Probabilistic data integration identifies reliable gametocyte-specific proteins and transcripts in malaria parasites
Probabilistic data integration identifies reliable gametocyte-specific proteins and transcripts in malaria parasites
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.
Lanke Kjerstin、Alano Pietro、Janse Chris J、Khan Shahid M、Siebelink-Stoter Rianne、Drakeley Chris、Sauerwein Robert、van de Vegte-Bolmer Marga、Graumans Wouter、Baker David A、van der Lee Robin、van Dam Teunis JP、Silvestrini Francesco、Meerstein-Kessel Lisette、Marti Matthias、Huynen Martijn A、Kooij Taco WA、Campo Joseph J.、Bousema Teun、Stone Will
Department of Medical Microbiology, Radboud university medical centerDipartimento Malattie Infettive, Istituto Superiore di Sanit¨¤Department of Parasitology, Leiden University Medical CenterDepartment of Parasitology, Leiden University Medical CenterDepartment of Medical Microbiology, Radboud university medical centerDepartment of Immunology and Infection, Faculty of Infectious and Tropical Diseases, London School of Hygiene & Tropical MedicineDepartment of Medical Microbiology, Radboud university medical centerDepartment of Medical Microbiology, Radboud university medical centerDepartment of Medical Microbiology, Radboud university medical centerDepartment of Pathogen Molecular Biology, Faculty of Infectious and Tropical Diseases, London School of Hygiene & Tropical MedicineCentre for Molecular and Biomolecular Informatics, Radboud Institute for Molecular Life Sciences, Radboud university medical center, Nijmegen||Centre for Molecular Medicine and Therapeutics, Department of Medical Genetics, BC Children?ˉs Hospital Research Institute, University of British ColumbiaCentre for Molecular and Biomolecular Informatics, Radboud Institute for Molecular Life Sciences, Radboud university medical center, Nijmegen||Theoretical Biology and Bioinformatics, Department of Biology, Utrecht UniversityDipartimento Malattie Infettive, Istituto Superiore di Sanit¨¤Centre for Molecular and Biomolecular Informatics, Radboud Institute for Molecular Life Sciences, Radboud university medical center, Nijmegen||Department of Medical Microbiology, Radboud university medical centerWellcome Trust Center for Molecular Parasitology, Institute of Infection, Immunity and Inflammation, College of Medical Veterinary & Life Sciences, University of GlasgowCentre for Molecular and Biomolecular Informatics, Radboud Institute for Molecular Life Sciences, Radboud university medical center, NijmegenDepartment of Medical Microbiology, Radboud university medical centerAntigen Discovery Inc.Department of Medical Microbiology, Radboud university medical centerDepartment of Medical Microbiology, Radboud university medical center||Department of Immunology and Infection, Faculty of Infectious and Tropical Diseases, London School of Hygiene & Tropical Medicine
基础医学生物科学研究方法、生物科学研究技术分子生物学
Lanke Kjerstin,Alano Pietro,Janse Chris J,Khan Shahid M,Siebelink-Stoter Rianne,Drakeley Chris,Sauerwein Robert,van de Vegte-Bolmer Marga,Graumans Wouter,Baker David A,van der Lee Robin,van Dam Teunis JP,Silvestrini Francesco,Meerstein-Kessel Lisette,Marti Matthias,Huynen Martijn A,Kooij Taco WA,Campo Joseph J.,Bousema Teun,Stone Will.Probabilistic data integration identifies reliable gametocyte-specific proteins and transcripts in malaria parasites[EB/OL].(2025-03-28)[2025-08-14].https://www.biorxiv.org/content/10.1101/199356.点此复制
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