Abstract
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/).
Highlights
The characteristics of the immunomodulatory oligodexoynucleotides to design efficient adjuvants
We identified features that can be used to discriminate between immunomodulatory oligonucleotides (IMODNs) and non-IMODNs
It was observed that the percent composition of thymine (T) in IMODNs (~30%) is significantly higher than that in non-IMODNs (~16%)
Summary
The characteristics of the immunomodulatory oligodexoynucleotides to design efficient adjuvants. We described a web-based resource built to aid in the design of oligonucleotides (ODNs)-based adjuvants. ODNs that stimulate the innate immunity are referred to as immunomodulatory oligonucleotides (IMODNs). ODNs that cannot activate the immune system are referred to as non-IMODNs. First, we collected experimentally well-characterized IMODNs from the literature, mainly from patents. We developed a web-based platform/resource referred to as VaccineDA (“Vaccine DNA Adjuvants”), which is freely available to the community at http://crdd. We developed a web-based platform/resource referred to as VaccineDA (“Vaccine DNA Adjuvants”), which is freely available to the community at http://crdd. osdd.net/raghava/vaccineda/
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