Rationale for our approach.

<p>Rationale for our approach.</p

Presumed evolution of the <i>deltaretrovirus</i> pX region.

<p>The deltaretrovirus phylogeny is shown as a cladogram. Conventions are the same as in <a href="http://www.ploscompbiol.org/article/info:doi/10.1371/journal.pcbi.1003162#pcbi-1003162-g003" target="_blank">Figure 3</a>.</p

Analysis of the codon usage of overlapping frames from the benchmark dataset.

<p>Abbreviations are the same as in <a href="http://www.ploscompbiol.org/article/info:doi/10.1371/journal.pcbi.1003162#pcbi-1003162-t001" target="_blank">Table 1</a>. The last two overlaps have entered their genome by horizontal transfer (see text).</p><p><i>r_sA</i> is the Spearman rank correlation coefficient <i>r_s</i> between the codon usage of the ancestral frame and that of its genome. <i>r_sN</i> is the equivalent coefficient for the <i>de novo</i> frame. N_A and N_N are the number of codons on which <i>r_sA</i> and <i>r_sN</i> were calculated. The first row indicates whether calculations are presented for the actual overlapping frames or for the corresponding simulated frames. The calculation of P for the actual frames is based on Hotelling's t-test, whereas for simulated frames P is based on the distribution of the simulated <i>d₂₁</i> (see text). Agreement between t-Hotelling and simulation is calculated on the basis of whether corresponding P-values are both <0.05 or >0.05.</p

Prediction of the ancestral frame in overlapping genes from the benchmark dataset.

(1)<p>The last two overlaps have entered their genome by horizontal transfer and are not taken into account for calculations of specificity and sensitivity of the method.</p><p>Abbreviations and conventions are the same as in <a href="http://www.ploscompbiol.org/article/info:doi/10.1371/journal.pcbi.1003162#pcbi-1003162-t002" target="_blank">Table 2</a>. A frame is predicted ancestral if its <i>r_s</i> is positive and significantly higher than the <i>r_s</i> of the other frame (P<0.05, corresponding to t-Hotelling >1.70). If no prediction is possible, the field is left blank. Numerical values are the same as in <a href="http://www.ploscompbiol.org/article/info:doi/10.1371/journal.pcbi.1003162#pcbi-1003162-t003" target="_blank">Table 3</a> for actual frames, but are reproduced here for clarity.</p

Benchmark dataset of 27 overlapping genes with known genealogy.

(1)<p>gene overlaps described previously (see reference <a href="http://www.ploscompbiol.org/article/info:doi/10.1371/journal.pcbi.1003162#pcbi.1003162-Rancurel1" target="_blank">[3]</a>).</p>(2)<p>additional overlaps collected for this study.</p>(3)<p>The function is that of the overlapping region of the protein; if it is not known, the field is left blank.</p>(4)<p>The NS2 proteins of <i>brevidensoviruses</i> and that of <i>densoviruses</i> are not homologous (they are encoded in different frames relative to NS1).</p>(5)<p>The <i>alphacarmotetravirus</i> polymerase and <i>machlomovirus</i> capsid have originated by horizontal transfer and thus the two corresponding overlaps are not part of the benchmark dataset, although we perform the same analyses on them than on other overlaps(see text).</p><p>Abbreviations: AAP, assembly-activating protein; dsRNA, double-stranded RNA; C-term, C-terminal; L, large envelope protein; MP, movement protein; NABP, nucleic-acid binding protein; NS, non-structural protein; NSs, non-structural protein of the small RNA segment; N-term, N-terminal; Pog, predicted overlapping gene; Pol, Polymerase; SAT, small alternatively translated protein; ssDNA, single-stranded DNA; ssRNA, single-stranded RNA (+, positive or −, negative); TGBp2, Triple Gene Block protein 2; TGBp3, Triple Gene Block protein 3; VP, viral protein.</p

A genomic hotspot of origination of silencing suppressors in plus-strand RNA viruses.

<p>The replicases of <i>Nodaviridae</i> and <i>Bromoviridae</i> contain C-terminal extensions predicted disordered (thin boxes) downstream of their homologous polymerase (RdRP) domain. These extensions encode structurally unrelated suppressors of RNA silencing, B2 and 2b (PDB accession codes respectively 2AZ2 and 2ZI0) in different reading frames. Neither the C-terminal extensions nor the suppressors of RNA silencing have detectable sequence similarity, even between closely related genera. Which region is ancestral in each overlap could not be determined (see text).</p

A “gene nursery”: the pX region of <i>deltaretroviruses</i>.

<p>The pX region of HTLV1 encodes five genes unique to <i>deltaretroviruses</i> by a complex pattern of alternative splicing and leaky scanning <a href="http://www.ploscompbiol.org/article/info:doi/10.1371/journal.pcbi.1003162#pcbi.1003162-Gessain1" target="_blank">[36]</a>, <a href="http://www.ploscompbiol.org/article/info:doi/10.1371/journal.pcbi.1003162#pcbi.1003162-Baydoun1" target="_blank">[39]</a>. The initial exons of these genes are very short and have not been represented, nor have been shorter versions of p12 and p30 expressed alternatively. Only the 3′ end of the Env gene is represented. The figure is approximately to scale. Ancestral regions in red and <i>de novo</i> regions in blue. Frame numbering is as in <a href="http://www.ploscompbiol.org/article/info:doi/10.1371/journal.pcbi.1003162#pcbi.1003162-Firth2" target="_blank">[45]</a>, with the Tax frame taken as “0”. Protein regions with unusually low sequence complexity are indicated by dashed, grey lines.</p

Prediction, by codon usage, of the ancestral frame in overlapping reading frames with identical phylogenetic distribution.

<p>Conventions are the same as in <a href="http://www.ploscompbiol.org/article/info:doi/10.1371/journal.pcbi.1003162#pcbi-1003162-t003" target="_blank">Table 3</a>. A frame is predicted ancestral if its <i>r_s</i> is positive and significantly higher than the <i>r_s</i> of the other frame (P<0.05, corresponding to t-Hotelling>1.70).</p

Data_Sheet_1_On the impact of mass screening for SARS-CoV-2 through self-testing in Greece.PDF

BackgroundScreening programs that pre-emptively and routinely test population groups for disease at a massive scale were first implemented during the COVID-19 pandemic in a handful of countries. One of these countries was Greece, which implemented a mass self-testing program during 2021. In contrast to most other non-pharmaceutical interventions (NPIs), mass self-testing programs are particularly attractive for their relatively small financial and social burden, and it is therefore important to understand their effectiveness to inform policy makers and public health officials responding to future pandemics. This study aimed to estimate the number of deaths and hospitalizations averted by the program implemented in Greece and evaluate the impact of several operational decisions.MethodsGranular data from the mass self-testing program deployed by the Greek government between April and December 2021 were obtained. The data were used to fit a novel compartmental model that was developed to describe the dynamics of the COVID-19 pandemic in Greece in the presence of self-testing. The fitted model provided estimates on the effectiveness of the program in averting deaths and hospitalizations. Sensitivity analyses were used to evaluate the impact of operational decisions, including the scale of the program, targeting of sub-populations, and sensitivity (i.e., true positive rate) of tests.ResultsConservative estimates show that the program reduced the reproduction number by 4%, hospitalizations by 25%, and deaths by 20%, translating into approximately 20,000 averted hospitalizations and 2,000 averted deaths in Greece between April and December 2021.ConclusionMass self-testing programs are efficient NPIs with minimal social and financial burden; therefore, they are invaluable tools to be considered in pandemic preparedness and response.</p

Age distribution of ERVs by class.

<p>Age distribution of ERVs by class.</p