title: Systems biology studies of adult paragonimus lung flukes facilitate the identification of immunodominant parasite antigens.
abstract: BACKGROUND
  Paragonimiasis is a food-borne trematode infection acquired by eating raw or undercooked crustaceans. It is a major public health problem in the far East, but it also occurs in South Asia, Africa, and in the Americas. Paragonimus worms cause chronic lung disease with cough, fever and hemoptysis that can be confused with tuberculosis or other non-parasitic diseases. Treatment is straightforward, but diagnosis is often delayed due to a lack of reliable parasitological or serodiagnostic tests. Hence, the purpose of this study was to use a systems biology approach to identify key parasite proteins that may be useful for development of improved diagnostic tests.
  
  
  RESULTS
  The transcriptome of adult Paragonimus kellicotti was sequenced with Illumina technology. Raw reads were pre-processed and assembled into 78,674 unique transcripts derived from 54,622 genetic loci, and 77,123 unique protein translations were predicted. A total of 2,555 predicted proteins (from 1,863 genetic loci) were verified by mass spectrometric analysis of total worm homogenate, including 63 proteins lacking homology to previously characterized sequences. Parasite proteins encoded by 321 transcripts (227 genetic loci) were reactive with antibodies from infected patients, as demonstrated by immunoaffinity purification and high-resolution liquid chromatography-mass spectrometry. Serodiagnostic candidates were prioritized based on several criteria, especially low conservation with proteins in other trematodes. Cysteine proteases, MFP6 proteins and myoglobins were abundant among the immunoreactive proteins, and these warrant further study as diagnostic candidates.
  
  
  CONCLUSIONS
  The transcriptome, proteome and immunolome of adult P. kellicotti represent a major advance in the study of Paragonimus species. These data provide a powerful foundation for translational research to develop improved diagnostic tests. Similar integrated approaches may be useful for identifying novel targets for drugs and vaccines in the future.
authors.affiliation: The Genome Institute at Washington University, St. Louis, Missouri, United States of America.
authors.forename: Samantha N
authors.initials: SN
authors.lastname: McNulty
authors.affiliation: Division of Infectious Diseases, Department of Medicine, Washington University School of Medicine, St. Louis, Missouri, United States of America.
authors.forename: Peter U
authors.initials: PU
authors.lastname: Fischer
authors.affiliation: Department of Cell Biology and Physiology, Washington University School of Medicine, St. Louis, Missouri, United States of America; Division of Endocrinology, Metabolism and Lipid Research, Department of Medicine, Washington University School of Medicine, St. Louis, Missouri, United States of America.
authors.forename: R Reid
authors.initials: RR
authors.lastname: Townsend
authors.affiliation: Division of Infectious Diseases, Department of Medicine, Washington University School of Medicine, St. Louis, Missouri, United States of America.
authors.forename: Kurt C
authors.initials: KC
authors.lastname: Curtis
authors.affiliation: Division of Infectious Diseases, Department of Medicine, Washington University School of Medicine, St. Louis, Missouri, United States of America.
authors.forename: Gary J
authors.initials: GJ
authors.lastname: Weil
authors.affiliation: The Genome Institute at Washington University, St. Louis, Missouri, United States of America; Division of Infectious Diseases, Department of Medicine, Washington University School of Medicine, St. Louis, Missouri, United States of America.
authors.forename: Makedonka
authors.initials: M
authors.lastname: Mitreva
mesh_terms: D000328:Adult; D000349:Africa; D000818:Animals; D000947:Antigens, Helminth / Q000276:immunology*; D001208:Asia; D001483:Base Sequence; D005260:Female; D005334:Fever / Q000175:diagnosis / Q000469:parasitology; D005517:Foodborne Diseases / Q000469:parasitology*; D006801:Humans; D016056:Immunodominant Epitopes / Q000276:immunology*; D008297:Male; D010237:Paragonimiasis / Q000175:diagnosis* / Q000469:parasitology; D010238:Paragonimus / Q000254:growth & development / Q000276:immunology* / Q000302:isolation & purification; D020543:Proteome / Q000032:analysis; D017422:Sequence Analysis, DNA; D049490:Systems Biology; D059467:Transcriptome / Q000235:genetics; D014376:Tuberculosis / Q000175:diagnosis
chemical_list: D000947:Antigens, Helminth; D016056:Immunodominant Epitopes; D020543:Proteome