Department of Microbiology & Immunology, University of British Columbia, 1365-2350 Health Sciences Mall, Vancouver, BC, V6T 1Z3, Canada.
PROOF Centre of Excellence, 10th Floor, 1190 Hornby Street, Vancouver, BC, V6Z 2K5, Canada.
Nat Commun. 2019 Mar 12;10(1):1092. 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.
系统生物学可以揭示复杂的生物学，但尚未广泛应用于极易受到多种疾病影响的人类新生儿群体。我们优化了方法，以便从新生儿容易获得的 <1 毫升血液中提取转录组、蛋白质组、代谢组、细胞因子/趋化因子和单细胞免疫表型数据。对基线进行索引并应用创新的综合计算方法，可以揭示生命最初一周沿着一条非常稳定的发育轨迹发生的显著变化。这在干扰素和补体途径以及中性粒细胞相关信号的变化中最为明显。经过来自西非和澳大拉西亚的两个独立新生儿队列的验证，出现了一个稳健且常见的轨迹，这表明存在一种有目的而非随机的发育路径。系统生物学和创新的数据集成可以为生命最初一周的分子发生提供新的见解，这是一个动态的发育阶段，对健康和疾病至关重要。
