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


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.

SUBMITTER: Lee AH 

PROVIDER: S-EPMC6414553 | biostudies-literature | 2019 Mar

REPOSITORIES: biostudies-literature

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

Lee Amy H AH   Shannon Casey P CP   Amenyogbe Nelly N   Bennike Tue B TB   Diray-Arce Joann J   Idoko Olubukola T OT   Gill Erin E EE   Ben-Othman Rym R   Pomat William S WS   van Haren Simon D SD   Cao Kim-Anh Lê KL   Cox Momoudou M   Darboe Alansana A   Falsafi Reza R   Ferrari Davide D   Harbeson Daniel J DJ   He Daniel D   Bing Cai C   Hinshaw Samuel J SJ   Ndure Jorjoh J   Njie-Jobe Jainaba J   Pettengill Matthew A MA   Richmond Peter C PC   Ford Rebecca R   Saleu Gerard G   Masiria Geraldine G   Matlam John Paul JP   Kirarock Wendy W   Roberts Elishia E   Malek Mehrnoush M   Sanchez-Schmitz Guzmán G   Singh Amrit A   Angelidou Asimenia A   Smolen Kinga K KK   Brinkman Ryan R RR   Ozonoff Al A   Hancock Robert E W REW   van den Biggelaar Anita H J AHJ   Steen Hanno H   Tebbutt Scott J SJ   Kampmann Beate B   Levy Ofer O   Kollmann Tobias R TR  

Nature communications 20190312 1


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 traject  ...[more]

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