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

人类生命第一周内的动态分子变化遵循稳健的发展轨迹

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作者: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, Jor

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.

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