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Abstract Cytochrome P450 2D6 (CYP2D6) plays a crucial role in metabolizing approximately 20% of medications prescribed clinically. This enzyme is encoded by the CYP2D6 gene, known for its extensive polymorphism with over 170 catalogued haplotypes or star alleles, which can have a profound impact on drug efficacy and safety. Despite its importance, a gap exists in the global genomic databases, which are predominantly representative of European ancestries, thereby limiting comprehensive knowledge of CYP2D6 variation in ethnically diverse populations. In an effort to bridge this knowledge gap, we focused on elucidating the CYP2D6 variation landscape within a multi-ethnic Asian cohort, encompassing individuals of Chinese, Malay, and Indian descent. Our study comprised data analysis of 1850 whole genomes from the SG10K_Health dataset using an in-house consensus algorithm, which integrates the capabilities of Cyrius, Aldy, and StellarPGx. This analysis unveiled distinct population-specific star-allele distribution trends, highlighting the unique genetic makeup of the Singaporean population. Significantly, 46% of our cohort harbored actionable CYP2D6 variants—those with direct implications for drug dosing and treatment strategies. Furthermore, we identified 14 potential novel CYP2D6 star-alleles, of which 7 were observed in multiple individuals, suggesting their broader relevance. Overall, our study contributes novel data on CYP2D6 genetic variations specific to the Southeast Asian context. The findings are instrumental for the advancement of pharmacogenomics and personalized medicine, not only in Southeast Asia but also in other regions with comparable genetic diversity.

Abstract Hypervariable region sequencing of the 16S ribosomal RNA (rRNA) gene plays a critical role in microbial ecology by offering insights into bacterial communities within specific niches. While providing valuable genus-level information, its reliance on data from targeted genetic regions limits its overall utility. Recent advances in sequencing technologies have enabled characterisation of the full-length 16S rRNA gene, enhancing species-level classification. Although current short-read platforms are cost-effective and precise, they lack full-length 16S rRNA amplicon sequencing capability. This study aimed to evaluate the feasibility of a modified 150 bp paired-end full-length 16S rRNA amplicon short-read sequencing technique on the Illumina iSeq 100 and 16S rRNA amplicon assembly workflow by utilising a standard mock microbial community and subsequently performing exploratory characterisation of captive (zoo) and free-ranging African elephant (Loxodonta africana) respiratory microbiota. Our findings demonstrate that, despite generating assembled amplicons averaging 869 bp in length, this sequencing technique provides taxonomic assignments consistent with the theoretical composition of the mock community and respiratory microbiota of other mammals. Tentative bacterial signatures, potentially representing distinct respiratory tract compartments (trunk and lower respiratory tract) were visually identified, necessitating further investigation to gain deeper insights into their implication for elephant physiology and health.

Introduction: Investigating variation in genes involved in the absorption, distribution, metabolism, and excretion (ADME) of drugs are key to characterizing pharmacogenomic (PGx) relationships. ADME gene variation is relatively well characterized in European and Asian populations, but data from African populations are under-studied—which has implications for drug safety and effective use in Africa.Results: We identified significant ADME gene variation in African populations using data from 458 high-coverage whole genome sequences, 412 of which are novel, and from previously available African sequences from the 1,000 Genomes Project. ADME variation was not uniform across African populations, particularly within high impact coding variation. Copy number variation was detected in 116 ADME genes, with equal ratios of duplications/deletions. We identified 930 potential high impact coding variants, of which most are discrete to a single African population cluster. Large frequency differences (i.e., >10%) were seen in common high impact variants between clusters. Several novel variants are predicted to have a significant impact on protein structure, but additional functional work is needed to confirm the outcome of these for PGx use. Most variants of known clinical outcome are rare in Africa compared to European populations, potentially reflecting a clinical PGx research bias to European populations.Discussion: The genetic diversity of ADME genes across sub-Saharan African populations is large. The Southern African population cluster is most distinct from that of far West Africa. PGx strategies based on European variants will be of limited use in African populations. Although established variants are important, PGx must take into account the full range of African variation. This work urges further characterization of variants in African populations including in vitro and in silico studies, and to consider the unique African ADME landscape when developing precision medicine guidelines and tools for African populations.