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Integrated Blood Analysis Offers Look at Immune Development Over Infants' First Week

NEW YORK (GenomeWeb) – A new systems biology study has uncovered reproducible blood gene expression, metabolomic, and proteomic profiles in newborn babies as they encounter bacteria and viruses during their first week of life — including immune response insights that are expected to aid in future antibiotic and vaccine studies.

"This common trajectory is exciting as it allows us to ask bigger questions about the differences between different populations and the impact of biomedical interventions such as vaccines on development," co-senior and co-corresponding author Ofer Levy, director of Boston Children's Hospital's precision vaccines program and a Harvard Medical School researcher, said in a statement.

As part of the international effort, he and his colleagues brought together RNA sequencing-based gene expression analyses, blood metabolomic patterns generated by tandem mass spectrometry, proteomic profiles, single-cell immune phenotyping insights, and other data collected over up to one week in 30 newborns in Gambia. Their integrated bioinformatic analyses pointed to "dramatic changes along a remarkably stable developmental trajectory over the first week of life."

The team subsequently validated those findings with samples from another 30 infants from Papua New Guinea. From these and other results, the investigators speculated that it may be possible to tap into early infant immune responses when designing new vaccines and gauging the immune responses spurred on by existing vaccinations.

"Our data represent the most comprehensive systems biology study yet performed during the first week of human life," the authors wrote in their new Nature Communications study. They noted that "contrary to the relatively steady-state biology observed in healthy adults, the first week of human life is highly dynamic."

For their analyses, Levy and his colleagues collected small peripheral blood samples from 30 newborns in Gambia. They obtained a second sample from each infant at one, three, or seven days of age, making it possible to generated transcriptomic, proteomic, metabolomic, and immune cell composition profiles for 10 of the infants at each time point.

"One of the objectives of this project was to develop a robust standard operating protocol to enable extraction and analysis of data using systems biology (big data) approaches from small blood sample volumes that can readily be obtained for research purposes from newborns within the first week of life," the authors explained.

The team integrated the data using a biological function-based NetworkAnalyst method, a "Data Integration Analysis for Biomarker discovery" (DIABLO) approach, and a multi-factorial response network to get a look at the functional network — along with the expression, protein, and metabolite trajectories — at play in each infant and across the group over a week.

In the process, the investigators identified immune cell types, immune pathways, and other functions that rise and wane in the first seven days for the Gambian infants profiled, and for 30 additional newborns from Papua New Guinea. The analysis highlighted an uptick in Toll-like receptor signaling, NOTCH signaling, and other host defense pathways, for instance, and provided a look at the development of infants' interferon signaling, complement cascade, and neutrophil pathway activity.

"Our approach and the resulting observations will serve as a crucial backdrop for future studies that characterize the impact of a broad array of factors, including genetics, epigenetics, maternal influences, microbiota, diet, and disease, as well as chemical and biochemical interventions such as antibiotics and vaccination," the authors concluded.

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