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.

The first week of life impacts health for all of life, but the mechanisms are little-understood. Here the authors extract multi-omic data from small volumes of blood to study the dynamic molecular changes during the first week of life, revealing a robust developmental trajectory common to different populations.

Details

Title
Dynamic molecular changes during the first week of human life follow a robust developmental trajectory
Author
Lee, Amy H 1   VIAFID ORCID Logo  ; Shannon, Casey P 2   VIAFID ORCID Logo  ; Amenyogbe Nelly 3 ; Bennike, Tue B 4   VIAFID ORCID Logo  ; Diray-Arce Joann 5 ; Idoko Olubukola T 6 ; Gill, Erin E 1 ; Ben-Othman, Rym 7 ; Pomat, William S 8 ; van Haren Simon D 5 ; Cao Kim-Anh Lê 9   VIAFID ORCID Logo  ; Cox Momoudou 10 ; Darboe Alansana 10   VIAFID ORCID Logo  ; Falsafi Reza 1 ; Ferrari Davide 9 ; Harbeson, Daniel J 11 ; He, Daniel 2   VIAFID ORCID Logo  ; Cai, Bing 7 ; Hinshaw, Samuel J 12 ; Jorjoh, Ndure 13 ; Njie-Jobe Jainaba 13 ; Pettengill, Matthew A 14 ; Richmond, Peter C 15 ; Ford, Rebecca 8 ; Saleu Gerard 8 ; Masiria Geraldine 8 ; Matlam, John Paul 8 ; Kirarock Wendy 8 ; Roberts Elishia 16 ; Malek Mehrnoush 17 ; Sanchez-Schmitz, Guzmán 5 ; Singh, Amrit 18   VIAFID ORCID Logo  ; Angelidou Asimenia 19 ; Smolen, Kinga K 5 ; Vo, Diana 14 ; Kraft, Ken 5 ; McEnaney Kerry 20 ; Vignolo Sofia 14 ; Marchant Arnaud 21 ; Brinkman, Ryan R 22 ; Ozonoff Al 23 ; Hancock Robert E W 1   VIAFID ORCID Logo  ; van den Biggelaar Anita H J 24 ; Steen Hanno 25   VIAFID ORCID Logo  ; Tebbutt, Scott J 26   VIAFID ORCID Logo  ; Kampmann Beate 27 ; Levy, Ofer 28   VIAFID ORCID Logo  ; Kollmann, Tobias R 29   VIAFID ORCID Logo 

 University of British Columbia, Department of Microbiology & Immunology, Vancouver, Canada (GRID:grid.17091.3e) (ISNI:0000 0001 2288 9830) 
 PROOF Centre of Excellence, Vancouver, Canada (GRID:grid.460559.b) 
 University of British Columbia, Department of Experimental Medicine, Vancouver, Canada (GRID:grid.17091.3e) (ISNI:0000 0001 2288 9830); Telethon Kids Institute, Subiaco, Australia (GRID:grid.414659.b) (ISNI:0000 0000 8828 1230) 
 Boston Children’s Hospital, Department of Pathology, Boston, USA (GRID:grid.2515.3) (ISNI:0000 0004 0378 8438); Boston Children’s Hospital, Precision Vaccines Program, Division of Infectious Diseases, Boston, USA (GRID:grid.2515.3) (ISNI:0000 0004 0378 8438); Harvard Medical School, Boston, USA (GRID:grid.38142.3c) (ISNI:000000041936754X) 
 Boston Children’s Hospital, Precision Vaccines Program, Division of Infectious Diseases, Boston, USA (GRID:grid.2515.3) (ISNI:0000 0004 0378 8438); Harvard Medical School, Boston, USA (GRID:grid.38142.3c) (ISNI:000000041936754X) 
 Vaccines & Immunity Theme, Medical Research Council Unit The Gambia at the London School of Hygiene and Tropical Medicine, Banjul, Gambia (GRID:grid.38142.3c); Medical Center of the University of Munich (LMU), Center for International Health, Munich, Germany (GRID:grid.5252.0) (ISNI:0000 0004 1936 973X) 
 University of British Columbia, Department of Pediatrics, BC Children’s Hospital, Vancouver, Canada (GRID:grid.17091.3e) (ISNI:0000 0001 2288 9830) 
 Papua New Guinea Institute of Medical Research, Goroka, Papua New Guinea (GRID:grid.417153.5) (ISNI:0000 0001 2288 2831) 
 The University of Melbourne, Statistical Genomics, School of Mathematics and Statistics, Melbourne Integrative Genomics, Centre for Systems Genomics, Parkville, Australia (GRID:grid.1008.9) (ISNI:0000 0001 2179 088X) 
10  Vaccines & Immunity Theme, Medical Research Council Unit The Gambia at the London School of Hygiene and Tropical Medicine, Banjul, Gambia (GRID:grid.1008.9) 
11  University of British Columbia, Department of Experimental Medicine, Vancouver, Canada (GRID:grid.17091.3e) (ISNI:0000 0001 2288 9830) 
12  University of British Columbia, Department of Microbiology & Immunology, Vancouver, Canada (GRID:grid.17091.3e) (ISNI:0000 0001 2288 9830); BCCA, Graduate Program in Bioinformatics, Vancouver, Canada (GRID:grid.248762.d) (ISNI:0000 0001 0702 3000) 
13  Vaccines & Immunity Theme, Medical Research Council Unit The Gambia at the London School of Hygiene and Tropical Medicine, Banjul, Gambia (GRID:grid.248762.d) 
14  Boston Children’s Hospital, Precision Vaccines Program, Division of Infectious Diseases, Boston, USA (GRID:grid.2515.3) (ISNI:0000 0004 0378 8438) 
15  Division of Paediatrics, School of Medicine, University of Western Australia, Nedlands, Australia (GRID:grid.1012.2) (ISNI:0000 0004 1936 7910); University of Western Australia Perth, Wesfarmers Centre of Vaccines and Infectious Diseases, Telethon Kids Institute, Nedlands, Australia (GRID:grid.1012.2) (ISNI:0000 0004 1936 7910) 
16  Vaccines & Immunity Theme, Medical Research Council Unit The Gambia at the London School of Hygiene and Tropical Medicine, Banjul, Gambia (GRID:grid.417153.5) 
17  BC Cancer Agency, Vancouver, Canada (GRID:grid.248762.d) (ISNI:0000 0001 0702 3000) 
18  PROOF Centre of Excellence, Vancouver, Canada (GRID:grid.460559.b); University of British Columbia, Department of Pathology and Laboratory Medicine, Faculty of Medicine, Vancouver, Canada (GRID:grid.17091.3e) (ISNI:0000 0001 2288 9830) 
19  Boston Children’s Hospital, Precision Vaccines Program, Division of Infectious Diseases, Boston, USA (GRID:grid.2515.3) (ISNI:0000 0004 0378 8438); Harvard Medical School, Boston, USA (GRID:grid.38142.3c) (ISNI:000000041936754X); Boston Children’s Hospital, Division of Newborn Medicine, Boston, USA (GRID:grid.2515.3) (ISNI:0000 0004 0378 8438) 
20  Boston Children’s Hospital, Precision Vaccines Program, Division of Infectious Diseases, Boston, USA (GRID:grid.2515.3) (ISNI:0000 0004 0378 8438); University of British Columbia, Department of Medical Genetics, Vancouver, Canada (GRID:grid.17091.3e) (ISNI:0000 0001 2288 9830) 
21  Institute for Medical Immunology, Université libre de Bruxelles, Gosselies, Belgium (GRID:grid.4989.c) (ISNI:0000 0001 2348 0746) 
22  BC Cancer Agency, Vancouver, Canada (GRID:grid.248762.d) (ISNI:0000 0001 0702 3000); University of British Columbia, Department of Medical Genetics, Vancouver, Canada (GRID:grid.17091.3e) (ISNI:0000 0001 2288 9830) 
23  Boston Children’s Hospital, Precision Vaccines Program, Division of Infectious Diseases, Boston, USA (GRID:grid.2515.3) (ISNI:0000 0004 0378 8438); Harvard Medical School, Boston, USA (GRID:grid.38142.3c) (ISNI:000000041936754X); Boston Children’s Hospital, Center for Applied Pediatric Quality Analytics, Boston, USA (GRID:grid.2515.3) (ISNI:0000 0004 0378 8438) 
24  University of Western Australia Perth, Wesfarmers Centre of Vaccines and Infectious Diseases, Telethon Kids Institute, Nedlands, Australia (GRID:grid.1012.2) (ISNI:0000 0004 1936 7910) 
25  Boston Children’s Hospital, Department of Pathology, Boston, USA (GRID:grid.2515.3) (ISNI:0000 0004 0378 8438); Boston Children’s Hospital, Precision Vaccines Program, Division of Infectious Diseases, Boston, USA (GRID:grid.2515.3) (ISNI:0000 0004 0378 8438); Vaccines & Immunity Theme, Medical Research Council Unit The Gambia at the London School of Hygiene and Tropical Medicine, Banjul, Gambia (GRID:grid.2515.3) 
26  PROOF Centre of Excellence, Vancouver, Canada (GRID:grid.460559.b); UBC Centre for Heart and Lung Innovation, Vancouver, Canada (GRID:grid.17091.3e) (ISNI:0000 0001 2288 9830); UBC, Department of Medicine, Division of Respiratory Medicine, Vancouver, Canada (GRID:grid.17091.3e) (ISNI:0000 0001 2288 9830) 
27  Vaccines & Immunity Theme, Medical Research Council Unit The Gambia at the London School of Hygiene and Tropical Medicine, Banjul, Gambia (GRID:grid.17091.3e); London School of Hygiene and Tropical Medicine, The Vaccine Centre, Faculty of Infectious and Tropical Diseases, London, UK (GRID:grid.8991.9) (ISNI:0000 0004 0425 469X) 
28  Boston Children’s Hospital, Precision Vaccines Program, Division of Infectious Diseases, Boston, USA (GRID:grid.2515.3) (ISNI:0000 0004 0378 8438); Harvard Medical School, Boston, USA (GRID:grid.38142.3c) (ISNI:000000041936754X); Broad Institute of MIT & Harvard, Cambridge, USA (GRID:grid.66859.34) 
29  University of British Columbia, Department of Experimental Medicine, Vancouver, Canada (GRID:grid.17091.3e) (ISNI:0000 0001 2288 9830); University of British Columbia, Department of Pediatrics, BC Children’s Hospital, Vancouver, Canada (GRID:grid.17091.3e) (ISNI:0000 0001 2288 9830); Telethon Kids Institute, Subiaco, Australia (GRID:grid.414659.b) (ISNI:0000 0000 8828 1230) 
Publication year
2019
Publication date
Dec 2019
Publisher
Nature Publishing Group
e-ISSN
20411723
Source type
Scholarly Journal
Language of publication
English
ProQuest document ID
2190465674
Copyright
This work is published under http://creativecommons.org/licenses/by/4.0/ (the “License”). Notwithstanding the ProQuest Terms and Conditions, you may use this content in accordance with the terms of the License.