(@digenoma) — bluesky.baby

New method out! RFhap combines multiple k-mer lengths + ML to bin long reads in trio data. Result: ~3× fewer long switch errors, while keeping contiguity and consensus quality intact.

31.01.2026 10:48 👍 1 🔁 0 💬 0 📌 0

Ultra-deep sequencing reveals intra-host diversity and co-infection-driven evolution of SARS-CoV-2 As COVID-19 enters an endemic phase, SARS-CoV-2 continues to diversify under ongoing immune pressure, with Omicron sublineages and episodic emergent variants sustaining reinfections worldwide. Intra-host evolution represents the earliest stage of this diversification, yet remains undercharacterized, particularly in regions with limited genomic surveillance. Here, we conducted high-throughput sequencing on 96 nasopharyngeal swab samples from Chilean individuals (2020-2022), achieving an average per-base genome coverage of ~60,000x across the viral genome. This ultra-deep sequencing coverage enabled the identification of intra-host single-nucleotide variants (iSNVs) and co-infection events with high sensitivity and accuracy. Co-infections, especially with Omicron, significantly increased iSNV frequency and recombination, driving viral diversity. Evolutionary analysis based on the non-synonymous to synonymous ratio (dN/dS) shows that Omicron is under extensive purifying selection (global dN/dS ~ 0.55). However, Omicron co-infection cases exhibited higher dN/dS ratios (~0.58), suggesting a lower level of purifying selection and increased genetic diversity. Notably, the Spike gene showed dN/dS ratios indicative of positive selection (dN/dS > 1), which are more pronounced in co-infection cases than in Omicron alone. This suggests that co-infections are providing the substrate for the emergence of new variants with enhanced transmissibility and immune evasion capabilities. Together, these findings demonstrate that ultra-deep sequencing is crucial for mapping the evolutionary forces driving SARS-CoV-2 intra-host adaptation and the emergence of new variants. ### Competing Interest Statement The authors have declared no competing interest. Agencia Nacional de Investigación y Desarrollo, https://ror.org/02ap3w078, 1221029

Universidad de O’Higgins scientists sequenced 96 COVID-19 samples in Chile and found that co-infections with multiple variants, especially Omicron, led to higher within-host viral diversity and signs of adaptive evolution that may spark new variants.

www.biorxiv.org/content/10.6...

20.01.2026 02:41 👍 5 🔁 1 💬 0 📌 0

Happy to share this COVID history that born as an error of sequencing depth! doi.org/10.64898/202...

20.01.2026 14:51 👍 1 🔁 0 💬 0 📌 0

Kmc3

20.01.2026 10:29 👍 4 🔁 0 💬 1 📌 0

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