Biology subjects

Barnes, K. G.

Publications and source records attributed to Barnes, K. G..

3 recordsLinked to original sources

bioRxiv2018

Capturing diverse microbial sequence with comprehensive and scalable probe design

Metagenomic sequencing has the potential to transform microbial detection and characteri zation, but new tools are needed to improve its sensitivity. We developed CATCH (Compact Aggregation of Targets for Comprehensive Hybridization), a computational method to enhance nucleic acid capture for enrichment of diverse microbial taxa. CATCH designs compact probe sets that achieve full coverage of known sequence diversity and that scale well with this diversity. To illustrate applications of CATCH, we focused on capturing viral genomes. We designed, synthesized, and validated multiple probe sets, including one that targets whole genomes of the 356 viral species known to infect humans. Capture with these probe sets enriched unique viral content on average 18x and allowed us to assemble genomes that we could not otherwise recover, while accurately preserving within-sample diversity. We used this approach to recover genomes from the 2018 Lassa fever outbreak in Nigeria and to improve detection of viral infections in samples with unknown content. Together, this work demonstrates a path toward more sensitive, cost-effective metagenomic sequencing.

genomics↗

bioRxiv2017

Genome sequencing reveals Zika virus diversity and spread in the Americas

Despite great attention given to the recent Zika virus (ZIKV) epidemic in the Americas, much remains unknown about its epidemiology and evolution, in part due to a lack of genomic data. We applied multiple sequencing approaches to generate 110 ZIKV genomes from clinical and mosquito samples from 10 countries and territories, greatly expanding the observed viral genetic diversity from this outbreak. We analyzed the timing and patterns of introductions into distinct geographic regions; our phylogenetic evidence suggests rapid expansion of the outbreak in Brazil and multiple introductions of outbreak strains into Puerto Rico, Honduras, Colombia, other Caribbean islands, and the continental US. We find that ZIKV circulated undetected in multiple regions for many months before the first locally transmitted cases were confirmed, highlighting the importance of viral surveillance. We identify mutations with possible functional implications for ZIKV biology and pathogenesis, as well as those potentially relevant to the effectiveness of diagnostic tests.

genomics↗

bioRxiv2017

Multiple introductions of Zika virus into the United States revealed through genomic epidemiology

Zika virus (ZIKV) is causing an unprecedented epidemic linked to severe congenital syndromes1,2. In July 2016, mosquito-borne ZIKV transmission was first reported in the continental United States and since then, hundreds of locally-acquired infections have been reported in Florida3. To gain insights into the timing, source, and likely route(s) of introduction of ZIKV into the continental United States, we tracked the virus from its first detection in Miami, Florida by direct sequencing of ZIKV genomes from infected patients and Aedes aegypti mosquitoes. We show that at least four distinct ZIKV introductions contributed to the outbreak in Florida and that local transmission likely started in the spring of 2016 - several months before its initial detection. By analyzing surveillance and genetic data, we discovered that ZIKV moved among transmission zones in Miami. Our analyses show that most introductions are phylogenetically linked to the Caribbean, a finding corroborated by the high incidence rates and traffic volumes from the region into the Miami area. By comparing mosquito abundance and travel flows, we describe the areas of southern Florida that are especially vulnerable to ZIKV introductions. Our study provides a deeper understanding of how ZIKV initiates and sustains transmission in new regions.

epidemiology↗