title: Vaccine design via nonnegative lasso-based variable selection.
abstract: There are many different strains of malaria parasites, each represented by a unique sequence of amino acids. A desirable vaccine would match the amino acid sequence of the parasite antigen. Because of the three-dimensional structure of protein, not all sites in the amino acid sequence participate in the binding between the vaccine-induced antibody and the parasite antigen. Nor do all sites have equal importance. In this work, we apply a nonnegative lasso-based variable selection to identify the 'important' amino acid sites and evaluate their relative importance. We then define a metric, the functional coverage, to measure the 'effective' matching in the amino acid sequence between the vaccine and the parasite. With the variable selection procedure, development of a vaccine needs only to target the important sites, and the potential effectiveness of a vaccine candidate is reflected by the functional coverage. Published 2015. This article is a U.S. Government work and is in the public domain in the USA.
authors: Biostatistics Research Branch, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD, U.S.A.
authors: Zonghui
authors: Z
authors: Hu
authors: Dean A
authors: DA
authors: Follmann
authors: Kazutoyo
authors: K
authors: Miura
mesh_terms: D000595:Amino Acid Sequence / Q000187:drug effects*; D003198:Computer Simulation; D015195:Drug Design; D006801:Humans; D016014:Linear Models; D008288:Malaria / Q000276:immunology* / Q000469:parasitology / Q000517:prevention & control; D017780:Malaria Vaccines / Q000276:immunology*
chemical_list: D017780:Malaria Vaccines
keywords: amino acid sequence; malaria vaccine; nonnegative lasso regression; seemingly independent screening
references: Proc Natl Acad Sci U S A. 2008 Jun 3;105(22):7857-62
references: 18515425
references: Proc Natl Acad Sci U S A. 2014 Jul 15;111(28):10311-6
references: 24958881
references: Malar J. 2011;10:182
references: 21726452
references: Infect Immun. 2013 May;81(5):1491-501
references: 23429537
references: N Engl J Med. 2011 Sep 15;365(11):1004-13
references: 21916638
references: Proc Natl Acad Sci U S A. 2007 Jul 24;104(30):12488-93
references: 17636123
references: J R Stat Soc Series B Stat Methodol. 2008;70(5):849-911
references: 19603084
references: PLoS One. 2012;7(12):e51023
references: 23227229
references: Infect Immun. 2005 Jun;73(6):3677-85
references: 15908397