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Lee, Amy H.; Shannon, Casey P.; Amenyogbe, Nelly; Bennike, Tue B.; Diray-Arce, Joann; Idoko, Olubukola T.; Gill, Erin E.; Ben-Othman, Rym; Pomat, William S.; Van Haren, Simon D.; Cao, Kim-Anh Le; Cox, Momoudou; Darboe, Alansana; Falsafi, Reza; Ferrari, Davide; Harbeson, Daniel J.; He, Daniel; Bing, Cai; Hinshaw, Samuel J.; Ndure, Jorjoh; Njie-Jobe, Jainaba; Pettengill, Matthew A.; Richmond, Peter C.; Ford, Rebecca; Saleu, Gerard; Masiria, Geraldine; Matlam, John Paul; Kirarock, Wendy; Roberts, Elishia; Malek, Mehrnoush; Sanchez-Schmitz, Guzman; Singh, Amrit; Angelidou, Asimenia; Smolen, Kinga K.; Brinkman, Ryan R.; Ozonoff, Al; Hancock, Robert E. W.; Biggelaar, Anita H. J. van den; Steen, Hanno; Tebbutt, Scott J.; Kampmann, Beate; Levy, Ofer; Kollmann, Tobias R.; Vo, Diana; Kraft, Ken; McEnaney, Kerry; Vignolo, Sofia; Marchant, Arnaud (2019): Dynamic molecular changes during the first week of human life follow a robust developmental trajectory. In: Nature Communications, Vol. 10, 1092
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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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