Ultraviolet Genomic Modeling
Ultraviolet genomic modeling is a method by which the ultraviolet sensitivity of microorganisms can be determined through evaluation of the complete microbial genome. Certain specific nucleic acid sequences have a high potential for dimerization under UV exposure, including the pyrimidine base doublets thymine-thymine (TT), thymine-cytosine (TC), cytosine-cytosine (CC). Purines flanked by pyrimidine doublets, of which there are eight, are also susceptible to dimerization. The dimerization of these sequences is also influenced by the surrounding bases and the permutations yield over one hundred sequences with varying dimerization potential. Base counting software is used to identify these sequences and the results are quantified as new bioinformatics parameters with genome-wide applications. A mathematical algorithm is used to compute a relative index of UV sensitivity for each microbe. Correlation of the genomic model with known ultraviolet susceptibilities of over 160 microbes has resulted in a general model that can be used to predict the UV sensitivities of bacteria, RNA viruses and DNA viruses based on their complete genomes. Since current UV bioassays are estimated to have an error range of +/-30%, the genomic model may form a benchmark by which the accuracy of bioassay testing may be gauged. An extensive list of predicted UV sensitivities is presented for microbes that do not currently have published UV susceptibilities, including many nosocomial and zoonotic pathogens and bioweapon agents. The model may also be used to interpret the effects of relative humidity on microbial susceptibility to UV exposure. Other applications of the model are discussed including the use of the genomic model to assess the survival of microbes in an airstream or water stream via PCR technology, since the model can predict the survival percentage based on DNA damage alone.
The susceptibility of viruses and bacteria to inactivation by ultraviolet light has long been a matter of great interest to the ultraviolet industries involved in disinfection of air, water, and surfaces. Since the early 1930s over 600 studies have been performed on microorganisms to evaluate their UV sensitivity (Kowalski 2009). Previously, the UV susceptibility of any microbe could only be assessed only by laboratory bioassays and the number of pathogens that have been evaluated in laboratories is a small fraction of the hundreds of pathogenic and allergenic microbes of concern. All the studies on UV inactivation that have been performed represent only about 235 different microbial species, but only about 120 of these species are relevant to human health. There are hundreds more human pathogens and allergens of concern that remain to be evaluated. Emergence of new diseases and new variants of old diseases (like SARS virus, MRSA, and H1N1 flu) often raise questions about the proper UV dosage for disinfection. With the ultraviolet genomic model, UV susceptibility can be predicted to an accuracy that may exceed that of traditional laboratory testing. This approach involves mathematical modeling of the complete genomes of microbes to determine their susceptibility to ultraviolet (UV) irradiation. Base-counting software and a specific methodology are used to establish the exact sequences of nucleic acid that are prone to UV photodimerization. The frequencies of occurrence of these potential dimers are computed and correlated with the ultraviolet susceptibility of viruses and bacteria. Accuracies of approximately 82-93% or better are achieved.
This method results in the definition of new bioinformatics parameters that may represent intrinsic properties of microbial species. Other useful applications of this novel method are possible, including PCR bioassays. A generalized model can also be formulated for UVA and UVB spectra, and is theorized for ionizing radiation. Possible applications in mutation research and cancer research are discussed. The UV susceptibility of any microbe is defined in terms of a UV inactivation rate constant, which is the logarithmic slope of population decay under UV exposure. A more commonly used parameter, the D90 value, is the UV dose for a 90% disinfection rate.
The ultraviolet genomic model consists of a methodology for reading the complete genome and identifying those base pairs that have a high potential for photodimerization. Photodimerization occurs when a UV photon is absorbed by a base and the base photoreacts with a neighboring base to produce a dimer. The dimer inhibits the normal DNA or RNA reproduction mechanism and thereby inactivates the microbe. The specific sequences that can result in photodimers include thymine-thymine (TT), thymine-cytosine (TC or CT), cytosine-cytosine (CC), and purine-pyrimidine dimers (TA, TG, CA, CG) that form under certain conditions. These photodimers have been the subject of much study over the years and much is known about their relevance to UV inactivation (Setlow 1966, Meistrich 1970, Lamola 1973, Unrau 1973, Patrick 1977). Becker and Wang (1989) provided results from PCR analysis showing the relative proportions of photoproducts produced by these particular dimers and suggested a general method for evaluating UV sensitivity in terms of these dimerization sites.
For more information on the subject of ultraviolet genomic modelling see the article downloads in Publications or access them below:
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A Genomic Model for the Prediction of Ultraviolet Inactivation Rate Constants for RNA and DNA Viruses Kowalski, W.J., Bahnfleth, W.P., Hernandez, M.T. (2009). IUVA Air Treatment Conference, Cambridge, MA, May 5. (pdf download).