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KHAN, MOHAMMAD ASİF

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MOHAMMAD ASİF

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KHAN

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2010 - 2019212020 - 20227
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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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    Correlation of host inflammatory cytokines and immune-related metabolites, but not viral NS1 protein, with disease severity of dengue virus infection
    (2020-08-01T00:00:00Z) Soe, Hui Jen; Manikam, Rishya; Raju, Chandramathi Samudi; Khan, MOHAMMAD ASİF; Sekaran, Shamala Devi; KHAN, MOHAMMAD ASİF
    Severe dengue can be lethal caused by manifestations such as severe bleeding, fluid accumulation and organ impairment. This study aimed to investigate the role of dengue non-structural 1 (NS1) protein and host factors contributing to severe dengue. Electrical cell-substrate impedance sensing system was used to investigate the changes in barrier function of microvascular endothelial cells treated NS1 protein and serum samples from patients with different disease severity. Cytokines and metabolites profiles were assessed using a multiplex cytokine assay and liquid chromatography mass spectrometry respectively. The findings showed that NS1 was able to induce the loss of barrier function in microvascular endothelium in a dose dependent manner, however, the level of NS1 in serum samples did not correlate with the extent of vascular leakage induced. Further assessment of host factors revealed that cytokines such as CCL2, CCL5, CCL20 and CXCL1, as well as adhesion molecule ICAM-1, that are involved in leukocytes infiltration were expressed higher in dengue patients in comparison to healthy individuals. In addition, metabolomics study revealed the presence of deregulated metabolites involved in the phospholipid metabolism pathway in patients with severe manifestations. In conclusion, disease severity in dengue virus infection did not correlate directly with NS1 level, but instead with host factors that are involved in the regulation of junctional integrity and phospholipid metabolism. However, as the studied population was relatively small in this study, these exploratory findings should be confirmed by expanding the sample size using an independent cohort to further establish the significance of this study.
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    Dissecting the Dynamics of HIV-1 Protein Sequence Diversity
    (2013-04-01T00:00:00Z) Hu, Yongli; Tan, Paul ThiamJoo; Tan, Tin Wee; August, J. Thomas; KHAN, MOHAMMAD ASİF; KHAN, MOHAMMAD ASİF
    The rapid mutation of human immunodeficiency virus-type 1 (HIV-1) and the limited characterization of the composition and incidence of the variant population are major obstacles to the development of an effective HIV-1 vaccine. This issue was addressed by a comprehensive analysis of over 58,000 clade B HIV-1 protein sequences reported over at least 26 years. The sequences were aligned and the 2,874 overlapping nonamer amino acid positions of the viral proteome, each a possible core binding domain for human leukocyte antigen molecules and T-cell receptors, were quantitatively analyzed for four patterns of sequence motifs: (1) -index-, the most prevalent sequence; (2) -major- variant, the most common variant sequence; (3) -minor- variants, multiple different sequences, each with an incidence less than that of the major variant; and (4) -unique- variants, each observed only once in the alignment. The collective incidence of the major, minor, and unique variants at each nonamer position represented the total variant population for the position. Positions with more than 50% total variants contained correspondingly reduced incidences of index and major variant sequences and increased minor and unique variants. Highly diverse positions, with 80 to 98% variant nonamer sequences, were present in each protein, including 5% of Gag, and 27% of Env and Nef, each. The multitude of different variant nonamer sequences (i.e. nonatypes; up to 68%) at the highly diverse positions, represented by the major, multiple minor, and multiple unique variants likely supported variants function both in immune escape and as altered peptide ligands with deleterious T-cell responses. The patterns of mutational change were consistent with the sequences of individual HXB2 and C1P viruses and can be considered applicable to all HIV-1 viruses. This characterization of HIV-1 protein mutation provides a foundation for the design of peptide-based vaccines and therapeutics.
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    Advancing standards for bioinformatics activities: persistence, reproducibility, disambiguation and Minimum Information About a Bioinformatics investigation (MIABi)
    (2010-12-01T00:00:00Z) Tan, Tin Wee; Tong, Joo Chuan; KHAN, MOHAMMAD ASİF; de Silva, Mark; Lim, Kuan Siong; Ranganathan, Shoba; KHAN, MOHAMMAD ASİF
    The 2010 International Conference on Bioinformatics, InCoB2010, which is the annual conference of the Asia-Pacific Bioinformatics Network (APBioNet) has agreed to publish conference papers in compliance with the proposed Minimum Information about a Bioinformatics investigation (MIABi), proposed in June 2009. Authors of the conference supplements in BMC Bioinformatics, BMC Genomics and Immunome Research have consented to cooperate in this process, which will include the procedures described herein, where appropriate, to ensure data and software persistence and perpetuity, database and resource re-instantiability and reproducibility of results, author and contributor identity disambiguation and MIABi-compliance. Wherever possible, datasets and databases will be submitted to depositories with standardized terminologies. As standards are evolving, this process is intended as a prelude to the 100 BioDatabases (BioDB100) initiative whereby APBioNet collaborators will contribute exemplar databases to demonstrate the feasibility of standards-compliance and participate in refining the process for peer-review of such publications and validation of scientific claims and standards compliance. This testbed represents another step in advancing standards-based processes in the bioinformatics community which is essential to the growing interoperability of biological data, information, knowledge and computational resources.
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    Editorial: Bioinformatics and the Translation of Data-Driven Discoveries
    (2022-05-01T00:00:00Z) KHAN, MOHAMMAD ASİF; Ranganathan, Shoba; Suravajhala, Prashanth; KHAN, MOHAMMAD ASİF
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    Classification of Dengue Fever Patients Based on Gene Expression Data Using Support Vector Machines
    (2010-06-01T00:00:00Z) Gomes, Ana Lisa V.; Wee, Lawrence J. K.; KHAN, MOHAMMAD ASİF; Gil, Laura H. V. G.; Marques, Ernesto T. A.; Calzavara-Silva, Carlos E.; Tan, Tin Wee; KHAN, MOHAMMAD ASİF
    Background: Symptomatic infection by dengue virus (DENV) can range from dengue fever (DF) to dengue haemorrhagic fever (DHF), however, the determinants of DF or DHF progression are not completely understood. It is hypothesised that host innate immune response factors are involved in modulating the disease outcome and the expression levels of genes involved in this response could be used as early prognostic markers for disease severity.
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    Cheminformatics-Based Drug Design Approach for Identification of Inhibitors Targeting the Characteristic Residues of MMP-13 Hemopexin Domain
    (2010-08-01T00:00:00Z) Kothapalli, Roopa; KHAN, MOHAMMAD ASİF; Basappa, Basappa; Gopalsamy, Anupriya; Chong, Yap Seng; Annamalai, Loganath; KHAN, MOHAMMAD ASİF
    Background: MMP-13, a zinc dependent protease which catalyses the cleavage of type II collagen, is expressed in osteoarthritis (OA) and rheumatoid arthritis (RA) patients, but not in normal adult tissues. Therefore, the protease has been intensively studied as a target for the inhibition of progression of OA and RA. Recent reports suggest that selective inhibition of MMP-13 may be achieved by targeting the hemopexin (Hpx) domain of the protease, which is critical for substrate specificity. In this study, we applied a cheminformatics-based drug design approach for the identification and characterization of inhibitors targeting the amino acid residues characteristic to Hpx domain of MMP-13; these inhibitors may potentially be employed in the treatment of OA and RA.
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    Developing critical thinking inSTEMeducation through inquiry-based writing in the laboratory classroom
    (2021-01-01T00:00:00Z) Jeon, Ah-Jung; Kellogg, David; Khan, MOHAMMAD ASİF; Tucker-Kellogg, Greg; KHAN, MOHAMMAD ASİF
    Laboratory pedagogy is moving away from step-by-step instructions and toward inquiry-based learning, but only now developing methods for integrating inquiry-based writing (IBW) practices into the laboratory course. Based on an earlier proposal (Science 2011;332:919), we designed and implemented an IBW sequence in a university bioinformatics course. We automatically generated unique, double-blinded, biologically plausible DNA sequences for each student. After guided instruction, students investigated sequences independently and responded through IBW writing assignments. IBW assignments were structured as condensed versions of a scientific research article, and because the sequences were double blinded, they were also assessed as authentic science and evaluated on clarity and persuasiveness. We piloted the approach in a seven-day workshop (35 students) at Perdana University in Malaysia. We observed dramatically improved student engagement and indirect evidence of improved learning outcomes over a similar workshop without IBW. Based on student feedback, initial discomfort with the writing component abated in favor of an overall positive response and increasing comfort with the high demands of student writing. Similarly, encouraging results were found in a semester length undergraduate module at the National University of Singapore (155 students).
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    Identification of Conserved and HLA Promiscuous DENV3 T-Cell Epitopes
    (2013-10-01T00:00:00Z) Nascimento, Eduardo J. M.; Mailliard, Robbie B.; KHAN, MOHAMMAD ASİF; Sidney, John; Sette, Alessandro; Guzman, Nicole; Paulaitis, Michael; de Melo, Andrea Barbosa; Cordeiro, Marli T.; Gil, Laura V. G.; Lemonnier, Francoir; Rinaldo, Charles; August, J. Thomas; Marques, Ernesto T. A.; KHAN, MOHAMMAD ASİF
    Anti-dengue T-cell responses have been implicated in both protection and immunopathology. However, most of the T-cell studies for dengue include few epitopes, with limited knowledge of their inter-serotype variation and the breadth of their human leukocyte antigen (HLA) affinity. In order to expand our knowledge of HLA-restricted dengue epitopes, we screened T-cell responses against 477 overlapping peptides derived from structural and non-structural proteins of the dengue virus serotype 3 (DENV3) by use of HLA class I and II transgenic mice (TgM): A2, A24, B7, DR2, DR3 and DR4. TgM were inoculated with peptides pools and the T-cell immunogenic peptides were identified by ELISPOT. Nine HLA class I and 97 HLA class II novel DENV3 epitopes were identified based on immunogenicity in TgM and their HLA affinity was further confirmed by binding assays analysis. A subset of these epitopes activated memory T-cells from DENV3 immune volunteers and was also capable of priming naive T-cells, ex vivo, from dengue IgG negative individuals. Analysis of inter-and intra-serotype variation of such an epitope (A02-restricted) allowed us to identify altered peptide ligands not only in DENV3 but also in other DENV serotypes. These studies also characterized the HLA promiscuity of 23 HLA class II epitopes bearing highly conserved sequences, six of which could bind to more than 10 different HLA molecules representing a large percentage of the global population. These epitope data are invaluable to investigate the role of T-cells in dengue immunity/pathogenesis and vaccine design.
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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.