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Modern sequencing instruments bring unprecedented opportunity to study within-host viral evolution in conjunction with viral transmissions between hosts. However, no computational simulators are available to assist the characterization of within-host dynamics. This limits our ability to interpret epidemiological predictions incorporating within-host evolution and to validate computational inference tools. To fill this need we developed Apollo, a GPU-accelerated, out-of-core tool for within-host simulation of viral evolution and infection dynamics across population, tissue, and cellular levels. Apollo is scalable to hundreds of millions of viral genomes and can handle complex demographic and population genetic models. Apollo can replicate real within-host viral evolution; accurately recapturing observed viral sequences from an HIV cohort derived from initial population-genetic configurations. For practical applications, using Apollo-simulated viral genomes and transmission networks, we validated and uncovered the limitations of a widely used viral transmission inference tool.
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http://dx.doi.org/10.1101/2024.10.07.617101 | DOI Listing |
Nat Biotechnol
September 2025
European Molecular Biology Laboratory, European Bioinformatics Institute, Hinxton, UK.
The size of microbial sequence databases continues to grow beyond the abilities of existing alignment tools. We introduce LexicMap, a nucleotide sequence alignment tool for efficiently querying moderate-length sequences (>250 bp) such as a gene, plasmid or long read against up to millions of prokaryotic genomes. We construct a small set of probe k-mers, which are selected to efficiently sample the entire database to be indexed such that every 250-bp window of each database genome contains multiple seed k-mers, each with a shared prefix with one of the probes.
View Article and Find Full Text PDFInt J Biol Macromol
September 2025
School of Medicine, College of Medicine, National Cheng Kung University, Tainan, Taiwan. Electronic address:
The development of antiviral nanotherapeutics remains a formidable challenge due to the structural diversity and rapid evolution of viral surface glycoconjugates. Here, we report a rationally engineered multivalent Galectin-1 (Gal-1) nanoplatform based on 13-nm gold nanoparticles (AuNPs) for high-affinity glycan targeting and therapeutic inhibition of influenza virus. By leveraging site-specific conjugation and molecular orientation control, the AuNP/Gal-1 nanocomplex maximizes the exposure of carbohydrate recognition domains (CRDs) while preserving Gal-1's tertiary structure, as confirmed by molecular dynamics simulations and spectroscopic analyses.
View Article and Find Full Text PDFBiotechnol Adv
September 2025
Key Laboratory of Microbiological Metrology, Measurement & Bio-product Quality Security, State Administration for Market Regulation, China Jiliang University, Hangzhou 310018, China. Electronic address:
Nanopore direct RNA sequencing (DRS) is a transformative technology that enables full-length, single-molecule sequencing of native RNA, capturing transcript isoforms and preserving epitranscriptomic modifications without cDNA conversion. This review outlines key advances in DRS, including optimized protocols for mRNA, rRNA, tRNA, circRNA, and viral RNA, as well as analytical tools for isoform quantification, poly(A) tail measurement, fusion transcript identification, and base modification profiling. We highlight how DRS has redefined transcriptomic studies across diverse systems-from uncovering novel transcripts and alternative splicing events in cancer, plants, and parasites to enabling the direct detection of m6A, m5C, pseudouridine, and RNA editing events.
View Article and Find Full Text PDFSci Transl Med
September 2025
Vaccine Research Center (VRC), National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892, USA.
Human B cell immunity to the influenza hemagglutinin (HA) stem, a universal vaccine target, is often stereotyped and immunogenetically restricted, posing hurdles to study outside of humans. Here, we show that cynomolgus macaques vaccinated with an HA stem immunogen elicit humanlike public B cell lineages targeting two major conserved sites of vulnerability, the central stem and anchor epitopes. Central stem antibodies were predominantly derived from V1-138, the macaque homolog of human V1-69, a V gene preferentially used in human central stem broadly neutralizing antibodies (bnAbs).
View Article and Find Full Text PDFPLoS One
September 2025
Department of Ecology and Evolution, University of Chicago, Illinois, United States of America.
Kobuviruses (family Picornaviridae, genus Kobuvirus) are enteric viruses that infect a wide range of both human and animal hosts. Much of the evolutionary history of kobuviruses remains elusive, largely due to limited screening in wildlife. Bats have been implicated as major sources of virulent zoonoses, including coronaviruses, henipaviruses, lyssaviruses, and filoviruses, though much of the bat virome still remains uncharacterized.
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