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Fulltext SVC obstruction and cardiac tamponade

Leong YK, Ong HS

Heart Asia, 2012;4(1):56.
PMID: 27326031 DOI: 10.1136/heartasia-2012-010101
Comparative Genome Sequence Analysis Reveals the Extent of Diversity and Conservation for Glycan-Associated Proteins in Burkholderia spp

Ong HS, Mohamed R, Firdaus-Raih M

Comp. Funct. Genomics, 2012;2012:752867.
PMID: 22991502

Members of the Burkholderia family occupy diverse ecological niches. In pathogenic family members, glycan-associated proteins are often linked to functions that include virulence, protein conformation maintenance, surface recognition, cell adhesion, and immune system evasion. Comparative analysis of available Burkholderia genomes has revealed a core set of 178 glycan-associated proteins shared by all Burkholderia of which 68 are homologous to known essential genes. The genome sequence comparisons revealed insights into species-specific gene acquisitions through gene transfers, identified an S-layer protein, and proposed that significantly reactive surface proteins are associated to sugar moieties as a potential means to circumvent host defense mechanisms. The comparative analysis using a curated database of search queries enabled us to gain insights into the extent of conservation and diversity, as well as the possible virulence-associated roles of glycan-associated proteins in members of the Burkholderia spp. The curated list of glycan-associated proteins used can also be directed to screen other genomes for glycan-associated homologs.
Fulltext A systematic bioinformatics approach for large-scale identification and characterization of host-pathogen shared sequences

James SA, Ong HS, Hari R, Khan AM

BMC Genomics, 2021 Sep 28;22(Suppl 3):700.
PMID: 34583643 DOI: 10.1186/s12864-021-07657-4

BACKGROUND: Biology has entered the era of big data with the advent of high-throughput omics technologies. Biological databases provide public access to petabytes of data and information facilitating knowledge discovery. Over the years, sequence data of pathogens has seen a large increase in the number of records, given the relatively small genome size and their important role as infectious and symbiotic agents. Humans are host to numerous pathogenic diseases, such as that by viruses, many of which are responsible for high mortality and morbidity. The interaction between pathogens and humans over the evolutionary history has resulted in sharing of sequences, with important biological and evolutionary implications.
RESULTS: This study describes a large-scale, systematic bioinformatics approach for identification and characterization of shared sequences between the host and pathogen. An application of the approach is demonstrated through identification and characterization of the Flaviviridae-human share-ome. A total of 2430 nonamers represented the Flaviviridae-human share-ome with 100% identity. Although the share-ome represented a small fraction of the repertoire of Flaviviridae (~ 0.12%) and human (~ 0.013%) non-redundant nonamers, the 2430 shared nonamers mapped to 16,946 Flaviviridae and 7506 human non-redundant protein sequences. The shared nonamer sequences mapped to 125 species of Flaviviridae, including several with unclassified genus. The majority (~ 68%) of the shared sequences mapped to Hepacivirus C species; West Nile, dengue and Zika viruses of the Flavivirus genus accounted for ~ 11%, ~ 7%, and ~ 3%, respectively, of the Flaviviridae protein sequences (16,946) mapped by the share-ome. Further characterization of the share-ome provided important structural-functional insights to Flaviviridae-human interactions.
CONCLUSION: Mapping of the host-pathogen share-ome has important implications for the design of vaccines and drugs, diagnostics, disease surveillance and the discovery of unknown, potential host-pathogen interactions. The generic workflow presented herein is potentially applicable to a variety of pathogens, such as of viral, bacterial or parasitic origin.
Fulltext DNA tetrominoes: the construction of DNA nanostructures using self-organised heterogeneous deoxyribonucleic acids shapes

Ong HS, Rahim MS, Firdaus-Raih M, Ramlan EI

PLoS One, 2015;10(8):e0134520.
PMID: 26258940 DOI: 10.1371/journal.pone.0134520

The unique programmability of nucleic acids offers alternative in constructing excitable and functional nanostructures. This work introduces an autonomous protocol to construct DNA Tetris shapes (L-Shape, B-Shape, T-Shape and I-Shape) using modular DNA blocks. The protocol exploits the rich number of sequence combinations available from the nucleic acid alphabets, thus allowing for diversity to be applied in designing various DNA nanostructures. Instead of a deterministic set of sequences corresponding to a particular design, the protocol promotes a large pool of DNA shapes that can assemble to conform to any desired structures. By utilising evolutionary programming in the design stage, DNA blocks are subjected to processes such as sequence insertion, deletion and base shifting in order to enrich the diversity of the resulting shapes based on a set of cascading filters. The optimisation algorithm allows mutation to be exerted indefinitely on the candidate sequences until these sequences complied with all the four fitness criteria. Generated candidates from the protocol are in agreement with the filter cascades and thermodynamic simulation. Further validation using gel electrophoresis indicated the formation of the designed shapes. Thus, supporting the plausibility of constructing DNA nanostructures in a more hierarchical, modular, and interchangeable manner.
A reassessment of the higher-order factor structure of the German Schizotypal Personality Questionnaire (SPQ-G) in German-speaking adults

Barron D, Voracek M, Tran US, Ong HS, Morgan KD, Towell T, et al.

Psychiatry Res, 2018 11;269:328-336.
PMID: 30173038 DOI: 10.1016/j.psychres.2018.08.070

The Schizotypal Personality Questionnaire (SPQ) is a widely-used self-report instrument for the assessment of schizotypal personality traits. However, the factor structure of scores on English and non-English translations of the SPQ has been a matter of debate. With little previous factorial evaluation of the German version of the SPQ (SPQ-G), we re-assessed the higher-order factor structure of the measure. A total of 2,428 German-speaking adults from Central Europe (CE) and the United Kingdom (UK) completed the SPQ-G. Confirmatory factor analysis - testing proposed 2-, 3-, and 4-factor models of SPQ-G scores - indicated that the 4-factor solution had best fit. Partial measurement invariance across cultural group (CE and UK) and sex was obtained for the 4-factor model. Further analyses showed CE participants had significantly higher scores than UK participants on one schizotypal facet. These results suggest that scores on the SPQ-G are best explained in terms of a higher-order, 4-factor solution in German migrant and non-migrant adults.
Fulltext Advancing Personalized Medicine Through the Application of Whole Exome Sequencing and Big Data Analytics

Suwinski P, Ong C, Ling MHT, Poh YM, Khan AM, Ong HS

Front Genet, 2019;10:49.
PMID: 30809243 DOI: 10.3389/fgene.2019.00049

There is a growing attention toward personalized medicine. This is led by a fundamental shift from the 'one size fits all' paradigm for treatment of patients with conditions or predisposition to diseases, to one that embraces novel approaches, such as tailored target therapies, to achieve the best possible outcomes. Driven by these, several national and international genome projects have been initiated to reap the benefits of personalized medicine. Exome and targeted sequencing provide a balance between cost and benefit, in contrast to whole genome sequencing (WGS). Whole exome sequencing (WES) targets approximately 3% of the whole genome, which is the basis for protein-coding genes. Nonetheless, it has the characteristics of big data in large deployment. Herein, the application of WES and its relevance in advancing personalized medicine is reviewed. WES is mapped to Big Data "10 Vs" and the resulting challenges discussed. Application of existing biological databases and bioinformatics tools to address the bottleneck in data processing and analysis are presented, including the need for new generation big data analytics for the multi-omics challenges of personalized medicine. This includes the incorporation of artificial intelligence (AI) in the clinical utility landscape of genomic information, and future consideration to create a new frontier toward advancing the field of personalized medicine.
Self-assembly programming of DNA polyominoes

Ong HS, Syafiq-Rahim M, Kasim NH, Firdaus-Raih M, Ramlan EI

J Biotechnol, 2016 Oct 20;236:141-51.
PMID: 27569553 DOI: 10.1016/j.jbiotec.2016.08.017

Fabrication of functional DNA nanostructures operating at a cellular level has been accomplished through molecular programming techniques such as DNA origami and single-stranded tiles (SST). During implementation, restrictive and constraint dependent designs are enforced to ensure conformity is attainable. We propose a concept of DNA polyominoes that promotes flexibility in molecular programming. The fabrication of complex structures is achieved through self-assembly of distinct heterogeneous shapes (i.e., self-organised optimisation among competing DNA basic shapes) with total flexibility during the design and assembly phases. In this study, the plausibility of the approach is validated using the formation of multiple 3×4 DNA network fabricated from five basic DNA shapes with distinct configurations (monomino, tromino and tetrominoes). Computational tools to aid the design of compatible DNA shapes and the structure assembly assessment are presented. The formations of the desired structures were validated using Atomic Force Microscopy (AFM) imagery. Five 3×4 DNA networks were successfully constructed using combinatorics of these five distinct DNA heterogeneous shapes. Our findings revealed that the construction of DNA supra-structures could be achieved using a more natural-like orchestration as compared to the rigid and restrictive conventional approaches adopted previously.
Fulltext Moderate mitral regurgitation in association with ventricular septal defect in children: Does it warrant mitral valve repair?

Ong HS, Krishnasamy S, Rajandram R, Amirthalingam A, Yusof TNT, Sivalingam S

Ann Pediatr Cardiol, 2024;17(4):264-271.
PMID: 39698423 DOI: 10.4103/apc.apc_110_24

BACKGROUND: The management of ventricular septal defect (VSD) alongside mitral regurgitation (MR) in pediatric patients remains a contentious issue due to the intricacies of cardiac surgery and the need to minimize ischemic time. Despite observations of MR regression following VSD closure, definitive guidelines for this patient subset are lacking, particularly concerning the management of the subgroup of patients with moderate MR. The objective of the study is to explore the factors influencing the choice between surgical intervention and conservative management for the mitral valve (MV) in VSD patients with moderate MR.
MATERIALS AND METHODS: A retrospective cohort study from January 2000 to December 2015, we analyzed management trends and focused on 53 patients with both VSD and moderate MR. This cohort was subdivided into four groups: first by their MV pathology, and then stratified by the receipt of intervention towards the diseased MV. Our primary goal was to identify correlations, especially concerning surgical outcomes such as mortality and need for re-operation. Statistical significance is determined when the P value is lower than 0.05.
RESULTS: There were no notable differences in preoperative variables across four cohort groups, apart from the cross-clamp duration which was longest in Group B intervention. Outcome analysis showed survival rates that were higher in cohort groups that underwent intervention toward the disease MV regardless of existing MV morphology, although results were not statistically significant. Cox model analysis found no correlation between the cohort groups and postoperative outcomes, but cross-clamp duration significantly correlated with mortality.
CONCLUSIONS: In cases of VSD with moderate MR with associated pathologies of the valvular apparatus, opting for MV repair (MVr) appears to improve survival outcomes without significantly increasing postoperative morbidity. Similarly, for patients with moderate MR and isolated annular dilatation, surgical MVr is observed to have better survival trend compared to the control group.