Daniel M Weinberger | Search PubMed

PubMed2026

Genomic surveillance of a deeply sampled local population reveals age-specific drivers of RSV transmission.

Respiratory syncytial virus (RSV) disproportionately causes severe infections among infants and older adults, yet the key age group responsible for viral spread to other age groups remains poorly defined. While current immunization approaches effectively reduce disease severity among the most vulnerable, identifying the core drivers of infection is essential to effectively disrupt population-level transmission. By generating 910 whole-genome viral sequences of RSV from all age groups (<1 to 65+ years) in Connecticut, we identified that children aged 12-35 months are the primary drivers of viral transmission to other age groups. This group significantly shapes the genetic diversity of circulating strains. Furthermore, we found that RSV is introduced into the community through frequent and independent entries from other US regions throughout the year, rather than through a single explosive seasonal introduction or long-term local persistence. Ultimately, our findings justify prevention strategies that expand beyond reducing disease burden to actively prioritizing the reduction of transmission and infection.

Journal Article↗

PubMed2026

A tiled amplicon protocol for culture-free whole-genome sequencing of M. tuberculosis from clinical specimens.

Whole-genome sequencing of Mycobacterium tuberculosis can be a valuable tool for TB surveillance and treatment, providing insights into transmission patterns and comprehensive drug susceptibility testing. However, the slow growth of M. tuberculosis means traditional culture-based sequencing methods can take weeks to return results, which has limited the widespread adoption of these techniques and limited their use in clinical decision-making. Tiled amplicon sequencing is a fast, reliable, and cost-effective method of whole-genome sequencing that can be done directly on clinical specimens and has been implemented at scale in academic and public health laboratories across the world; it was the cornerstone of SARS-CoV-2 sequencing and has been adapted for a wide range of viral pathogens. However, similar methods are not yet available for far larger bacterial genomes. Extending this approach to M. tuberculosis would significantly reduce the cost, labor, and turnaround time for whole-genome sequencing. We designed a tiled amplicon panel consisting of 5,128 primers that covers the entire M. tuberculosis genome, the largest tiled amplicon sequencing panel we are aware of to date. Applying our amplicon panels to clinical samples of sputum, we show the ability to recover whole-genome bacterial sequences without the need for culture. The resulting sequence data can be used to determine M. tuberculosis lineage and reliably identify markers of drug resistance. Using this approach in clinical settings could reduce the time needed for comprehensive drug susceptibility testing from weeks to days and enable genomic epidemiology to be performed at scale, even in resource-limited settings.IMPORTANCEWe have developed and tested an amplicon panel, TB-seq, for the priority pathogen Mycobacterium tuberculosis, demonstrating recovery of near-full genomes directly from patient sputum, including mixed and low-concentration samples. This approach significantly reduces the turnaround time for this slow-growing bacterium while maintaining high accuracy in detecting clinically relevant mutations, including those associated with drug resistance. Given the global burden of tuberculosis and the critical need for faster diagnostic solutions, we believe our method has the potential to improve clinical decision-making and public health strategies.

Mycobacterium tuberculosis↗