Computer software for eukaryotic promoter analysis.
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Biomedical subjects
Publications and source records attributed to D S Prestridge.
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SIGNAL SCAN is a program that utilizes transcription factor databases to find potential transcription factor binding sites in DNA sequences. The program is now in its fourth version. SIGNAL SCAN 4 now includes, in addition to the Transcription Factor Database, the TRANSFAC and IMD (Information Matrix Database) databases. In addition, it now accepts GCG and FASTA formatted DNA sequences in addition to Staden formatted sequences. SIGNAL SCAN is available for both IBM-compatible PC and Unix workstation platforms.
A computer program, PROMOTER SCAN, has been developed to recognize a high percentage of Pol II promoter sequences while allowing only a small rate of false positives. A total of 167 primate Pol II promoter sequences, obtained from the Eukaryotic Promoter Database, and 999 primate non-promoter sequences, obtained from the GenBank sequence databank, were used in the analysis. Both promoter and non-promoter sequences were analyzed for the comparative density of each unique mammalian transcription factor binding site listed in the Ghosh Transcription Factor Database. The density of each of these binding sites was then used to derive a ratio of density of each transcriptional element in promoter compared to non-promoter sequences. The combined individual density ratios of all binding sites were then collectively used to build a scoring profile called the Promoter Recognition Profile. This profile, used in combination with a weighted matrix for scoring a TATA box, was then used by the PROMOTER SCAN program to test the prediction of promoter sequences and the ability of the computer program to discriminate them from non-promoter sequences. When the promoter cutoff score was set so that 70% of promoters were recognized correctly by the program, a false positive rate of about 1/5600 bases was observed in the non-promoter sequence set. PROMOTER SCAN is now being developed for public distribution.
SIGNAL SCAN is a program that utilizes a transcription factor database to find potential transcription factor binding sites in DNA sequences. The program is now in its third version. The SIGNAL SCAN transcription factor database format has changed and the program output format has been improved. New features allow the user to update the SIGNAL SCAN database automatically, to retrieve original journal citations and to develop user signal databases. The program now uses an indexing algorithm, improving scanning speed by a factor of 3. SIGNAL SCAN is now network compatible and is available for IBM-compatible PC, Unix and VMS platforms.
Using data currently available from transcriptional element (TE) databases, we have analyzed the density of these elements in both promoter and non-promoter sequences obtained from the GenBank sequence database. The density of putative TEs in non-promoter sequences was about 16% higher than that seen in pseudo-random DNA sequences. Promoter TE density from the transcription startsite to 100 basepairs upstream was found to be about 42% higher than in non-promoter sequences. However, the extensive overlap of putative TE densities between promoters and non-promoters confounds an attempt to use TE density as a simple discriminator.
SIGNAL SCAN is a program that has been developed to aid the molecular biologist in determining what eukaryotic transcription factor elements (and other significant elements) may exist in a DNA sequence under investigation. The program uses flatfile databases of these elements. SIGNAL SCAN is most useful for analyzing mammalian sequences due to the prevalence of mammalian elements in the database. Elements not found in the SIGNAL SCAN database may be entered by the user. SIGNAL SCAN uses both specific sequence elements derived from biochemical characterization and elements from derived consensus sequences to match against a user input DNA sequence. While any DNA sequence element matching an element in the SIGNAL SCAN database will be reported by the program, the determination of the biological relevance of the element is left up to the investigator.
When F9 embryonal carcinoma (EC) cells are infected with retroviral vectors, the efficiency of expression of selectable genes is considerably lower than that in mouse fibroblasts infected with the same retroviral vectors. In this study, several retroviral vectors with regulatory sequences placed immediately 5' to a selectable gene were constructed, packaged, and used to infect mouse fibroblasts and F9 EC cells. With selection as an assay, there was a hierarchy of relative expression in F9 cells compared with that in mouse fibroblasts. These internally placed regulatory sequences are the source of the mRNAs detected in F9 EC cells, while both retroviral long-terminal-repeat promoters and internal promoters are the source of steady-state mRNAs in mouse fibroblasts. This effect was observable with both the internally placed herpes simplex virus thymidine kinase promoter and the Moloney murine leukemia virus promoter.