Diagnostics have proven to be crucial to the COVID-19 pandemic response. There are three major methods for the detection of SARS-CoV-2 infection and their role has evolved during the course of the ...pandemic. Molecular tests such as PCR are highly sensitive and specific at detecting viral RNA, and are recommended by WHO for confirming diagnosis in individuals who are symptomatic and for activating public health measures. Antigen rapid detection tests detect viral proteins and, although they are less sensitive than molecular tests, have the advantages of being easier to do, giving a faster time to result, of being lower cost, and able to detect infection in those who are most likely to be at risk of transmitting the virus to others. Antigen rapid detection tests can be used as a public health tool for screening individuals at enhanced risk of infection, to protect people who are clinically vulnerable, to ensure safe travel and the resumption of schooling and social activities, and to enable economic recovery. With vaccine roll-out, antibody tests (which detect the host's response to infection or vaccination) can be useful surveillance tools to inform public policy, but should not be used to provide proof of immunity, as the correlates of protection remain unclear. All three types of COVID-19 test continue to have a crucial role in the transition from pandemic response to pandemic control.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
Global health inequities: more challenges, some solutions Tangcharoensathien, Viroj; Lekagul, Angkana; Teo, Yik-Ying
Bulletin of the World Health Organization,
2024-Feb-01, 2024-02-01, 20240201, Volume:
102, Issue:
2
Journal Article
Peer reviewed
Open access
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CEKLJ, DOBA, IZUM, KILJ, NUK, ODKLJ, OILJ, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK, VSZLJ
SpoTyping is a fast and accurate program for in silico spoligotyping of Mycobacterium tuberculosis isolates from next-generation sequencing reads. This novel method achieves high accuracy for reads ...of both uniform and varying lengths, and is about 20 to 40 times faster than SpolPred. SpoTyping also integrates the function of producing a report summarizing associated epidemiological data from a global database of all isolates having the same spoligotype. SpoTyping is freely available at: https://github.com/xiaeryu/SpoTyping-v2.0 .
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IZUM, KILJ, NUK, PILJ, PNG, SAZU, UL, UM, UPUK
The COVID-19 pandemic is an unprecedented global crisis. Many countries have implemented restrictions on population movement to slow the spread of severe acute respiratory syndrome coronavirus 2 and ...prevent health systems from becoming overwhelmed; some have instituted full or partial lockdowns. However, lockdowns and other extreme restrictions cannot be sustained for the long term in the hope that there will be an effective vaccine or treatment for COVID-19. Governments worldwide now face the common challenge of easing lockdowns and restrictions while balancing various health, social, and economic concerns. To facilitate cross-country learning, this Health Policy paper uses an adapted framework to examine the approaches taken by nine high-income countries and regions that have started to ease COVID-19 restrictions: five in the Asia Pacific region (ie, Hong Kong Special Administrative Region, Japan, New Zealand, Singapore, and South Korea) and four in Europe (ie, Germany, Norway, Spain, and the UK). This comparative analysis presents important lessons to be learnt from the experiences of these countries and regions. Although the future of the virus is unknown at present, countries should continue to share their experiences, shield populations who are at risk, and suppress transmission to save lives.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
It is possible to predict whether a tuberculosis (TB) patient will fail to respond to specific antibiotics by sequencing the genome of the infecting Mycobacterium tuberculosis (Mtb) and observing ...whether the pathogen carries specific mutations at drug-resistance sites. This advancement has led to the collation of TB databases such as PATRIC and ReSeqTB that possess both whole genome sequences and drug resistance phenotypes of infecting Mtb isolates. Bioinformatics tools have also been developed to predict drug resistance from whole genome sequencing (WGS) data. Here, we evaluate the performance of four popular tools (TBProfiler, MyKrobe, KvarQ, PhyResSE) with 6746 isolates compiled from publicly available databases, and subsequently identify highly probable phenotyping errors in the databases by genetically predicting the drug phenotypes using all four software.
Our results show that these bioinformatics tools generally perform well in predicting the resistance status for two key first-line agents (isoniazid, rifampicin), but the accuracy is lower for second-line injectables and fluoroquinolones. The error rates in the databases are also non-trivial, reaching as high as 31.1% for prothionamide, and that phenotypes from ReSeqTB are more susceptible to errors.
The good performance of the automated software for drug resistance prediction from TB WGS data shown in this study further substantiates the usefulness and promise of utilising genetic data to accurately profile TB drug resistance, thereby reducing misdiagnoses arising from error-prone culture-based drug susceptibility testing.
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DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Statistics is an integral part of research in ophthalmology. The application of appropriate statistical strategies allows clinicians to realize the full potential in analyzing data from paired ocular ...measurements, longitudinal design, and genome-wide association study (GWAS). The increasing popularity of longitudinal follow-up in either clinical or epidemiologic study demands advanced statistical methodologies. This article describes robust statistical models that can cope with correlated components for both paired-eye data and repeated measurements over time. Also highlight are the statistical challenges and corresponding strategies available for testing multiple hypotheses with paired-eye data in GWAS, which has been the subject of intense interest for the past 5 years within the ophthalmology community in investigating the genetic etiology of eye disorders.
Medical research in Africa has yet to benefit from the advent of genome-wide association (GWA) analysis, partly because the genotyping tools and statistical methods that have been developed for ...European and Asian populations struggle to deal with the high levels of genome diversity and population structure in Africa. However, the haplotypic diversity of African populations might help to overcome one of the major roadblocks in GWA research, the fine mapping of causal variants. We review the methodological challenges and consider how GWA studies in Africa will be transformed by new approaches in statistical imputation and large-scale genome sequencing.
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DOBA, IJS, IZUM, KILJ, NUK, PILJ, PNG, SAZU, UILJ, UKNU, UL, UM, UPUK
Whole-genome sequencing (WGS) is now routinely used for the detection and identification of genetic variants, particularly single nucleotide polymorphisms (SNPs) in humans, and this has provided ...valuable new insights into human diversity, population histories and genetic association studies of traits and diseases. However, this relies on accurate detection and genotyping calling of the polymorphisms present in the samples sequenced. To minimize cost, the majority of current WGS studies, including the 1000 Genomes Project (1 KGP) have adopted low coverage sequencing of large number of samples, where such designs have inadvertently influenced the development of variant calling methods on WGS data. Assessment of variant accuracy are usually performed on the same set of low coverage individuals or a smaller number of deeply sequenced individuals. It is thus unclear how these variant calling methods would fare for a dataset of ∼100 samples from a population not part of the 1 KGP that have been sequenced at various coverage depths.
Using down-sampling of the sequencing reads obtained from the Singapore Sequencing Malay Project (SSMP), and a set of SNP calls from the same individuals genotyped on the Illumina Omni1-Quad array, we assessed the sensitivity of SNP detection, accuracy of genotype calls made and variant accuracy for six commonly used variant calling methods of GATK, SAMtools, Consensus Assessment of Sequence and Variation (CASAVA), VarScan, glfTools and SOAPsnp. The results indicate that at 5× coverage depth, the multi-sample callers of GATK and SAMtools yield the best accuracy particularly if the study samples are called together with a large number of individuals such as those from 1000 Genomes Project. If study samples are sequenced at a high coverage depth such as 30×, CASAVA has the highest variant accuracy as compared with the other variant callers assessed.
Despite extensive efforts to address it, the vastness of uncharacterized 'dark matter' microbial genetic diversity can impact short-read sequencing based metagenomic studies. Population-specific ...biases in genomic reference databases can further compound this problem. Leveraging advances in hybrid assembly (using short and long reads) and Hi-C technologies in a cross-sectional survey, we deeply characterized 109 gut microbiomes from three ethnicities in Singapore to comprehensively reconstruct 4497 medium and high-quality metagenome assembled genomes, 1708 of which were missing in short-read only analysis and with >28× N50 improvement. Species-level clustering identified 70 (>10% of total) novel gut species out of 685, improved reference genomes for 363 species (53% of total), and discovered 3413 strains unique to these populations. Among the top 10 most abundant gut bacteria in our study, one of the species and >80% of strains were unrepresented in existing databases. Annotation of biosynthetic gene clusters (BGCs) uncovered more than 27,000 BGCs with a large fraction (36-88%) unrepresented in current databases, and with several unique clusters predicted to produce bacteriocins that could significantly alter microbiome community structure. These results reveal significant uncharacterized gut microbial diversity in Southeast Asian populations and highlight the utility of hybrid metagenomic references for bioprospecting and disease-focused studies.
Polypoidal choroidal vasculopathy (PCV), a subtype of age-related macular degeneration (AMD) more frequently seen in East Asians, has both common and distinct clinical manifestations with typical ...neovascular AMD (tAMD). We aim to examine the extent to which common genetic variants are shared between these two subtypes. We performed the meta-analysis of association in a total of 1062 PCV patients, 1157 tAMD patients and 5275 controls of East Asian descent from the Genetics of AMD in Asians Consortium at the 34 known AMD loci. A total of eight loci were significantly associated with PCV, including age-related maculopathy susceptibility 2 (ARMS2)-HtrA serine peptidase 1 (HTRA1), complement factor H (CFH), C2-CFB-SKIV2L, CETP, VEGFA, ADAMTS9-AS2 and TGFBR1 (P<5 × 10
) from the single-nucleotide polymorphism-based test and COL4A3 from the gene-based tests (P
=2.02 × 10
). PCV and tAMD are genetically highly correlated (r
=0.69, P=4.68 × 10
), with AMD known loci accounting for up to 36% variation. Weaker association for PCV was observed at ARMS2-HTRA1 (P
=4.39 × 10
) and KMT2E-SRPK2(P
=4.43 × 10
), compared with tAMD. Variants at CFH, CETP and VEGFA exhibited different association signals in East Asians, in contrast to those in European individuals. Our data suggest a substantially shared genetic susceptibility for PCV and tAMD, while also highlight the unique associations for PCV, which is useful in understanding the pathogenesis of PCV.
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EMUNI, FIS, FZAB, GEOZS, GIS, IJS, IMTLJ, KILJ, KISLJ, MFDPS, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, SBMB, SBNM, UKNU, UL, UM, UPUK, VKSCE, ZAGLJ
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