Proteomics

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Plasma proteome changes during the first week of human life in two independent cohorts


ABSTRACT: Introduction: Early life is characterized by heightened susceptibility to infections and is recognized as a major determinant of the immune system development and the overall health for the entire human lifespan. However, our knowledge of the development of the neonatal immune system is incomplete, limiting the development of novel preventative and therapeutic strategies, especially in newborns. To gain insight into the early immune system development and plasma proteome ontogeny, the Expanded Program on Immunization Consortium (EPIC) led by Professor Ofer Levy MD at Boston Children’s Hospital, Harvard Medical School and Tobias R. Kollmann Telethon Kids Institute, Australia as part of the Human Immunological Project Consortium (HIPC), established two independent cohorts of plasma from healthy newborns born by vaginal delivery during the first week of life. Methods: Blood samples were collected from 30 newborns in The Gambia (Medical Research Council Unit, The Gambia) at the day of birth (day of life, DOL 0) and at one of the follow-up visits on DOL1, DOL3, or DOL7. A similar validation cohort was collected in Papua New Guinea (PNG) (Institute for Medical Research, Papua New Guinea, Australasian) from 19 newborns. The plasma proteome was characterized by LC-MS on a Q Exactive using the proven and published plasma proteomics platform developed in the Steen Laboratory, led by Dr Hanno Steen, Director of Proteomics at Boston Children’s Hospital, Harvard Medical School, employing only microliter of plasma prepared in a 96-well plate format. The data was analyzed with MaxQuant. Results: We characterized 385 blood-plasma proteins. Utilizing the paired study design, we identified consistent changes related to ontogeny and cellular growth pathways in the blood-plasma proteome. Conclusion: This dataset allows for studying the early ontogeny of the plasma proteome, and in extension the early immune system development, in two independent healthy cohorts. Characterization of the plasma proteome may provide novel insight into new approaches to prevent, detect, and treat infectious diseases. Acknowledgements: We would like to thank all the participating families and all past and current members of the EPIC-HIPC, and the Steen Laboratory, without whom this study would not be possible. A special recognition goes to the teams who established the unique cohorts in The Gambia, by Professor Beate Kampmann and Dr Olubukola T. Idoko at The Gambia at the London School of Hygiene and Tropical Medicine, The Gambia, and in PNG, by Anita H.J. van der Biggelaar and William S. Pomat at Wesfarmers Centre of Vaccines and Infectious Diseases, Telethon Kids Institute, University of Western Australia Perth, Australia.

OTHER RELATED OMICS DATASETS IN: GSE123070GSE111404

INSTRUMENT(S): Q Exactive

ORGANISM(S): Homo Sapiens (human)

TISSUE(S): Blood Plasma

DISEASE(S): Disease Free

SUBMITTER: Tue Bjerg Bennike  

LAB HEAD: Hanno Steen

PROVIDER: PXD019817 | Pride | 2020-11-24

REPOSITORIES: Pride

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Dynamic molecular changes during the first week of human life follow a robust developmental trajectory.

Lee Amy H AH   Shannon Casey P CP   Amenyogbe Nelly N   Bennike Tue B TB   Diray-Arce Joann J   Idoko Olubukola T OT   Gill Erin E EE   Ben-Othman Rym R   Pomat William S WS   van Haren Simon D SD   Cao Kim-Anh Lê KL   Cox Momoudou M   Darboe Alansana A   Falsafi Reza R   Ferrari Davide D   Harbeson Daniel J DJ   He Daniel D   Bing Cai C   Hinshaw Samuel J SJ   Ndure Jorjoh J   Njie-Jobe Jainaba J   Pettengill Matthew A MA   Richmond Peter C PC   Ford Rebecca R   Saleu Gerard G   Masiria Geraldine G   Matlam John Paul JP   Kirarock Wendy W   Roberts Elishia E   Malek Mehrnoush M   Sanchez-Schmitz Guzmán G   Singh Amrit A   Angelidou Asimenia A   Smolen Kinga K KK   Brinkman Ryan R RR   Ozonoff Al A   Hancock Robert E W REW   van den Biggelaar Anita H J AHJ   Steen Hanno H   Tebbutt Scott J SJ   Kampmann Beate B   Levy Ofer O   Kollmann Tobias R TR  

Nature communications 20190312 1


Systems biology can unravel complex biology but has not been extensively applied to human newborns, a group highly vulnerable to a wide range of diseases. We optimized methods to extract transcriptomic, proteomic, metabolomic, cytokine/chemokine, and single cell immune phenotyping data from <1 ml of blood, a volume readily obtained from newborns. Indexing to baseline and applying innovative integrative computational methods reveals dramatic changes along a remarkably stable developmental traject  ...[more]

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