BMC Genomics 2008, 9:339 http://www.biomedcentral.com/1471-2164/9/339 Utility As with most bioinformatics projects, the generation of the PRFdB engenders more questions than answers. Most importantly, why is this database of useful to anyone out- side of the frameshifting community? The response is that -1 PRF represents fundamental mechanism for the regula- tion of gene expression at post-transcriptional gene with far-reaching and broad impact. Thus, the PRFdB repre- sents a resource that is useful and available to any researcher interested in how their gene or pathway of interest might be regulated at this level. Here, we have sought to simplify such inquiries by constructing a user- friendly web-based interface. The other major question concerns what the user might do following identification of a potential -1 PRF signal in a gene of interest. The clas- sical "bench-based" approach that we are currently fol- lowing is to clone the element into reporters and quantitatively determine whether it actually promotes -1 PRF (we typically use a cutoff level of ≥ 0.5% of a readthrough control), and whether it can function as an mRNA destabilizing element. Computational followup strategies include cross database referencing (e.g. assess- ing how -1 PRF in an mRNA or set of mRNAs might affect the transcriptome as monitored by microarray analysis), and phylogenetic analyses. In sum, the PRFdB provides yet another set of information for deep, one gene at a time mining, as well as for the broader approaches typified by the rapidly developing field of systematic biology. Discussion and conclusion With regard to future development, the PRFdb is currently processing the Xenopus laevis genome. The Arabidopsis thal- iana and Caenorabditis elegans genomes are currently in the queue, and additional genomes will be processed in the near future. In addition, the BLAST interface to the PRFdb has been used to discover Genbank sequences similar to the most statistically significant sequences in the data- base, thus providing a means to expand the PRFdb in a depth first manner. As more similar sequences are com- pleted, comparative genomics studies using sequence and/or mRNA structure alignments will be incorporated to enable identification of conserved -1 PRF signals across species and/or genes. As time progresses, additional com- putational and empirical information will allow for improved scoring, helping to increase the statistical rele- vance of the predicted secondary mRNA structures. These improvements will continue to make the PRFdb more useful and accessible to the research community, provid- ing a resource allowing individual users to identify -1 PRF signals in genes of interest, and as a metasource of infor- mation for cross referencing with other databases, e.g. genomes and DNA microarray databases. Availability and requirements The PRFdb is freely available on the web at http://dinman lab.umd.edu/prfdb and can be accessed though any standard web browser. Access and data downloading require no special requirements. RECODE: http://recode.genetics.utah.edu/ FSDB: http://wilab.inha.ac.kr/fsdb/ MLOGD: index.html http://guinevere.otago.ac.nz/aef/MLOGD/ Authors' contributions The original process, code, and webpage design was undertaken by JLJ. ATB played the primary role in improv- ing the original code, writing new code, improving the GUI and webpage design, and made significant contribu- tions to the preparation of the manuscript. NLH wrote the code to incorporate SNP data into the PRFdb, and also helped to streamline operation of the database. JDD con- ceived and directed the project, and wrote and prepared the bulk of the manuscript. All authors read and approved the final manuscript. Acknowledgements We would like to thank the National Cancer Institute for the generous use of their computing hardware, patience, and technical assistance. ATB was supported in part by a training grant from the NIH (T32 AI51967); NLH was supported in part by a grant to the University of Maryland from the Howard Hughes Medical Institute Undergraduate Science Education Pro- gram; JLJ was supported in part by fellowship to JLJ from the National Libraries of Medicine (F37 LM8333), and the project was supported by grants from the Public Health Service to JDD (R21 GM068123, R01 GM058859). References 1. Gesteland RF, Atkins JF: Recoding: Dynamic reprogramming of translation. Annu Rev Biochem 1996, 65:741-768. 2. Jacks T, Varmus HE: Expression of the Rous Sarcoma Virus pol gene by ribosomal frameshifting. Science 1985, 230:1237-1242. 3. Brierley I: Ribosomal frameshifting on viral RNAs. J Gen Virol 1995, 76:1885-1892. 4. Farabaugh PJ: Programmed translational frameshifting. 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