Phenotypic and genotypic predictors forHIV/SIV tropism are available. The genotypic predictors are more rational. However, they are sequence alignment dependent only. Regrettably, non-homologous proteins are found to display common biological functionality. This indicates that sequence-dependent predictors cannot be trusted with appropriate classification of the HIV and SIV isolates, especially if the isolates belong to same tropic group but share divergent sequence alignment. There is therefore need for genotypic predictors that will incorporate embedded intrinsic biological characteristics of the HIV and SIV isolates in the determination of HIV tropism. Secondly, more than 30 positions with at least single mutation outside the V3 domain have been found to influence HIV Tropism. Disappointingly, the available sequence alignment-based HIV genotypic predictors engage only the hyper-variable region (V3) of the HIV gp120. This has resulted in inaccurate classification of HIV and SIV strains. Finally, available HIV genotypic predictors are found to lack the ability to identify and accurately evaluate the sequences of most HIV-1 non B clades, HIV-2 and SIV. Against this background, the ability of the Digital Signal Processing (DSP) Technique called Informational Spectrum Method (ISM), which does not engage sequence similarity but the embedded bio-functionalities of the entire gp120 sequence length to predict HIV and SIV tropism is therefore investigated. 83 isolates of HIV and SIV are subjected to ISM and three other procedures. Results are generated and findings correlated. For isolates, which are analyzable by the four procedures, the results from ISM and three other procedures are found to correlate. Using 50% affinity for the host CD4 as the cut-off, the tropism of the uncategorized isolates are predicted. ISM-based technique is adjudged a better procedure. It analyzes the sequences of all HIV (HIV-1 together with non B, and HIV-2) as well as SIV isolates including those that could not be investigated by other genotypic predictors. It engages the embedded biological characteristics rather than sequence similarity and utilizes the entire HIV gp120 sequence-length instead of V3 domain. This makes ISM-based procedure a better tool for over 180,000 isolates of HIV-1, HIV-2 and SIV in the UNIPROT database. Clinical approaches are unfeasible. This study recommends ISM technique principally for viral tropism prediction as it does not discriminate against HIV/SIVcategories. It suggests that further work be done to determine a suitable cut-off (as in geno2pheno[CORECEPTOR]), and the procedure in combination with other genotypic predictors be engaged in developing an algorithm for determining viral tropism.
Published in | Computational Biology and Bioinformatics (Volume 3, Issue 2) |
DOI | 10.11648/j.cbb.20150302.11 |
Page(s) | 21-30 |
Creative Commons |
This is an Open Access article, distributed under the terms of the Creative Commons Attribution 4.0 International License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution and reproduction in any medium or format, provided the original work is properly cited. |
Copyright |
Copyright © The Author(s), 2015. Published by Science Publishing Group |
CD4, Charge Rule, Digital Signal Processing, Geno2pheno, Genotypic, HIV/AIDS, HIV Surface Protein, Informational Spectrum Method, Phenotypic, Position-Specific Scoring Matrix
[1] | Adamson C and Freed E, “Novel approaches to inhibiting HIV-1 replication” Antiviral Research vol. 85(2010) pp. 119-141, 2010. |
[2] | Doms R W, “Beyond receptor expression: the influence of receptor conformation, density, and affinity in HIV-1 infection”,Virology, vol. 276(2) pp. 229-237, 2000. |
[3] | Berger E A, Murphy P M, Farber J M, “Chemokine receptors as HIV-1 co-receptors: roles in entry, tropism, and disease”, Annu. Rev. Immunol., vol. 17, pp. 657-700, 1999. |
[4] | Lusso P, “HIV and the chemokine system: 10 years later”, The EMBO Journal, vol. 25, pp. 447-456, 2006. |
[5] | Berger E R, Doms E, Fenyo B, Korber D, et al, “A new classification for HIV-1”, Nature, vol. 391, p. 240, 1998. |
[6] | Doranz BJ, Yi Y, Smyth RJ, “A Dual-Tropic primary HIV-1 isolate that uses Fusin and the B-chemokine receptors CKR-5, CKR-3, CKR-2 as fusion cofactors”,Cell,vol. 85 pp. 1149-1158, 1996. |
[7] | Schols D, Struyf S, Van Damme J, et al. 1997. “Inhibition of T-tropic HIV strains by selective antagonization of the chemokine receptor cxcr4”. J. Exp. Med. 186(8):1383-1388. |
[8] | Nwankwo N, “Signal processing-based Bioinformatics methods for characterization and identification of Bio-functionalities of proteins”, PhD Thesis (submitted), De Montfort University, Leicester, United Kingdom, 2012. (Available at www.openthesis.org). |
[9] | Nwankwo N, Seker H, “HIV progression to AIDS: Bioinformatics approach to determining the mechanism of Action”,Curr. HIV Res.,vol. 11(1), pp. 30-42, 2013. |
[10] | Collman R, Balliet JW, Gregory SA, “An infectious molecular clone of an unusual macrophage-tropic and highly cytopathic strains of Human Immunodeficiency Virus type 1”, Journal of Virology, vol. 66(12), pp. 7517-7521 1992. |
[11] | Svicher V, D’Arrigo R, Alteri C, et al, “Performance of genotypic tropism testing in clinical practice using the Enhanced Sensitivity version of Trofile as reference assay: results from the Oscar study group”, New Microbiol., vol. 33(3) pp. 195-206, 2010. |
[12] | Blaak H, Vant-Wout AB, Brouwer M, et al, “In vivo hiv-1 infection of cd45ra+ cd4+ t cells is established primarily by syncytium-inducing variants and correlates with the rate of cd41 t cell decline”,PNAS,vol. 97(3), pp. 1269-1274, 1999. |
[13] | Nagy K, Clapham P, “Human T-cell leukemia virus type 1: Induction of Syncytia and inhibition by patients’ sera”, International Journal of Cancer, vol. 32(3) pp. 321-328, 1983. |
[14] | Nkengasong JN, Peeters M, Nys P, et al. 1995, “Infectious virus titer, replicative and syncytium-inducing capacity of human immunodeficiency virus type 1”, J Med Virol., vol. 45(1) pp. 78-81, 1995. |
[15] | Blaak H, Vant-Wout AB, Brouwer M, “In vivo hiv-1 infection of cd45ra+ cd4+ t cells is established primarily by syncytium-inducing variants and correlates with the rate of cd41 t cell decline”, PNAS, vol. 97(3) pp. 1269-1274, 1999. |
[16] | Veljkovic V, Niman HL, Glisic S, et al, “Identification of hemagglutinin structural domain and polymorphisms which may modulate swine h1n1 interactions with human receptor”, BMC Structural Biology, vol. 9(62) pp. 1-11, 2009. |
[17] | Veljkovic V. and Veljkovic N, “Characterization of conserved properties of hemagglutinin of h5n1 and human inuenza viruses: possible consequences for therapy and infection control”, BMC Structural Biology, vol. 9(21) pp. 1-11, 2009. |
[18] | W. O. F. A. H. (OIE), “Laboratory Methodologies for Bacterial Antimicrobial Susceptibility Test”, 2008. |
[19] | Zhao Q, et al, “A novel assay to identify entry inhibitors that block binding of HIV-1 gp120 to CCR5”, Virology, vol. 326(2) pp. 299-309, 2004. |
[20] | Princen K, et al, “Evaluation of SDF-1/CXCR4-induced Ca2+ signaling by fluorometeric imaging plate reader (FLIPR) and flow cytometry”,Cytometry A, vol. 51(1) pp. 35-45, 2003. |
[21] | JapourI,et al, “Standardized microtiter assay for determination of Syncytium Inducing Phenotype of Clinical Human Immunodeficiency Virus type 1 isolates”, J ClinMicrobiol., vol. 32(9), pp. 2291-2294, 1994. |
[22] | Secle´n E, Garrido C, Gonzalez MM, “High sensitivity of specific genotypic tools for detection of X4 variants in antiretroviral-experienced patients suitable to be treated with CCR5 antagonists”, AntimicrobChemother, vol. 65, pp. 1486–1492, 2010. |
[23] | W. O. F. A. H. (OIE), “International Standards on Antimicrobial Resistance”, 2008. |
[24] | Schweiker KL, Makhatadze GI, “A computational approach for the rational design of stable proteins and enzymes: optimization of surface charge-charge interactions”, Methods Enzymol, vol. 454, pp. 175-211, 2009. |
[25] | Jensen, MA, Li FS, van’tWout AB, et al, “Improved coreceptor usage prediction and genotypic monitoring of R5-to-X4 transition by motif analysis of HIV-1 env V3 loop sequences”, Journal of Virology, vol. 77, pp. 13376-13388, 2003. |
[26] | Jensen MA, Coetzer M, van 't Wout AB, et al, “A reliable phenotype predictor for human immunodeficiency virus type 1 subtype C based on Envelope V3 sequences”, Journal of Virology, vol. 80, pp. 4698-4704, 2006. |
[27] | Obermeier M, Ehret R, Berg T, et al, “Genotypic HIV-coreceptor tropism prediction with geno2pheno [CORECEPTOR]: differences depending on HIV-1 subtype“, Journal of the International AIDS Society, vol. 15(Suppl 4), pp. 1821-1824, 2012 |
[28] | Garrido C, Roulet V, Chueca N, et al, “Evaluation of eight different bioinformatics tools to predict viral tropism in different human immunodeficiency virus type 1 subtypes”, J ClinMicrobiol, vol. 46(3), pp. 887-91,2008. |
[29] | Cosic I, “Macromolecular Bioactivity: Is It Resonant Interaction between Macromolecules?-Theory and Application”, IEEE Transactions on Biomedical Engineering, vol. 41(I), pp. 1101-1114, 1994. |
[30] | Veljkovic V, Cosic I, Dimitrijevic B, et al, “Is it possible to analyze DNA and protein sequence by the method of digital signal processing”, IEEE Trans Biomed Eng., vol. 32(5), pp. 337-341, 1985. |
[31] | Veljkovic V, Glisic S, Veljkovic N, et al, Assessment of Hepatitis C Virus protein sequences with regard to interferon/ribavirin combination therapy response in patients with HCV genotype 1b, Vaccine, vol 32(48), pp. 6569-75, 2014. |
[32] | Jain E, Bairoch A, Duvaud S, et al, “Infrastructure for the life sciences: design and implementation of the uniprot website”, BMC Bioinformatics, vol. 10, pp. 136-154, 2009. |
[33] | Perovic VR, Muller CP, Niman HL, et al, “Novel Phylogenetic Algorithm to Monitor Human Tropism in Egyptian H5N1-HPAIV Reveals Evolution toward Efficient Human-to-Human Transmission”, PLoS ONE, vol. 8(4) pp. e61572, 2013. doi:10.1371/journal.pone.0061572 |
[34] | Smith SW, “The Scientist and Engineer's Guide to Digital Signal Processing”, California Technical Publishing, 2002. |
[35] | Vandekerckhove LPR, Wensing AMJ, Kaiser R, et al,“European guidelines on the clinical management of HIV-1 tropism testing”, Lancet Infect Dis., vol. 11, pp. 394–407, 2011. |
[36] | Jeffs SA, Shotton C, Balfe P, et al, “Truncated gp120 envelope glycoprotein of human immunodeficiency virus 1 elicits a broadly reactive neutralizing immune response”, J Gen Virol., vol. 83(Pt 11), pp. 2723-2732, 2002. |
[37] | Miller ED, Duus KM, Townsend M, et al, “Human immunodeficiency virus type 1 IIIB selected for replication in vivo exhibits increased envelope glycoproteins in virions without alteration in co-receptor usage: Separation of in vivo replication from macrophage tropism”, Journal of Virology, vol. 75(18), pp. 8498-8506, 2001. |
[38] | Collman R, Balliet JW, Gregory SA, et al, “An infectious molecular clone of an unusual macrophage-tropic and highly cytopathic strain of human immunodeficiency virus type 1”, Journal of Virology, vol. 66(12), pp. 7517-7521, 1992. |
[39] | Doliana R, Veljkovic V, “Emilins interact with anthrax protective antigen and inhibit toxin action in vitro",Matrix Biology, vol. 27, pp. 96-106, 2008. |
APA Style
Norbert Nwankwo, Michael Adikwu, Ignatus Okafor. (2015). HIV Tropism Prediction: Digital Signal Processing-Based Bioinformatics Approach is Non-Sequence Alignment Dependent. Computational Biology and Bioinformatics, 3(2), 21-30. https://doi.org/10.11648/j.cbb.20150302.11
ACS Style
Norbert Nwankwo; Michael Adikwu; Ignatus Okafor. HIV Tropism Prediction: Digital Signal Processing-Based Bioinformatics Approach is Non-Sequence Alignment Dependent. Comput. Biol. Bioinform. 2015, 3(2), 21-30. doi: 10.11648/j.cbb.20150302.11
AMA Style
Norbert Nwankwo, Michael Adikwu, Ignatus Okafor. HIV Tropism Prediction: Digital Signal Processing-Based Bioinformatics Approach is Non-Sequence Alignment Dependent. Comput Biol Bioinform. 2015;3(2):21-30. doi: 10.11648/j.cbb.20150302.11
@article{10.11648/j.cbb.20150302.11, author = {Norbert Nwankwo and Michael Adikwu and Ignatus Okafor}, title = {HIV Tropism Prediction: Digital Signal Processing-Based Bioinformatics Approach is Non-Sequence Alignment Dependent}, journal = {Computational Biology and Bioinformatics}, volume = {3}, number = {2}, pages = {21-30}, doi = {10.11648/j.cbb.20150302.11}, url = {https://doi.org/10.11648/j.cbb.20150302.11}, eprint = {https://article.sciencepublishinggroup.com/pdf/10.11648.j.cbb.20150302.11}, abstract = {Phenotypic and genotypic predictors forHIV/SIV tropism are available. The genotypic predictors are more rational. However, they are sequence alignment dependent only. Regrettably, non-homologous proteins are found to display common biological functionality. This indicates that sequence-dependent predictors cannot be trusted with appropriate classification of the HIV and SIV isolates, especially if the isolates belong to same tropic group but share divergent sequence alignment. There is therefore need for genotypic predictors that will incorporate embedded intrinsic biological characteristics of the HIV and SIV isolates in the determination of HIV tropism. Secondly, more than 30 positions with at least single mutation outside the V3 domain have been found to influence HIV Tropism. Disappointingly, the available sequence alignment-based HIV genotypic predictors engage only the hyper-variable region (V3) of the HIV gp120. This has resulted in inaccurate classification of HIV and SIV strains. Finally, available HIV genotypic predictors are found to lack the ability to identify and accurately evaluate the sequences of most HIV-1 non B clades, HIV-2 and SIV. Against this background, the ability of the Digital Signal Processing (DSP) Technique called Informational Spectrum Method (ISM), which does not engage sequence similarity but the embedded bio-functionalities of the entire gp120 sequence length to predict HIV and SIV tropism is therefore investigated. 83 isolates of HIV and SIV are subjected to ISM and three other procedures. Results are generated and findings correlated. For isolates, which are analyzable by the four procedures, the results from ISM and three other procedures are found to correlate. Using 50% affinity for the host CD4 as the cut-off, the tropism of the uncategorized isolates are predicted. ISM-based technique is adjudged a better procedure. It analyzes the sequences of all HIV (HIV-1 together with non B, and HIV-2) as well as SIV isolates including those that could not be investigated by other genotypic predictors. It engages the embedded biological characteristics rather than sequence similarity and utilizes the entire HIV gp120 sequence-length instead of V3 domain. This makes ISM-based procedure a better tool for over 180,000 isolates of HIV-1, HIV-2 and SIV in the UNIPROT database. Clinical approaches are unfeasible. This study recommends ISM technique principally for viral tropism prediction as it does not discriminate against HIV/SIVcategories. It suggests that further work be done to determine a suitable cut-off (as in geno2pheno[CORECEPTOR]), and the procedure in combination with other genotypic predictors be engaged in developing an algorithm for determining viral tropism.}, year = {2015} }
TY - JOUR T1 - HIV Tropism Prediction: Digital Signal Processing-Based Bioinformatics Approach is Non-Sequence Alignment Dependent AU - Norbert Nwankwo AU - Michael Adikwu AU - Ignatus Okafor Y1 - 2015/03/28 PY - 2015 N1 - https://doi.org/10.11648/j.cbb.20150302.11 DO - 10.11648/j.cbb.20150302.11 T2 - Computational Biology and Bioinformatics JF - Computational Biology and Bioinformatics JO - Computational Biology and Bioinformatics SP - 21 EP - 30 PB - Science Publishing Group SN - 2330-8281 UR - https://doi.org/10.11648/j.cbb.20150302.11 AB - Phenotypic and genotypic predictors forHIV/SIV tropism are available. The genotypic predictors are more rational. However, they are sequence alignment dependent only. Regrettably, non-homologous proteins are found to display common biological functionality. This indicates that sequence-dependent predictors cannot be trusted with appropriate classification of the HIV and SIV isolates, especially if the isolates belong to same tropic group but share divergent sequence alignment. There is therefore need for genotypic predictors that will incorporate embedded intrinsic biological characteristics of the HIV and SIV isolates in the determination of HIV tropism. Secondly, more than 30 positions with at least single mutation outside the V3 domain have been found to influence HIV Tropism. Disappointingly, the available sequence alignment-based HIV genotypic predictors engage only the hyper-variable region (V3) of the HIV gp120. This has resulted in inaccurate classification of HIV and SIV strains. Finally, available HIV genotypic predictors are found to lack the ability to identify and accurately evaluate the sequences of most HIV-1 non B clades, HIV-2 and SIV. Against this background, the ability of the Digital Signal Processing (DSP) Technique called Informational Spectrum Method (ISM), which does not engage sequence similarity but the embedded bio-functionalities of the entire gp120 sequence length to predict HIV and SIV tropism is therefore investigated. 83 isolates of HIV and SIV are subjected to ISM and three other procedures. Results are generated and findings correlated. For isolates, which are analyzable by the four procedures, the results from ISM and three other procedures are found to correlate. Using 50% affinity for the host CD4 as the cut-off, the tropism of the uncategorized isolates are predicted. ISM-based technique is adjudged a better procedure. It analyzes the sequences of all HIV (HIV-1 together with non B, and HIV-2) as well as SIV isolates including those that could not be investigated by other genotypic predictors. It engages the embedded biological characteristics rather than sequence similarity and utilizes the entire HIV gp120 sequence-length instead of V3 domain. This makes ISM-based procedure a better tool for over 180,000 isolates of HIV-1, HIV-2 and SIV in the UNIPROT database. Clinical approaches are unfeasible. This study recommends ISM technique principally for viral tropism prediction as it does not discriminate against HIV/SIVcategories. It suggests that further work be done to determine a suitable cut-off (as in geno2pheno[CORECEPTOR]), and the procedure in combination with other genotypic predictors be engaged in developing an algorithm for determining viral tropism. VL - 3 IS - 2 ER -