Biology subjects

Chew, Y. T.

Publications and source records attributed to Chew, Y. T..

3 recordsLinked to original sources

bioRxiv2026

Tracking two decades of global dengue virus lineage dynamics

Dengue virus (DENV) is genetically diverse, consisting of four antigenically distinct serotypes and extensive sub-serotype variation that can influence epidemiology and control. As DENV continues to expand globally, there is an urgent need to characterize the dynamics of distinct DENV genetic lineages, including their persistence, establishment, and spread. Using a standardized DENV lineage nomenclature system and 37,828 publicly available DENV genomes sampled from 2000-2024, we classified sequences across nine global regions to construct a comprehensive resource of regional lineage distributions over time. We found marked regional differences in lineage diversity, with higher lineage richness in Southeast and East Asia than in the Americas. We further showed that COVID-19-related disruptions were associated with decreased regional lineage persistence and detection of new lineages during 2020-2021, followed by rebounds after 2022 and, in some regions, substantial lineage turnover. Finally, we identified a small set of globally expansive (cosmopolitan) lineages that are over-represented in available sequences, including five first-order minor lineages detected in at least seven of nine regions: 3III_B.3, 2II_F.1, 2II_A.1, 1III_A.3, and 1I_K.3. Together, these results demonstrate how standardized lineage classification enables global tracking of emerging DENV diversity and supports targeted genomic surveillance.

bioinformatics↗

bioRxiv2025

The global phylogeography of rapidly expanding multidrug resistant Ural lineage 4.2 Mycobacterium tuberculosis

Multidrug resistant tuberculosis (MDR-TB) is a leading global health challenge. Recent studies identified a reproductively fit Ural lineage 4.2 MDR M. tuberculosis (Mtb) variant circulating within the Republic of Moldova. We searched a large publicly available dataset of [~]200,000 Mtb whole genome sequences and identified a clade of 1604 drug-resistant Mtb sequences harboring conserved resistance-conferring mutations that are closely related to the MDR Mtb variant circulating in Moldova. We identified the Russian Federation as the most likely country of origin for this clade, and we inferred several independent migration events from Russia and Moldova to other former Soviet Republics and several European countries. Using local branching index, we found that this clade is expanding more rapidly than comparable clades of lineage 4.2. This evolutionarily successful strains presence beyond Moldova poses a threat to MDR-TB control, and enhanced surveillance is necessary to reduce the risk of MDR-TB epidemics in the region. FundingThe authors report funding from the National Institutes of Health (R01AI180209, P01AI159402)

microbiology↗

bioRxiv2020

Precise and programmable C:G to G:C base editing in genomic DNA

Many genetic diseases are caused by single-nucleotide polymorphisms (SNPs). Base editors can correct SNPs at single-nucleotide resolution, but until recently, only allowed for C:G to T:A and A:T to G:C transition edits, addressing four out of twelve possible DNA base substitutions. Here we developed a novel class of C:G to G:C Base Editors (CGBEs) to create single-base genomic transversions in human cells. Our CGBEs consist of a nickase CRISPR-Cas9 (nCas9) fused to a cytosine deaminase and base excision repair (BER) proteins. Characterization of >30 CGBE candidates and 27 guide RNAs (gRNAs) revealed that CGBEs predominantly perform C:G to G:C editing (up to 90% purity), with rAPOBEC-nCas9-rXRCC1 being the most efficient (mean C:G to G:C edits at 15% and up to 37%). CGBEs target cytosine in WCW, ACC or GCT sequence contexts and within a precise two-nucleotide window of the target protospacer. We further targeted genes linked to dyslipidemia, hypertrophic cardiomyopathy, and deafness, showing the therapeutic potential of CGBE in interrogating and correcting human genetic diseases.

synthetic biology↗