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BIOINFORMATICS

New bioinformatic approaches in conjunction with high resolution mass spectrometry data have been employed to type, subtype and determine the lineage of viral strains through single ion detection of signature peptides. This proteotyping approach (originating in 2009) has broad applicability and has been applied in this laboratory to classify influenza, parainfluenza and hepatitis viruses. The approach has recently been reviewed in Chem. Soc. Rev. in 2013 (see citation below).

 

Uddin R, Downard KM (2017) Subtyping of Hepatitis C Virus with High Resolution Mass Spectrometry, Clin. Mass Spectrom., 4-5: 19-24.   http://dx.doi.org/10.1016/j.clinms.2017.08.003

 

Fernandes ND, Downard KM (2014) Origins of the Reassortant H1N1 2009 Pandemic Influenza Virus by Proteotyping with Mass Spectrometry, J. Mass Spectrom., 49, 93-102.  http://dx.doi.org/10.1002/jms.3310

 

Fernandes ND, Downard KM (2014) Incorporation of a Proteotyping Approach using Mass Spectrometry for the Surveillance of the Influenza Virus in Cell Culture, J. Clin. Microbio., 52, 725-735.  http://dx.doi.org/10.1128/JCM.02315-13

 

Downard KM (2013) Proteotyping for the Rapid Identification of Pandemic Influenza Virus and other Biopathogens, Chem. Soc. Rev., 42: 8584-8595.  http://dx.doi.org/10.1039/C3CS60081E

 

Nguyen AP, Downard KM (2013) Subtyping of Influenza Neuraminidase using Mass Spectrometry, Analyst, 138, 1787- 1793.  http://dx.doi.org/10.1039/c3an00086a

 

Nguyen AP, Downard KM (2013) Proteotyping of the Parainfluenza Virus with High Resolution Mass Spectrometry, Anal. Chem., 85, 1097-1105.  http://dx.doi.org/10.1021/ac302962u

 

Ha J-W, Downard KM (2011) Evolution of H5N1 Influenza Virus through Proteotyping of Hemagglutinin with High Resolution Mass Spectrometry, Analyst, 136, 3259-3267.

 

Ha J-W, Schwahn AB, Downard KM (2011) Proteotyping to Establish Gene Origin within Reassortant Influenza Viruses, PLoS One, 6, e15771.

 

Schwahn AB, Downard KM (2011) Proteotyping to Establish the Lineage of Type A H1N1 and Type B Human Influenza Virus, J. Virol. Methods, 171: 117-122.

 

Schwahn AB, Wong JWH, Downard KM (2010) Rapid Differentiation of Seasonal and Pandemic H1N1 Influenza through Proteotyping of Viral Neuraminidase with Mass Spectrometry, Anal. Chem., 82, 4584-4590.

 

Schwahn AB, Wong JWH, Downard KM (2010) FluTyper - An Algorithm for Automated Typing and Subtyping of the Influenza Virus from High Resolution Mass Spectral Data, BMC Bioinformatics, 11: 266.

 

Schwahn AB, Wong JWH, Downard KM (2010) Typing of Human and Animal Strains of Influenza Virus with Conserved Signature Peptides of Matrix M1 Protein by High Resolution Mass Spectrometry, J. Virol. Methods, 165: 178-185.

 

Schwahn AB, Wong JWH, Downard KM (2010) Rapid typing and subtyping of vaccine strains of the influenza virus with high resolution mass spectrometry, Eur. J. Mass Spectrom., 16: 321-329.

 

Schwahn AB, Wong JWH, Downard KM (2009) Signature peptides of influenza nucleoprotein for the typing and subtyping of the virus by high resolution mass spectrometry, Analyst, 134: 2253- 2261.

 

Schwahn AB, Wong JWH, Downard KM (2009) Subtyping of the Influenza Virus by High Resolution Mass Spectrometry, Anal. Chem., 81, 3500–3506.

 

 

PHYLONUMERICS

 

An innovative and new approach has been developed to study the evolution of organisms at the molecular level from the perspective of expressed proteins without the need for either gene or protein sequences. The approach (originating in 2013) uses numerical mass map or fingerprint data routinely used in proteomics applications to identify proteins. The "mass trees" are found to be highly congruent with sequence based trees. Such a phylonumerics approach has been used to study mechanisms associated with epistasis and resistance, where mutations are identified and charted along branches of the trees.

 

Akand EH, Downard KM (2019) Mechanisms of Antiviral Resistance in Influenza Neuraminidase Revealed by a Mass Spectrometry Based Phylonumerics Approach, Mol. Phylogen. Evol., 135: 286-296.  https://doi.org/10.1016/j.ympev.2019.03.009

 

Akand EH, Downard KM (2018) Ancestral and Compensatory Mutations that Promote Antiviral Resistance in Influenza N1 Neuraminidase Revealed by a Phylonumerics Approach, J. Mol. Evol., 86(8): 546-553.   https://doi.org/10.1007/s00239-018-9866-4

 

Akand EH, Downard KM (2018) Identification of Epistatic Mutations and Insights into the Evolution of the Influenza Virus Using a Mass-Based Protein Phylogenetic Approach, Mol. Phylogenet. Evol., 121: 132-138.   http://dx.doi.org/10.1016/j.ympev.2018.01.009

 

Akand EH, Downard KM (2017) Mutational Analysis Employing a Phylogenetic Mass Tree Approach in a Study of the Evolution of the Influenza Virus, Mol. Phylogenet. Evol., 112: 209-217.  http://dx.doi.org/10.1016/j.ympev.2017.04.005

 

Ma S, Downard KM, Wong JWH (2017) Phylogenetic Analysis using Protein Mass Spectrometry, in Methods in Molecular Biology: Proteome Bioinformatics (eds. Mathivanan S, Keerthikumar S), Humana Press, NJ USA, pg. 135-146. (ISBN 978-1-4939-6738-4).   http://www.springer.com/gp/book/9781493967384

 

Ma S, Downard KM, Wong JWH (2015) FluClass: A Novel Algorithm and Approach to Score and Visualize the Phylogeny of the Influenza Virus using Mass Spectrometry, Anal. Chim. Acta,  895: 54-61.   http://dx.doi.org/10.1016/j.aca.2015.09.004

 

Swaminathan K, Downard KM (2014) Evolution of Influenza Neuraminidase and the Detection of Antiviral Resistant Strains Using Mass Trees, Anal. Chem., 86: 629–637.  http://dx.doi.org/10.1021/ac402892m

 

Lun ATL, Swaminathan K, Wong JWH, Downard KM (2013) Mass Trees – A New Phylogenetic Approach and Algorithm to Chart Evolutionary History with Mass Spectrometry, Anal. Chem., 85: 5475-5482.  http://dx.doi.org/10.1021/ac4005875

 

COMPUTATIONAL BIOLOGY

 

Molecular design, docking and companion experimental assays (both MS-based molecular and non-molecular) have been used to design and study the action of new drugs, particularly those which act as inhibitors of viral infection.

 

Uddin R, Downard KM (2018) Molecular Basis of Benzimidazole Inhibitors to Hepatitis C Virus Envelope Glycoprotein, Chem. Biol. Drug Design, 92: 1638-1646.

 

Lu R, Müller P, Downard KM (2015) Molecular Basis of Influenza Hemaglutinin Inhibition with an Entry-Blocker Peptide by Computational Docking and Mass Spectrometry, Antivir. Chem. Chemother., 24: 109-117.

 

Müller P, Downard KM (2015) Catechins Inhibit Influenza Neuraminidase and its Molecular Basis with Mass Spectrometry, J. Pharmaceut. Biomed. Anal. 111: 222-230.

 

Swaminathan K, Muller P, Downard KM (2014) Substituent Effects on the Binding of Natural Product Anthocyanidin Inhibitors to Influenza Neuraminidase with Mass Spectrometry, Anal. Chim. Acta, 828: 61-69.

 

Nasser Z, Swaminathan K, Muller P, Downard KM (2013) in-vitro Inhibition of the Influenza virus with the Anti-Viral Inhibitor Arbidol by a Proteomics based Approach with Mass Spectrometry, Antiviral Res., 100: 399-406.

 

Swaminathan K, Dyason JC, Maggioni A, von Itzstein M, Downard KM (2013) Binding of a Natural Anthocyanin Inhibitor to Influenza Neuraminidase by Mass Spectrometry, Anal. Bio. Chem., 405: 6563-6572.

 

 

 

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BIOINFORMATICS, PHYLONUMERICS & COMPUTATIONAL BIOLOGY