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

Ahwon Lee ,Amrit Singh,Guzmán Sanchez-Schmitz,Tobias R Kollmann,Jorjoh Ndure,G Saleu ,Alansana Darboe,Joann Diray‐Arce ,Daniel He,Kinga K Smolen,Samuel Sj Hinshaw ,Elishia Roberts,Ofer Levy,Davide Ferrari,Momoudou Cox,Robert Rew Hancock ,Hanno Steen,Peter Richmond ,Al Ozonoff,William Ws Pomat ,Simon Sd Van Haren ,Casey P Shannon,Ryan R Brinkman,Asimenia Angelidou,Reza Falsafi,Mehrnoush Malek,Tue Bjerg Bennike ,Anita Ahj Van Den Biggelaar ,Rebecca Ford,Wendy Kirarock,John Paul Matlam,Beate Kampmann,Cai Bing,Jainaba Njie-Jobe,Erin E Gill ,Nelly Amenyogbe,Olubukola Ot Idoko ,Daniel Dj Harbeson ,Kim‐Anh Lê Cao ,Geraldine Masiria,Scott Sj Tebbutt ,Rym Ben‐Othman ,Matthew Ma Pettengill

doi:10.1038/s41467-019-08794-x

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.

Highlights

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 profiled the peripheral blood of each participant twice over their first week of life, i.e. at Day of Life (DOL) 0 and at either DOL1, 3, or 7, and sought to identify variables that differed between the baseline and later time points across all participants
Based on the relevant univariate analysis, we found that plasma concentrations of C−X −C motif chemokine 10 (CXCL10), interleukin (IL)-17A, macrophage-derived chemokine (MDC), and interferon (IFN)γ increased, while IL-10, Chemokine C−C motif ligand (CCL) 5, granulocyte colony stimulating factor 2 (GCSF), and IL-6 decreased with age over the first week of life; many other soluble immune markers remained unchanged

Summary

Introduction

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. Systems biology approaches, employing highdimensional molecular and cellular measurements ( referred to as OMICs), along with unbiased analytic approaches, have increased our understanding of basal and altered molecular states in adults[3] and recently in newborns and infants after the first week of life[4,5], but such approaches have not been applied systematically to characterize molecular ontogeny over the most critical period, i.e. the first week of life[1] This is likely due to the analytical challenges posed by the limited amount of biosample that can be obtained[6,7,8] and the many rapid physiological changes around birth[1]. Despite the substantial variability between participants and these dramatic changes, ontogeny followed a robust trajectory common to newborns from very different areas of the world

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Conclusion