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

Lee, AHORCID logo; Shannon, CPORCID logo; Amenyogbe, N; Bennike, TBORCID logo; Diray-Arce, J; Idoko, OT; Gill, EE; Ben-Othman, R; Pomat, WS; van Haren, SD; +34 more...Cao, KLORCID logo; Cox, M; Darboe, AORCID logo; Falsafi, R; Ferrari, D; Harbeson, DJ; He, DORCID logo; Bing, C; Hinshaw, SJ; Ndure, J; Njie-Jobe, J; Pettengill, MA; Richmond, PC; Ford, R; Saleu, G; Masiria, G; Matlam, JP; Kirarock, W; Roberts, E; Malek, M; Sanchez-Schmitz, G; Singh, AORCID logo; Angelidou, A; Smolen, KK; EPIC Consortium; Brinkman, RR; Ozonoff, A; Hancock, REORCID logo; van den Biggelaar, AH; Steen, HORCID logo; Tebbutt, SJORCID logo; Kampmann, BORCID logo; Levy, OORCID logo; Kollmann, TRORCID logo and (2019) Dynamic molecular changes during the first week of human life follow a robust developmental trajectory. Nature communications, 10 (1). 1092-. ISSN 2041-1723 DOI: 10.1038/s41467-019-08794-x
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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.


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