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Sci Rep ; 5: 12478, 2015 Jul 27.
Artigo em Inglês | MEDLINE | ID: mdl-26212482

RESUMO

Immunomodulatory oligodeoxynucleotides (IMODNs) are the short DNA sequences that activate the innate immune system via toll-like receptor 9. These sequences predominantly contain unmethylated CpG motifs. In this work, we describe VaccineDA (Vaccine DNA adjuvants), a web-based resource developed to design IMODN-based vaccine adjuvants. We collected and analyzed 2193 experimentally validated IMODNs obtained from the literature. Certain types of nucleotides (e.g., T, GT, TC, TT, CGT, TCG, TTT) are dominant in IMODNs. Based on these observations, we developed support vector machine-based models to predict IMODNs using various compositions. The developed models achieved the maximum Matthews Correlation Coefficient (MCC) of 0.75 with an accuracy of 87.57% using the pentanucleotide composition. The integration of motif information further improved the performance of our model from the MCC of 0.75 to 0.77. Similarly, models were developed to predict palindromic IMODNs and attained a maximum MCC of 0.84 with the accuracy of 91.94%. These models were evaluated using a five-fold cross-validation technique as well as validated on an independent dataset. The models developed in this study were integrated into VaccineDA to provide a wide range of services that facilitate the design of DNA-based vaccine adjuvants (http://crdd.osdd.net/raghava/vaccineda/).


Assuntos
Avaliação Pré-Clínica de Medicamentos/métodos , Software , Receptor Toll-Like 9/genética , Receptor Toll-Like 9/imunologia , Vacinas de DNA/genética , Vacinas de DNA/imunologia , Algoritmos , Sequência de Bases , Mapeamento Cromossômico/métodos , Desenho de Fármacos , Humanos , Internet , Dados de Sequência Molecular , Análise de Sequência de DNA/métodos
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