Transcriptional ups and downs: patterns of gene expression in the life cycle of Toxoplasma gondii.

Toxoplasma gondii reproduces sexually in felines and asexually in virtually all warm-blooded animals, including humans. This obligate intracellular parasite alternates between biologically distinct developmental stages throughout its complex life cycle. Stage conversion is crucial for T. gondii transmission, persistence, and the maintenance of genetic diversity within the species. Genome-wide comparative transcriptomic studies have contributed invaluable insights into the regulatory gene networks underlying T. gondii development.

Computer-Assisted and Data Driven Approaches for Surveillance, Drug Discovery, and Vaccine Design for the Zika Virus.

Human life has been at the edge of catastrophe for millennia due diseases which emerge and reemerge at random. The recent outbreak of the Zika virus (ZIKV) is one such menace that shook the global public health community abruptly. Modern technologies, including computational tools as well as experimental approaches, need to be harnessed fast and effectively in a coordinated manner in order to properly address such challenges. In this paper, based on our earlier research, we have proposed a four-pronged approach to tackle the emerging pathogens like ZIKV: (a) Epidemiological modelling of spread mechanisms of ZIKV; (b) assessment of the public health risk of newly emerging strains of the pathogens by comparing them with existing strains/pathogens using fast computational sequence comparison methods; (c) implementation of vaccine design methods in order to produce a set of probable peptide vaccine candidates for quick synthesis/production and testing in the laboratory; and (d) designing of novel therapeutic molecules and their laboratory testing as well as validation of new drugs or repurposing of drugs for use against ZIKV. For each of these stages, we provide an extensive review of the technical challenges and current state-of-the-art. Further, we outline the future areas of research and discuss how they can work together to proactively combat ZIKV or future emerging pathogens.

Base Distribution in Dengue Nucleotide Sequences Differs Significantly from Other Mosquito-Borne Human-Infecting Flavivirus Members.

INTRODUCTION: Among the mosquito-borne human-infecting flavivirus species that include Zika, West Nile, yellow fever, Japanese encephalitis and Dengue viruses, the Zika virus is found to be closest to Dengue virus, sharing the same clade in the Flavivirus phylogenetic tree. We consider these five flaviviruses and on closer examination in our analyses, the nucleotide sequences of the Dengue viral genes (envelope and NS5) and genomes are seen to be quite widely different from the other four flaviviruses. We consider the extent of this distinction and determine the advantage and/or disadvantage such differences may confer upon the Dengue viral pathogenesis. METHODS: We have primarily used a 2D graphical representation technique to show the differences in base distributions in these five flaviviruses and subsequently, obtained quantitative estimates of the differences. Similarity/dissimilarity between the viruses based on the genes were also determined which showed that the differences with the Dengue genes are more pronounced. RESULTS: We found that the Dengue viruses compared to the other four flaviviruses spread rapidly worldwide and became endemic in various regions with small alterations in sequence composition relative to the host populations as revealed by codon usage biases and phylogenetic examination. CONCLUSION: We conclude that the Dengue genes are indeed more widely separated from the other aforementioned mosquito-borne human-infecting flaviviruses due to excess adenine component, a feature that is sparse in the literature. Such excesses have a bearing on drug and vaccine, especially peptide vaccine, development and should be considered appropriately.

Epidemics and Peptide Vaccine Response: A Brief Review.

We briefly review the situations arising out of epidemics that erupt rather suddenly, threatening life and livelihoods of humans. Ebola, Zika and the Nipah virus outbreaks are recent examples where the viral epidemics have led to considerably high degree of fatalities or debilitating consequences. The problems are accentuated by a lack of drugs or vaccines effective against the new and emergent viruses, and the inordinate amount of temporal and financial resources that are required to combat the novel pathogens. Progress in computational, biological and informational sciences have made it possible to consider design of synthetic vaccines that can be rapidly developed and deployed to help stem the damages. In this review, we consider the pros and cons of this new paradigm and suggest a new system where the manufacturing process can be decentralized to provide more targeted vaccines to meet the urgent needs of protection in case of a rampaging epidemic.

Graphical representation methods: How well do they discriminate between homologous gene sequences?

Graphical representation methods constitute a class of alignment-free techniques for comparative study of biomolecular sequences. In this brief commentary, we study how well some of these methods can discriminate among closely related genes.