title: Cryptosporidium hominis gene catalog: a resource for the selection of novel Cryptosporidium vaccine candidates.
abstract: Human cryptosporidiosis, caused primarily by Cryptosporidium hominis and a subset of Cryptosporidium parvum, is a major cause of moderate-to-severe diarrhea in children under 5 years of age in developing countries and can lead to nutritional stunting and death. Cryptosporidiosis is particularly severe and potentially lethal in immunocompromised hosts. Biological and technical challenges have impeded traditional vaccinology approaches to identify novel targets for the development of vaccines against C. hominis, the predominant species associated with human disease. We deemed that the existence of genomic resources for multiple species in the genus, including a much-improved genome assembly and annotation for C. hominis, makes a reverse vaccinology approach feasible. To this end, we sought to generate a searchable online resource, termed C. hominis gene catalog, which registers all C. hominis genes and their properties relevant for the identification and prioritization of candidate vaccine antigens, including physical attributes, properties related to antigenic potential and expression data. Using bioinformatic approaches, we identified ∼400 C. hominis genes containing properties typical of surface-exposed antigens, such as predicted glycosylphosphatidylinositol (GPI)-anchor motifs, multiple transmembrane motifs and/or signal peptides targeting the encoded protein to the secretory pathway. This set can be narrowed further, e.g. by focusing on potential GPI-anchored proteins lacking homologs in the human genome, but with homologs in the other Cryptosporidium species for which genomic data are available, and with low amino acid polymorphism. Additional selection criteria related to recombinant expression and purification include minimizing predicted post-translation modifications and potential disulfide bonds. Forty proteins satisfying these criteria were selected from 3745 proteins in the updated C. hominis annotation. The immunogenic potential of a few of these is currently being tested.Database URL: http://cryptogc.igs.umaryland.edu.
authors.affiliation: Institute for Genome Sciences, University of Maryland School of Medicine, 801 West Baltimore Street, Baltimore, MD 21201, USA.|School of Systems Biology, George Mason University, 10900 University Boulevard, Manassas, VA 20110, USA.
authors.forename: Olukemi O
authors.initials: OO
authors.lastname: Ifeonu
authors.affiliation: Center for Vaccine Development, Institute for Global Health, and Department of Medicine, University of Maryland School of Medicine, 685 West Baltimore Street, Baltimore, MD 21201, USA.
authors.forename: Raphael
authors.initials: R
authors.lastname: Simon
authors.affiliation: Center for Vaccine Development, Institute for Global Health, and Department of Medicine, University of Maryland School of Medicine, 685 West Baltimore Street, Baltimore, MD 21201, USA.
authors.forename: Sharon M
authors.initials: SM
authors.lastname: Tennant
authors.affiliation: Department of Infectious Disease and Global Health, Tufts University Cummings School of Veterinary Medicine, 200 Westboro Road, North Grafton, MA 01536, USA.
authors.forename: Abhineet S
authors.initials: AS
authors.lastname: Sheoran
authors.affiliation: Institute for Genome Sciences, University of Maryland School of Medicine, 801 West Baltimore Street, Baltimore, MD 21201, USA.
authors.forename: Maria C
authors.initials: MC
authors.lastname: Daly
authors.affiliation: Institute for Genome Sciences, University of Maryland School of Medicine, 801 West Baltimore Street, Baltimore, MD 21201, USA.
authors.forename: Victor
authors.initials: V
authors.lastname: Felix
authors.affiliation: Department of Genetics, Institute of Bioinformatics and Center for Topical and Emerging Global Diseases, University of Georgia, 500 D.W. Brooks Drive, Athens, GA 30602, USA and.
authors.forename: Jessica C
authors.initials: JC
authors.lastname: Kissinger
authors.affiliation: Department of Infectious Disease and Global Health, Tufts University Cummings School of Veterinary Medicine, 200 Westboro Road, North Grafton, MA 01536, USA.
authors.forename: Giovanni
authors.initials: G
authors.lastname: Widmer
authors.affiliation: Center for Vaccine Development, Institute for Global Health, and Department of Medicine, University of Maryland School of Medicine, 685 West Baltimore Street, Baltimore, MD 21201, USA.
authors.forename: Myron M
authors.initials: MM
authors.lastname: Levine
authors.affiliation: Department of Infectious Disease and Global Health, Tufts University Cummings School of Veterinary Medicine, 200 Westboro Road, North Grafton, MA 01536, USA.
authors.forename: Saul
authors.initials: S
authors.lastname: Tzipori
authors.affiliation: Institute for Genome Sciences, University of Maryland School of Medicine, 801 West Baltimore Street, Baltimore, MD 21201, USA jcsilva@som.umaryland.edu.|School of Systems Biology, George Mason University, 10900 University Boulevard, Manassas, VA 20110, USA.|Department of Microbiology and Immunology, University of Maryland School of Medicine, 685 West Baltimore Street, Baltimore, MD 21201, USA.
authors.forename: Joana C
authors.initials: JC
authors.lastname: Silva
mesh_terms: D000818:Animals; D000953:Antigens, Protozoan / Q000235:genetics*; D003457:Cryptosporidiosis / Q000235:genetics* / Q000517:prevention & control; D003458:Cryptosporidium / Q000235:genetics*; D030541:Databases, Genetic; D018503:Genome, Protozoan; D006801:Humans; D016052:Protozoan Vaccines / Q000235:genetics*
chemical_list: D000953:Antigens, Protozoan; D016052:Protozoan Vaccines