Publications by authors named "Fransiskus Xaverius Ivan"

7 Publications

  • Page 1 of 1

Integrative microbiomics in bronchiectasis exacerbations.

Nat Med 2021 04 5;27(4):688-699. Epub 2021 Apr 5.

Lee Kong Chian School of Medicine, Nanyang Technological University, Singapore, Singapore.

Bronchiectasis, a progressive chronic airway disease, is characterized by microbial colonization and infection. We present an approach to the multi-biome that integrates bacterial, viral and fungal communities in bronchiectasis through weighted similarity network fusion ( https://integrative-microbiomics.ntu.edu.sg ). Patients at greatest risk of exacerbation have less complex microbial co-occurrence networks, reduced diversity and a higher degree of antagonistic interactions in their airway microbiome. Furthermore, longitudinal interactome dynamics reveals microbial antagonism during exacerbation, which resolves following treatment in an otherwise stable multi-biome. Assessment of the Pseudomonas interactome shows that interaction networks, rather than abundance alone, are associated with exacerbation risk, and that incorporation of microbial interaction data improves clinical prediction models. Shotgun metagenomic sequencing of an independent cohort validated the multi-biome interactions detected in targeted analysis and confirmed the association with exacerbation. Integrative microbiomics captures microbial interactions to determine exacerbation risk, which cannot be appreciated by the study of a single microbial group. Antibiotic strategies probably target the interaction networks rather than individual microbes, providing a fresh approach to the understanding of respiratory infection.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1038/s41591-021-01289-7DOI Listing
April 2021

The Healthy Airway Mycobiome in Individuals of Asian Descent.

Chest 2021 Feb 11;159(2):544-548. Epub 2020 Sep 11.

Lee Kong Chian School of Medicine, Nanyang Technological University, Singapore. Electronic address:

View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.chest.2020.09.072DOI Listing
February 2021

Environmental fungal sensitisation associates with poorer clinical outcomes in COPD.

Eur Respir J 2020 08 27;56(2). Epub 2020 Aug 27.

Lee Kong Chian School of Medicine, Nanyang Technological University, Singapore

Introduction: Allergic sensitisation to fungi such as are associated to poor clinical outcomes in asthma, bronchiectasis and cystic fibrosis; however, clinical relevance in COPD remains unclear.

Methods: Patients with stable COPD (n=446) and nondiseased controls (n=51) were prospectively recruited across three countries (Singapore, Malaysia and Hong Kong) and screened against a comprehensive allergen panel including house dust mites, pollens, cockroach and fungi. For the first time, using a metagenomics approach, we assessed outdoor and indoor environmental allergen exposure in COPD. We identified key fungi in outdoor air and developed specific-IgE assays against the top culturable fungi, linking sensitisation responses to COPD outcomes. Indoor air and surface allergens were prospectively evaluated by metagenomics in the homes of 11 COPD patients and linked to clinical outcome.

Results: High frequencies of sensitisation to a broad range of allergens occur in COPD. Fungal sensitisation associates with frequent exacerbations, and unsupervised clustering reveals a "highly sensitised fungal predominant" subgroup demonstrating significant symptomatology, frequent exacerbations and poor lung function. Outdoor and indoor environments serve as important reservoirs of fungal allergen exposure in COPD and promote a sensitisation response to outdoor air fungi. Indoor (home) environments with high fungal allergens associate with greater COPD symptoms and poorer lung function, illustrating the importance of environmental exposures on clinical outcomes in COPD.

Conclusion: Fungal sensitisation is prevalent in COPD and associates with frequent exacerbations representing a potential treatable trait. Outdoor and indoor (home) environments represent a key source of fungal allergen exposure, amenable to intervention, in "sensitised" COPD.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1183/13993003.00418-2020DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7453645PMC
August 2020

Structure-based discovery of novel inhibitors of Mycobacterium tuberculosis CYP121 from Indonesian natural products.

Comput Biol Chem 2020 Apr 17;85:107205. Epub 2020 Jan 17.

Faculty of Biology, Universitas Nasional, Jakarta, 12520, Indonesia.

Tuberculosis (TB) continues to be a serious global health threat with the emergence of multidrug-resistant tuberculosis (MDR-TB) and extremely drug-resistant tuberculosis (XDR-TB). There is an urgent need to discover new drugs to deal with the advent of drug-resistant TB variants. This study aims to find new M. tuberculosis CYP121 inhibitors by the screening of Indonesian natural products using the principle of structure-based drug design and discovery. In this work, eight natural compounds isolated from Rhoeo spathacea and Pluchea indica were selected based on their antimycobacterial activity. Derivatives compound were virtually designed from these natural molecules to improve the interaction of ligands with CYP121. Virtual screening of ligands was carried out using AutoDock Vina followed by 50 ns molecular dynamics simulation using YASARA to study the inhibition mechanism of the ligands. Two ligands, i.e., kaempferol (KAE) and its benzyl derivative (KAE3), are identified as the best CYP121 inhibitors based on their binding affinities and adherence to the Lipinski's rule. Results of molecular dynamics simulation indicate that KAE and KAE3 possess a unique inhibitory mechanism against CYP121 that is different from GGJ (control ligand). The control ligand alters the overall dynamics of the receptor, which is indicated by changes in residue flexibility away from CYP121 binding site. Meanwhile, the dynamic changes caused by the binding of KAE and KAE3 are isolated around the binding site of CYP121. These ligands can be developed for further potential biological activities.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.compbiolchem.2020.107205DOI Listing
April 2020

Rule-based meta-analysis reveals the major role of PB2 in influencing influenza A virus virulence in mice.

BMC Genomics 2019 Dec 24;20(Suppl 9):973. Epub 2019 Dec 24.

Biomedical Informatics Lab, School of Computer Science and Engineering, Nanyang Technological University, Singapore, Singapore.

Background: Influenza A virus (IAV) poses threats to human health and life. Many individual studies have been carried out in mice to uncover the viral factors responsible for the virulence of IAV infections. Nonetheless, a single study may not provide enough confident about virulence factors, hence combining several studies for a meta-analysis is desired to provide better views. For this, we documented more than 500 records of IAV infections in mice, whose viral proteins could be retrieved and the mouse lethal dose 50 or alternatively, weight loss and/or survival data, was/were available for virulence classification.

Results: IAV virulence models were learned from various datasets containing aligned IAV proteins and the corresponding two virulence classes (avirulent and virulent) or three virulence classes (low, intermediate and high virulence). Three proven rule-based learning approaches, i.e., OneR, JRip and PART, and additionally random forest were used for modelling. PART models achieved the best performance, with moderate average model accuracies ranged from 65.0 to 84.4% and from 54.0 to 66.6% for the two-class and three-class problems, respectively. PART models were comparable to or even better than random forest models and should be preferred based on the Occam's razor principle. Interestingly, the average accuracy of the models was improved when host information was taken into account. For model interpretation, we observed that although many sites in HA were highly correlated with virulence, PART models based on sites in PB2 could compete against and were often better than PART models based on sites in HA. Moreover, PART had a high preference to include sites in PB2 when models were learned from datasets containing the concatenated alignments of all IAV proteins. Several sites with a known contribution to virulence were found as the top protein sites, and site pairs that may synergistically influence virulence were also uncovered.

Conclusion: Modelling IAV virulence is a challenging problem. Rule-based models generated using viral proteins are useful for its advantage in interpretation, but only achieve moderate performance. Development of more advanced approaches that learn models from features extracted from both viral and host proteins shall be considered for future works.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1186/s12864-019-6295-8DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6929465PMC
December 2019

Peptide-Based Subunit Vaccine Design of T- and B-Cells Multi-Epitopes against Zika Virus Using Immunoinformatics Approaches.

Microorganisms 2019 Jul 31;7(8). Epub 2019 Jul 31.

Faculty of Biology, Universitas Nasional, Jakarta 12520, Indonesia.

The Zika virus disease, also known as Zika fever is an arboviral disease that became epidemic in the Pacific Islands and had spread to 18 territories of the Americas in 2016. Zika virus disease has been linked to several health problems such as microcephaly and the Guillain-Barré syndrome, but to date, there has been no vaccine available for Zika. Problems related to the development of a vaccine include the vaccination target, which covers pregnant women and children, and the antibody dependent enhancement (ADE), which can be caused by non-neutralizing antibodies. The peptide vaccine was chosen as a focus of this study as a safer platform to develop the Zika vaccine. In this study, a collection of Zika proteomes was used to find the best candidates for T- and B-cell epitopes using the immunoinformatics approach. The most promising T-cell epitopes were mapped using the selected human leukocyte antigen (HLA) alleles, and further molecular docking and dynamics studies showed a good peptide-HLA interaction for the best major histocompatibility complex-II (MHC-II) epitope. The most promising B-cell epitopes include four linear peptides predicted to be cross-reactive with T-cells, and conformational epitopes from two proteins accessible by antibodies in their native biological assembly. It is believed that the use of immunoinformatics methods is a promising strategy against the Zika viral infection in designing an efficacious multiepitope vaccine.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.3390/microorganisms7080226DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6722788PMC
July 2019

Computational analysis of the receptor binding specificity of novel influenza A/H7N9 viruses.

BMC Genomics 2018 May 9;19(Suppl 2):88. Epub 2018 May 9.

School of Computer Science and Engineering, Nanyang Technological University, Singapore, 639798, Singapore.

Background: Influenza viruses are undergoing continuous and rapid evolution. The fatal influenza A/H7N9 has drawn attention since the first wave of infections in March 2013, and raised more grave concerns with its increased potential to spread among humans. Experimental studies have revealed several host and virulence markers, indicating differential host binding preferences which can help estimate the potential of causing a pandemic. Here we systematically investigate the sequence pattern and structural characteristics of novel influenza A/H7N9 using computational approaches.

Results: The sequence analysis highlighted mutations in protein functional domains of influenza viruses. Molecular docking and molecular dynamics simulation revealed that the hemagglutinin (HA) of A/Taiwan/1/2017(H7N9) strain enhanced the binding with both avian and human receptor analogs, compared with the previous A/Shanghai/02/2013(H7N9) strain. The Molecular Mechanics - Poisson Boltzmann Surface Area (MM-PBSA) calculation revealed the change of residue-ligand interaction energy and detected the residues with conspicuous binding preference.

Conclusion: The results are novel and specific to the emerging influenza A/Taiwan/1/2017(H7N9) strain compared with A/Shanghai/02/2013(H7N9). Its enhanced ability to bind human receptor analogs, which are abundant in the human upper respiratory tract, may be responsible for the recent outbreak. Residues showing binding preference were detected, which could facilitate monitoring the circulating influenza viruses.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1186/s12864-018-4461-zDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5954268PMC
May 2018
-->