Journal article
Dynamic molecular changes during the first week of human life follow a robust developmental trajectory.
Amy H Lee, Casey P Shannon, Nelly Amenyogbe, Tue B Bennike, Joann Diray-Arce, Olubukola T Idoko, Erin E Gill, Rym Ben-Othman, William S Pomat, Simon D van Haren, Kim-Anh Lê Cao, Momoudou Cox, Alansana Darboe, Reza Falsafi, Davide Ferrari, Daniel J Harbeson, Daniel He, Cai Bing, Samuel J Hinshaw, Jorjoh Ndure Show all
Nature Communications | Nature Research (part of Springer Nature) | Published : 2019
Abstract
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 trajectory over the first week of life. This is most evident in changes of interferon and complement pathways, as well as neutrophil-associated signaling. Validated across two independent cohorts of newborns..
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Funding Acknowledgements
We would like to thank all the participants and their parents for their time and willingness to support this study. Research reported in this publication was supported by the National Institute of Allergy and Infectious Diseases of the National Institutes of Health as part of the Human Immunology Project consortium under 5U19AI118608-02. The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health. T.R.K.'s laboratory is supported by a Michael Smith Foundation for Health Research Career Investigator Award. O.L.'s laboratory is supported by the following U.S. National Institutes of Health (NIH)/National Institutes of Allergy and Infectious Diseases (NIAID) awards: Molecular Mechanisms of Combination Adjuvants (1U01AI124284-01), Adjuvant Discovery Program Contract No. HHSN272201400052C and Human Immunology Project Consortium (U19AI118608) as well as an internal Boston Children's Hospital award to the Precision Vaccines Program. B.K. is supported by grants from the MRC/UKRI (MC_UP_A900/1122, MC_UP_A900/115, MR/R005990/1), and the additional field team and laboratory staff at the MRC Unit in The Gambia. Recruitment of the cohort of newborns in Papua New Guinea was funded by seed funding awarded to A.H.J.v.d.B from the Wesfarmers Centre of Vaccines and Infectious Diseases, Telethon Kids Institute. The work in R.E.W. H.'s lab was initially supported by the Canadian Institutes for Health Research grant #FDN-154287 and he holds a Canada Research Chair in Health and Genomics and a UBC Killam Professorship. R.R.B.'s laboratory is supported by an award from Natural Sciences and Engineering Research Council of Canada. The Lundbeck Foundation (R181-2014-3372), The Carlsberg Foundation (CF14-0561), and A.P. Moller Foundation are acknowledged for grants enabling T.B.B.'s work. K.-A.L.C. is supported in part by the National Health and Medical Research Council (NHMRC) Career Development fellowship (GNT1087415). We gratefully acknowledge the support from Drs. Gary Fleisher, Michael Wessels and Ken Kraft as well as Maria Crenshaw, Mark Liu, Kerry McEnaney and Diana Vo (all BCH); Susan Farmer, Manish Sadarangani, Aaron Liu, Gordean Bjornson (all UBC). The Expanded Program on Immunization Consortium (EPIC) contributed collectively to this study. EPIC is an association of academic centers partnering to conduct systems biology studies in newborns and infants, comprised of the investigators listed above at Boston Children's Hospital (BCH), University of British Columbia (UBC), Medical Research Council Unit The Gambia (MRCG), Universite libre de Bruxelles, Telethon Kids Institute and University of Western Australia, and the Papua New Guinea Institute for Medical Research (PNG-IMR).