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

• Published in: Nature communications Vol. 10; no. 1; pp. 1092 - 14
• Main Authors: 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 Lê, 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, Guzmán, Singh, Amrit, Angelidou, Asimenia, Smolen, Kinga K., Brinkman, Ryan R., Ozonoff, Al, Hancock, Robert E. W., van den Biggelaar, Anita H. J., Steen, Hanno, Tebbutt, Scott J., Kampmann, Beate, Levy, Ofer, Kollmann, Tobias R.
• Format: Journal Article
• Language: English
• Published: London Nature Publishing Group UK 12.03.2019; Nature Publishing Group; Nature Portfolio
• Subjects: 38; 38/91; 49/31; 631/136; 631/1647/2067; 631/1647/320; 631/250; 631/553/2701; 82/58; 96/21; Biology; Blood; Chemokines; Chemokines - blood; Child Development - physiology; Cohort Studies; Computer applications; Cytokines - blood; Data integration; Gambia; Gene Expression Profiling; Humanities and Social Sciences; Humans; Immunophenotyping; Infant, Newborn - blood; Infant, Newborn - immunology; Interferon; Metabolomics; multidisciplinary; Neonates; Ontogeny; Papua New Guinea; Phenotyping; Proteomics; Science; Science (multidisciplinary); Systems Biology; Trajectories; Gambia; Papua New Guinea
• ISSN: 2041-1723; 2041-1723
• DOI: 10.1038/s41467-019-08794-x

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.