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KHAN, MOHAMMAD ASİF

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MOHAMMAD ASİF
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KHAN
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Start date: 2010 × End date: 2019 × Author: Khan, Asif M. ×

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Now showing 1 - 8 of 8
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    Advancing Personalized Medicine Through the Application of Whole Exome Sequencing and Big Data Analytics
    (2019-02-01T00:00:00Z) Suwinski, Pawel; Ong, ChuangKee; Ling, Maurice H. T.; Poh, Yang Ming; Khan, Asif M.; Ong, Hui San; KHAN, MOHAMMAD ASİF
    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.
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    Analysis of viral diversity for vaccine target discovery
    (2017-12-01T00:00:00Z) Khan, Asif M.; Hu, Yongli; Miotto, Olivo; Thevasagayam, Natascha M.; Sukumaran, Rashmi; Raman, Hadia Syahirah Abd; Brusic, Vladimir; Tan, Tin Wee; August, J. Thomas; KHAN, MOHAMMAD ASİF
    Background: Viral vaccine target discovery requires understanding the diversity of both the virus and the human immune system. The readily available and rapidly growing pool of viral sequence data in the public domain enable the identification and characterization of immune targets relevant to adaptive immunity. A systematic bioinformatics approach is necessary to facilitate the analysis of such large datasets for selection of potential candidate vaccine targets.
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    High dengue virus load differentially modulates human microvascular endothelial barrier function during early infection
    (2017-12-01T00:00:00Z) Soe, Hui Jen; Khan, Asif M.; Manikam, Rishya; Raju, Chandramathi Samudi; Vanhoutte, Paul; Sekaran, Shamala Devi; KHAN, MOHAMMAD ASİF
    Plasma leakage is the main pathophysiological feature in severe dengue, resulting from altered vascular barrier function associated with an inappropriate immune response triggered upon infection. The present study investigated functional changes using an electric cell-substrate impedance sensing system in four (brain, dermal, pulmonary and retinal) human microvascular endothelial cell (MEC) lines infected with purified dengue virus, followed by assessment of cytokine profiles and the expression of inter-endothelial junctional proteins. Modelling of changes in electrical impedance suggests that vascular leakage in dengue-infected MECs is mostly due to the modulation of cell-to-cell interactions, while this loss of vascular barrier function observed in the infected MECs varied between cell lines and DENV serotypes. High levels of inflammatory cytokines (IL-6 and TNF-alpha), chemokines (CXCL1, CXCL5, CXCL11, CX3CL1, CCL2 and CCL20) and adhesion molecules (VCAM-1) were differentially produced in the four infected MECs. Further, the tight junctional protein, ZO-1, was down-regulated in both the DENV-1-infected brain and pulmonary MECs, while claudin-1, PECAM-1 and VE-cadherin were differentially expressed in these two MECs after infection. Non-purified virus stock was also studied to investigate the impact of virus stock purity on dengue-specific immune responses, and the results suggest that virus stock propagated through cell culture may include factors that mask or alter the DENV-specific immune responses of the MECs. The findings of the present study show that high DENV load differentially modulates human microvascular endothelial barrier function and disrupts the function of inter-endothelial junctional proteins during early infection with organ-specific cytokine production.
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    STATdb: A Specialised Resource for the STATome
    (2014-08-01T00:00:00Z) Patro, C. Pawan K.; Khan, Asif M.; Tan, Tin Wee; Fu, Xin-Yuan; KHAN, MOHAMMAD ASİF
    Signal transducers and activators of transcription (STAT) proteins are key signalling molecules in metazoans, implicated in various cellular processes. Increased research in the field has resulted in the accumulation of STAT sequence and structure data, which are scattered across various public databases, missing extensive functional annotations, and prone to effort redundancy because of the dearth of community sharing. Therefore, there is a need to integrate the existing sequence, structure and functional data into a central repository, one that is enriched with annotations and provides a platform for community contributions. Herein, we present STATdb (publicly available at http://statdb.bic.nus.edu.sg/), the first integrated resource for STAT sequences comprising 1540 records representing the known STATome, enriched with existing structural and functional information from various databases and literature and including manual annotations. STATdb provides advanced features for data visualization, analysis and prediction, and community contributions. A key feature is a meta-predictor to characterise STAT sequences based on a novel classification that integrates STAT domain architecture, lineage and function. A curation policy workflow has been devised for regulated and structured community contributions, with an update policy for the seamless integration of new data and annotations.
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    Identification of highly conserved, serotype-specific dengue virus sequences: implications for vaccine design
    (2019-12-01T00:00:00Z) Chong, Li Chuin; Khan, Asif M.; KHAN, MOHAMMAD ASİF
    Background: The sequence diversity of dengue virus (DENV) is one of the challenges in developing an effective vaccine against the virus. Highly conserved, serotype-specific (HCSS), immune-relevant DENV sequences are attractive candidates for vaccine design, and represent an alternative to the approach of selecting pan-DENV conserved sequences. The former aims to limit the number of possible cross-reactive epitope variants in the population, while the latter aims to limit the cross-reactivity between the serotypes to favour a serotype-specific response. Herein, we performed a large-scale systematic study to map and characterise HCSS sequences in the DENV proteome.
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    Mapping HLA-A2,-A3 and-B7 supertype-restricted T-cell epitopes in the ebolavirus proteome
    (2018-01-01T00:00:00Z) Lim, Wan Ching; Khan, Asif M.; KHAN, MOHAMMAD ASİF
    Background: Ebolavirus (EBOV) is responsible for one of the most fatal diseases encountered by mankind. Cellular T-cell responses have been implicated to be important in providing protection against the virus. Antigenic variation can result in viral escape from immune recognition. Mapping targets of immune responses among the sequence of viral proteins is, thus, an important first step towards understanding the immune responses to viral variants and can aid in the identification of vaccine targets. Herein, we performed a large-scale, proteome-wide mapping and diversity analyses of putative HLA supertype-restricted T-cell epitopes of Zaire ebolavirus (ZEBOV), the most pathogenic species among the EBOV family.
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    African Trypanosome-Induced Blood-Brain Barrier Dysfunction under Shear Stress May Not Require ERK Activation
    (2015-03-01T00:00:00Z) Sumpio, Brandon J.; Chitragari, Gautham; Moriguchi, Takeshi; Shalaby, Sherif; Pappas-Brown, Valeria; Khan, Asif M.; Sekaran, Shamala Devi; Sumpio, Bauer E.; Grab, Dennis J.; KHAN, MOHAMMAD ASİF
    African trypanosomes are tsetse fly transmitted protozoan parasites responsible for human African trypanosomiasis, a disease characterized by a plethora of neurological symptoms and death. How the parasites under microvascular shear stress (SS) flow conditions in the brain cross the blood-brain barrier (BBB) is not known. In vitro studies using static models comprised of human brain microvascular endothelial cells (BMEC) show that BBB activation and crossing by trypanosomes requires the orchestration of parasite cysteine proteases and host calcium-mediated cell signaling. Here, we examine BMEC barrier function and the activation of extracellular signal-regulated kinase (ERK) 1/2 and ERK5, mitogen-activated protein kinase family regulators of microvascular permeability, under static and laminar SS flow and in the context of trypanosome infection. Confluent human BMEC were cultured in electric cell-substrate impedance sensing (ECIS) and parallel-plate glass slide chambers. The human BMEC were exposed to 2 or 14 dyn/cm(2) SS in the presence or absence of trypanosomes. Real-time changes in transendothelial electrical resistance (TEER) were monitored and phosphorylation of ERK1/2 and ERK5 analyzed by immunoblot assay. After reaching confluence under static conditions human BMEC TEER was found to rapidly increase when exposed to 2 dyn/cm2 SS, a condition that mimics SS in brain postcapillary venules. Addition of African trypanosomes caused a rapid drop in human BMEC TEER. Increasing SS to 14 dyn/cm2, a condition mimicking SS in brain capillaries, led to a transient increase in TEER in both control and infected human BMEC. However, no differences in ERK1/2 and ERK5 activation were found under any condition tested. African trypanosomiasis alters BBB permeability under low shear conditions through an ERK1/2 and ERK5 independent pathway.
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    g-FLUA2H: a web-based application to study the dynamics of animal-to-human mutation transmission for influenza viruses
    (2015-01-01T00:00:00Z) Sjaugi, Muhammad Farhan; Tan, Swan; Abd Raman, Hadia Syahirah; Lim, Wan Ching; Mohamed, Nik Elena Nik; August, J. Thomas; Khan, Asif M.; KHAN, MOHAMMAD ASİF
    g-FLUA2H is a web-based application focused on the analysis of the dynamics of influenza virus animal-to-human (A2H) mutation transmissions. The application only requires the viral protein sequences from both the animal and human host populations as input datasets. The comparative analyses between the co-aligned sequences of the two viral populations is based on a sliding window approach of size nine for statistical significance and data application to the major histocompatibility complex (MHC) and T-cell receptor (TCR) immune response mechanisms. The sequences at each of the aligned overlapping nonamer positions for the respective virus hosts are classified as four patterns of characteristic diversity motifs, as a basis for quantitative analyses: (i) -index-, the most prevalent sequence; (ii) -major- variant, the second most common sequence and the single most prevalent variant of the index, with at least one amino acid mutation; (iii) -minor- variants, multiple different sequences, each with an incidence (percent occurrence) less than that of the major variant; and (iv) -unique- variants, each with only one occurrence in the alignment. The diversity motifs and their incidences at each of the nonamer positions allow evaluation of the mutation transmission dynamics and selectivity of the viral sequences in relation to the animal and the human hosts. g-FLUA2H is facilitated by a grid back-end for parallel processing of large sequence datasets. The web-application is publicly available at http://bioinfo.perdanauniversity.edu.my/g-FLUA2H. It can be used for a detailed characterization of the composition and incidence of mutations present in the proteomes of influenza viruses from animal and human host populations, for a better understanding of host tropism.