbi/tools/paint.Key Words: Clustering; gene expression; gene regulation; network analysis; pattern recognition;transcription factors.1. IntroductionBiomedical scientists have a long standing interest in acquiring gene listsbecause the character of differentiated cellular function and disease is often welldescribed in this fashion. Organ system structure and function are the product ofvariations in differentiated gene expression (and gene-expression products) ininteraction with the environment. Disruption of these distinct patterns of activegenes can lead to organ disease and changes in behavior. Thus, associating patternsof gene activity (i.e., gene lists) with structure and function is a key ongoingFrom: Methods in Molecular Biology, vol. 408: Gene Function AnalysisEdited by: M. Ochs © Humana Press Inc., Totowa, NJ49