Abstract
Histones are DNA-binding proteins found in the chromatin of all eukaryotic cells. They are highly conserved and can be grouped into five major classes: H1/H5, H2A, H2B, H3, and H4. Two copies of H2A, H2B, H3, and H4 bind to about 160 base pairs of DNA forming the core of the nucleosome (the repeating structure of chromatin) and H1/H5 bind to its DNA linker sequence. Overall, histones have a high arginine/lysine content that is optimal for interaction with DNA. This sequence bias can make the classification of histones difficult using standard sequence similarity approaches. Therefore, in this paper, we applied support vector machine (SVM) to recognize and classify histones on the basis of their amino acid and dipeptide composition. On evaluation through a five-fold cross-validation, the SVM-based method was able to distinguish histones from nonhistones (nuclear proteins) with an accuracy around 98%. Similarly, we obtained an overall >95% accuracy in discriminating the five classes of histones through the application of 1-versus-rest (1-v-r) SVM. Finally, we have applied this SVM-based method to the detection of histones from whole proteomes and found a comparable sensitivity to that accomplished by hidden Markov motifs (HMM) profiles.
Highlights
It has been more than 20 years since the discovery that HIV-1 is the cause of acquired immune deficiency syndrome (AIDS), we are not yet close to realizing a vaccine to halt the devastation created by the AIDS pandemic [1]
The present report supports the notion that T cell responses in HIV patients are impaired and argues for optimizing the composition of epitope-based vaccines using data obtained from naive individuals
Further experimental work shall include analysis of the T cell responses in naive and HIV-1-infected patients using in vitro stimulated CD8
Summary
It has been more than 20 years since the discovery that HIV-1 is the cause of acquired immune deficiency syndrome (AIDS), we are not yet close to realizing a vaccine to halt the devastation created by the AIDS pandemic [1]. HIV-1 clearance by the human host immune system and development of effective natural immunity have never been observed in AIDS patients. With up to a billion new viral particles produced per day in an infected individual, HIV-1 genetic variability can be greater within one host than the worldwide variability of influenza A virus in any year. This sequence/epitope variability thwarts effective cellular and humoral immune responses. HIV-1 is difficult to neutralize because the viral envelope glycoproteins are protected by a glycan shield, and exist in several distinct conformations, rendering conserved epitopes largely inaccessible to antibody-mediated neutralization [4]
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