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Fig 1.

Study design.

The flowchart summarizes the steps followed to identify viral content in the human blood DNA from whole-genome sequencing reads.

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Fig 2.

Viral content.

The heatmap shows the presence of reads of viral nature in sequencing reactions of blood from 8,240 individuals. Extensive phage and other viral DNA is found in sequencing reactions, but it is almost universally associated to including phiX174 phage spike-in in the reaction (used in 60% of samples). For reference, we include the ubiquitous identification of human endogenous retrovirus (HERVs) sequences in the pool of unmapped reads.

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Fig 3.

Prevalence and abundance of human DNA viruses and retroviruses in 8,240 individuals.

A. Frequency of 19 human viruses in the study population ranked according to their prevalence. B. The viral load of human viruses represented on the x-axis as genome copies per 100,000 human cells; the bar represents the median.

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Table 1.

Detected human viruses in blood DNA of 8,240 individuals.

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Fig 4.

Genome coverage of selected human viruses.

Shown are the alignment of reads contributed by all individuals carrying the corresponding virus. The depth of coverage (y-axis) changes in scale as a reflection of the viral abundance and prevalence. Gaps in coverage (e.g., in EBV) generally reflect repetitive regions that are masked during data processing.

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Fig 5.

Integration of human herpesvirus 6.

The two populations of HHV6A andHHV6B are present in a bimodal distribution. The frequency of integrated viruses, at approximately 0.5 per cell corresponds to the haploid nature of the integration in the case of inherited, vertical transmission—from one of the parents. The identification of chimeric reads, or paired human-virus reads is shown for a substantial proportion of integrated HHV6 (green dots). The bar represents the median.

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Fig 6.

Relative proportion and viral load in the context of age, sex and ancestry.

The relative proportion, normalized to 100% for visualization purposes (A, C and E) and distribution of observed viral loads (B, D and F) are depicted for the 8 viruses that have the largest prevalence in the study. Among the 4,505 with demographic information, the ancestries were: EUR, European = 3,048; AFR, African = 665; MDE, Middle Eastern = 94; EAS, East Asian = 91; CSA, Central South Asian = 54; AMR, Admixed American = 8; Multi-Racial and Others = 545.

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