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Probabilistic data integration identifies reliable gametocyte-specific proteins and transcripts in malaria parasites.
Meerstein-Kessel, Lisette; van der Lee, Robin; Stone, Will; Lanke, Kjerstin; Baker, David A; Alano, Pietro; Silvestrini, Francesco; Janse, Chris J; Khan, Shahid M; van de Vegte-Bolmer, Marga; Graumans, Wouter; Siebelink-Stoter, Rianne; Kooij, Taco W A; Marti, Matthias; Drakeley, Chris; Campo, Joseph J; van Dam, Teunis J P; Sauerwein, Robert; Bousema, Teun; Huynen, Martijn A.
Afiliação
  • Meerstein-Kessel L; Centre for Molecular and Biomolecular Informatics, Radboud Institute for Molecular Life Sciences, Radboud university medical center, Nijmegen, The Netherlands.
  • van der Lee R; Department of Medical Microbiology, Radboud university medical center, Nijmegen, The Netherlands.
  • Stone W; Centre for Molecular and Biomolecular Informatics, Radboud Institute for Molecular Life Sciences, Radboud university medical center, Nijmegen, The Netherlands.
  • Lanke K; Centre for Molecular Medicine and Therapeutics, Department of Medical Genetics, BC Children's Hospital Research Institute, University of British Columbia, Vancouver, BC, Canada.
  • Baker DA; Department of Medical Microbiology, Radboud university medical center, Nijmegen, The Netherlands.
  • Alano P; Department of Immunology and Infection, Faculty of Infectious and Tropical Diseases, London School of Hygiene & Tropical Medicine, London, United Kingdom.
  • Silvestrini F; Department of Medical Microbiology, Radboud university medical center, Nijmegen, The Netherlands.
  • Janse CJ; Department of Pathogen Molecular Biology, Faculty of Infectious and Tropical Diseases, London School of Hygiene & Tropical Medicine, London, United Kingdom.
  • Khan SM; Dipartimento Malattie Infettive, Istituto Superiore di Sanità, Rome, Italy.
  • van de Vegte-Bolmer M; Dipartimento Malattie Infettive, Istituto Superiore di Sanità, Rome, Italy.
  • Graumans W; Department of Parasitology, Leiden University Medical Center, Leiden, The Netherlands.
  • Siebelink-Stoter R; Department of Parasitology, Leiden University Medical Center, Leiden, The Netherlands.
  • Kooij TWA; Department of Medical Microbiology, Radboud university medical center, Nijmegen, The Netherlands.
  • Marti M; Department of Medical Microbiology, Radboud university medical center, Nijmegen, The Netherlands.
  • Drakeley C; Department of Medical Microbiology, Radboud university medical center, Nijmegen, The Netherlands.
  • Campo JJ; Department of Medical Microbiology, Radboud university medical center, Nijmegen, The Netherlands.
  • van Dam TJP; Wellcome Trust Center for Molecular Parasitology, Institute of Infection, Immunity and Inflammation, College of Medical Veterinary & Life Sciences, University of Glasgow, Glasgow, Scotland, United Kingdom.
  • Sauerwein R; Department of Immunology and Infection, Faculty of Infectious and Tropical Diseases, London School of Hygiene & Tropical Medicine, London, United Kingdom.
  • Bousema T; Antigen Discovery Inc., Irvine, California, USA.
  • Huynen MA; Centre for Molecular and Biomolecular Informatics, Radboud Institute for Molecular Life Sciences, Radboud university medical center, Nijmegen, The Netherlands.
Sci Rep ; 8(1): 410, 2018 01 11.
Article em En | MEDLINE | ID: mdl-29323249
ABSTRACT
Plasmodium gametocytes are the sexual forms of the malaria parasite essential for transmission to mosquitoes. To better understand how gametocytes differ from asexual blood-stage parasites, we performed a systematic analysis of available 'omics data for P. falciparum and other Plasmodium species. 18 transcriptomic and proteomic data sets were evaluated for the presence of curated "gold standards" of 41 gametocyte-specific versus 46 non-gametocyte genes and integrated using Bayesian probabilities, resulting in gametocyte-specificity scores for all P. falciparum genes. To illustrate the utility of the gametocyte score, we explored newly predicted gametocyte-specific genes as potential biomarkers of gametocyte carriage and exposure. We analyzed the humoral immune response in field samples against 30 novel gametocyte-specific antigens and found five antigens to be differentially recognized by gametocyte carriers as compared to malaria-infected individuals without detectable gametocytes. We also validated the gametocyte-specificity of 15 identified gametocyte transcripts on culture material and samples from naturally infected individuals, resulting in eight transcripts that were >1000-fold higher expressed in gametocytes compared to asexual parasites and whose transcript abundance allowed gametocyte detection in naturally infected individuals. Our integrated genome-wide gametocyte-specificity scores provide a comprehensive resource to identify targets and monitor P. falciparum gametocytemia.
Assuntos

Texto completo: 1 Base de dados: MEDLINE Assunto principal: Plasmodium / Perfilação da Expressão Gênica / Proteômica / Malária Tipo de estudo: Prognostic_studies Limite: Animals / Humans Idioma: En Ano de publicação: 2018 Tipo de documento: Article

Texto completo: 1 Base de dados: MEDLINE Assunto principal: Plasmodium / Perfilação da Expressão Gênica / Proteômica / Malária Tipo de estudo: Prognostic_studies Limite: Animals / Humans Idioma: En Ano de publicação: 2018 Tipo de documento: Article