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- W3122060161 abstract "Background: Genomics have provided a wealth of knowledge into human and pathogen diversity that has been leveraged to reveal genetic associations to disease and susceptibility to infections. Pathogen diversity is used to trace the movement of disease-causing microbes and drug resistance. Ultradeep sequencing of pathogen genomes offers the opportunity to follow “clouds” of pathogen variants as they adapt to new environments within and between hosts using the statistical inference capacity of population genetics. CMV is a common herpesvirus and genetically the most complex viral pathogen of humans (∼235 kbp). Infections are lifelong, but generally asymptomatic in healthy individuals. However, CMV is a significant cause of morbidity and mortality in immune insufficient populations including those with acquired (e.g., HIV, transplant recipients) or genetic insufficiencies (e.g., SCID). Pregnant women also have a form of immune insufficiency. Each of these groups are at elevated risk of CMV reactivation or (re)infection. Methods and materials: We developed ultradeep sequencing and population genetic analytics for CMV infections. Archived, longitudinal CMV specimens from 6 immunosuppressed individuals and 13 congenitally infected infants were enriched for CMV genomic sequences and subjected to ultradeep, genome-wide sequencing. Data were then used to generate models of infection history based in population genetics. Results: In a collective comparison of different infections (congenital, transplant, SCID), effective population sizes (Ne) clustered with disease outcomes independent of the infection group. Ne is an estimation of the “parent” population size that generates progeny. Ne values segregated into 3 groups: resolved, ongoing, and asymptomatic infections. Analysis of longitudinal and compartmental specimens from congenitally infected infants revealed single or multiple “clouds” of viral sequences indicative of single or mixed CMV populations. Generation number estimates of clouds provided temporal distinctions between co-infections and reinfections (admixing). CMV reinfection is believed to be a significant issue related to congenital transmission as most women are latently infected with CMV a priori. Conclusion: Both Ne estimations and statistically robust demonstrations of reinfection demonstrate the value of ultradeep sequencing and population genetics in clinical settings. This approach provides a platform that should be adaptable to infections to pathogens in general." @default.
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- W3122060161 date "2020-12-01" @default.
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- W3122060161 title "Clinically relevant markers of infection revealed through population genetics: The example of cytomegalovirus infections" @default.
- W3122060161 doi "https://doi.org/10.1016/j.ijid.2020.09.1283" @default.
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