Project description:<p>Definition of the human microbiome is an important scientific priority. This study will expand the scope of the investigation to include viruses, which account for a substantial proportion of infectious disease morbidity and mortality, especially in children. The long-term goal of this project is to describe the human virome in children and to investigate its relevance to febrile illnesses in children. The project will also seek to understand the relationship of the immune system to the composition of the virome. Thus, the project's specific aims are 1) To elucidate the spectrum of viruses that can be detected using non-biased, high throughput sequencing on samples of blood, respiratory, and gastrointestinal secretions from healthy children and to use this information as a basis for understanding the role of viruses in acute febrile illnesses without an obvious source, and 2) to investigate the effect of various forms of immunosuppression on the spectrum of viruses detected in children, and to use this information as a basis for understanding the role of viruses in acute febrile illnesses occurring in these children. Our preliminary studies show that diverse viruses can be detected in children having undiagnosed fever. To carry out the specific aims, well children will be enrolled prior to having elective surgery, and febrile otherwise well children will be enrolled from the Emergency Department at St. Louis Children's Hospital. Immunocompromised children will be recruited from hematopoietic stem cell and solid organ transplant clinics, the HIV/AIDS clinic, and the rheumatology/immunology clinic from the same hospital. Children with fever will have samples obtained at the time of the febrile illness and at 1 and 6-month follow-up visits. Selected samples from each study group will be analyzed at the Genome Center at Washington University (GCWU) using next generation 454 high throughput sequencing to detect and sequence all viral sequences present. We anticipate detecting and sequencing a broad range of viruses, including previously unrecognized agents. A variety of techniques will be used to investigate the significance of viruses detected. Virus-specific PCR assays will be used to determine the frequency and extent of viruses detected by sequencing, using the full range of samples collected. Host response to the detected viruses will be investigated using serologic analysis, cytokine profiling, and microarrays to characterize host gene expression. These studies will take advantage of follow-up samples to compare the acute response with the response in the convalescent period. This study will draw upon the expertise and technological assets of one of the world's most powerful sequencing centers to provide the research community with a comprehensive sequence data base of the viruses that are present in children, which can be used to improve our understanding of the causes of febrile illnesses in young children, many of which are currently undiagnosed.</p>

Project description:Spatial heterogeneity is a fundamental characteristic of organisms from viruses to humans. Measuring heterogeneity is challenging, especially for naked-eye invisible viruses, but of obvious importance. For example, spatial heterogeneity of virus distribution may strongly influence infection spreading and outbreaks in the case of pathogenic viruses; the spatial distribution (i.e., the inter-subject heterogeneity) of commensal viruses within/on our bodies can influence the competition, coexistence, and dispersal of viruses within or between our bodies. Taylor's power law (TPL) was first discovered in the 1960s to describe the spatial distributions of plant and/or animal populations, and since then it has been verified by numerous experimental and theoretical studies. Recently, TPL has been extended from population to community level and applied to bacterial communities. Here we report the first comprehensive testing of the TPL fitted to human virome datasets. It was found that the human virome follows the TPL as bacterial communities do. Furthermore, the TPL heterogeneity scaling parameter of human virome is virtually the same as that of the human bacterial microbiome (1.916 vs. 1.926). We postulate that the extreme closeness of human viruses and bacteria in heterogeneity scaling coefficients could be attributed to the fact that most of the viruses that were annotated in this study actually belong to bacteriophages (86% viral OTUs) that "piggyback" on their bacterial hosts, and their distributions are likely host-dependent. The scaling parameter, which measures the inter-subject heterogeneity changes, should be an innate property of human microbiomes including both bacteria and viruses. It is similar to the acceleration coefficient of the gravity (g = 9.8) as specified by Newton's law, which is invariant on the earth. Nevertheless, we caution that our postulation is contingent on an implicit assumption that the proportion of bacteriophages to total virome may not change significantly when more virus species can be identified in future.

Dataset Information

Sequence analysis of the human virome in febrile and afebrile children.

Publications

Sequence analysis of the human virome in febrile and afebrile children.

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