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Better understanding of viral genomics and virus-host interactions can lead to a better understanding of viral diseases. RNA viruses exist as genetically diverse populations; their ability to rapidly adapt helps to determine their diversity. In recent years, the danger of RNA viruses been demonstrated with several examples of emerging or re-emerging diseases. With rapid urbanization, globalization, and increasing human populations, the possibility of a pandemic outbreak is a serious threat.Recently, a new method of RNA circularization was developed to help overcome the challenge of error rates in next generation sequencing. This method, one of the most powerful in our platform, is called CirSeq.

CirSeq can also be used for other areas of study that require precise determination of low-frequency mutations, such as cancer genomics. A cancer can be considered a population of semi-independent cells that are evolving under selection pressure within the patient’s body, akin to a population of viruses evolving under selection pressure within a host’s body. Understanding the mutations underlying the reproductive and survival advantages of cancer cells, compared with noncancerous cells, could lead to enhanced possibilities for personalized medicine, including subtype-specific treatment options. In addition to cancer and virology, CirSeq can be useful in the study of aging and other infectious diseases. Greater sensitivity to detect low frequency mutations can be used to develop predictive biomarkers for early detection, “liquid biopsies” (assessment of genetic material shed from tumors in a blood sample), and detailed “mutation landscapes” for the study of pathogenesis and cellular populations.

Analysis of Virus Genome and Host Regulation Data

Host-Pathogen Circuitry

Host-pathogen circuitry refers to a complex network of interactions between viral strains that have a major effect on viral evolution. The high rate of mutation for RNA viruses, natural selection in the context of viral survival and reproduction in the host is in part responsible for such pandemic outbreaks as bird flu, Ebola, Dengue and most recently, the Zika virus. Our objective is to identify key players in the network of dependencies between virus and host as well as select reliable points of intervention where this process can be stopped.

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CirSeq: Precision Sequencing

Human pathogens, particularly viruses, exert important impacts on the human population in terms of morbidity and mortality. A better understanding of viral genomics and virus-host interactions via sequencing technologies can allow for a better understanding of viral diseases. Computational biological methods are steadily improving. Our platform provides computational big data analysis tools and solutions that allow researchers to take advantage of unprecedented opportunities in diagnostics, therapeutics, and vaccine research.

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Virology Studies on T-BioInfo

Genome-wide fitness calculations enabled by CirSeq, combined with structural information, can provide high-definition, bias-free insights into structure-function relationships, potentially revealing novel functions for viral proteins and RNA structures, as well as nuanced insights into a viral genome’s phenotypic space. Such analyses have the power to reveal protein residues or domains that directly correspond to viral functional plasticity and may significantly inform our structural and mechanistic understanding of host–pathogen interactions.

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In light of ongoing research using CirSeq, computational approaches have been implemented as parts of the T-BioInfo Platform. The platform offers a visual and intuitive interface to connect algorithms into pipelines, making the computational approach more user friendly. The virology pipeline on T-BioInfo integrates visualization as an output, allowing researchers to see their data in a clear and meaningful way. The use of visualization allows for identification of significant biological insights without overwhelming the user with informatics complexities that are not necessary for a biologist to understand.

See the link below for a more detailed description of Pine Biotech’s vision for virology research using CirSeq and the T-BioInfo platform.

Mutation “Fitness” as Key to Interrupting Viral Adaptation and Other Uses of CirSeq Data Analysis

For an interactive demo of the output, you can view this link: http://www.pine-biotech.com/viz/views/poliotest.html

Working with Pine Biotech has been an immense pleasure thanks to their willingness to provide great tutorials and a platform which allows us to truly understand how to best analyze our big data sets. We are certain as Pine Biotech continues to develop new algorithms for varied areas of analysis we will be able to find novel insights relevant to disease states in the future.

Cecilia Sanchez
Tulane University