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Nat Commun. 2019 Mar 12;10(1):1092. doi: 10.1038/s41467-019-08794-x.

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

Author information

1
Department of Microbiology & Immunology, University of British Columbia, 1365-2350 Health Sciences Mall, Vancouver,  BC, V6T 1Z3, Canada.
2
PROOF Centre of Excellence, 10th Floor, 1190 Hornby Street, Vancouver, BC, V6Z 2K5, Canada.
3
Department of Experimental Medicine, University of British Columbia, 2775 Laurel Street, 10th Floor, Room 10117, Vancouver, BC, V5Z 1M9, Canada.
4
Telethon Kids Institute, 100 Roberts Road, Subiaco, 6008, Australia.
5
Department of Pathology, Boston Children's Hospital, BCH 3108, 300 Longwood Ave, Boston, MA, 02115, USA.
6
Precision Vaccines Program, Division of Infectious Diseases, Boston Children's Hospital, 300 Longwood Ave, BCH 3104, Boston, MA, 02115, USA.
7
Harvard Medical School, 25 Shattuck Street, Boston, MA, 02115, USA.
8
Vaccines & Immunity Theme, Medical Research Council Unit The Gambia at the London School of Hygiene and Tropical Medicine, Atlantic Boulevard, P.O. Box 273, Banjul, Gambia.
9
Center for International Health, Medical Center of the University of Munich (LMU), Munich, Germany.
10
Department of Pediatrics, BC Children's Hospital, University of British Columbia, Rm 2D19, 4480 Oak Street, Vancouver, BC, V6H 3V4, Canada.
11
Papua New Guinea Institute of Medical Research, Homate Street, Goroka, Eastern Highlands Province, Papua New Guinea.
12
Statistical Genomics, School of Mathematics and Statistics, Melbourne Integrative Genomics, Centre for Systems Genomics, The University of Melbourne, Building 184 Ground Floor, Parkville, VIC, 3010, Australia.
13
Graduate Program in Bioinformatics, BCCA, 100-570 West 7th Avenue, Vancouver, BC, V5Z 4S6, Canada.
14
Division of Paediatrics, School of Medicine, University of Western Australia, 35 Stirling Highway, Nedlands, WA, 6009, Australia.
15
Wesfarmers Centre of Vaccines and Infectious Diseases, Telethon Kids Institute, University of Western Australia Perth, 15 Hospital Avenue, Nedlands, WA, 6009, Australia.
16
BC Cancer Agency, 686 West Broadway, Suite 500, Vancouver, BC, V5Z 1G1, Canada.
17
Department of Pathology and Laboratory Medicine, Faculty of Medicine, University of British Columbia, Rm. G227-2211 Wesbrook Mall, Vancouver, BC, V6T 2B5, Canada.
18
Division of Newborn Medicine, Boston Children's Hospital, 300 Longwood Ave, BCH 3146, Boston, MA, 02115, USA.
19
Department of Medical Genetics, University of British Columbia, Vancouver, V6T1Z4, BC, Canada.
20
Center for Applied Pediatric Quality Analytics, Boston Children's Hospital, Boston, 02115, MA, USA.
21
UBC Centre for Heart and Lung Innovation, Vancouver, V6T1Z4, BC, Canada.
22
Department of Medicine, Division of Respiratory Medicine, UBC, Vancouver, V6T1Z4, BC, Canada.
23
The Vaccine Centre, Faculty of Infectious and Tropical Diseases, London School of Hygiene and Tropical Medicine, London, WC1E 7HT, UK.
24
Precision Vaccines Program, Division of Infectious Diseases, Boston Children's Hospital, 300 Longwood Ave, BCH 3104, Boston, MA, 02115, USA. ofer.levy@childrens.harvard.edu.
25
Harvard Medical School, 25 Shattuck Street, Boston, MA, 02115, USA. ofer.levy@childrens.harvard.edu.
26
Broad Institute of MIT & Harvard, Cambridge, 02142, MA, USA. ofer.levy@childrens.harvard.edu.
27
Department of Experimental Medicine, University of British Columbia, 2775 Laurel Street, 10th Floor, Room 10117, Vancouver, BC, V5Z 1M9, Canada. tkollm@mac.com.
28
Department of Pediatrics, BC Children's Hospital, University of British Columbia, Rm 2D19, 4480 Oak Street, Vancouver, BC, V6H 3V4, Canada. tkollm@mac.com.
29
Telethon Kids Institute, 100 Roberts Road, Subiaco, 6008, Australia. tkollm@mac.com.

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 from West Africa and Australasia, a robust and common trajectory emerges, suggesting a purposeful rather than random developmental path. Systems biology and innovative data integration can provide fresh insights into the molecular ontogeny of the first week of life, a dynamic developmental phase that is key for health and disease.

PMID:
30862783
PMCID:
PMC6414553
DOI:
10.1038/s41467-019-08794-x
[Indexed for MEDLINE]
Free PMC Article

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