Fig. 6

Independent validation and data meta-integration of the robust developmental trajectory during the first week of life. Generalizability of the multivariate integrative model (DIABLO) depicted in Fig. 5 based on data from Gambian newborns was evaluated by assessing its ability to classify DOL from OMICs profiles in a new set of validation samples collected from newborns from a second site (Papua New Guinea (PNG)). a Pathway enrichments of Molecular Interaction Networks Integration, DIABLO and MMRN identified congruent functional pathways of the first week of life. b The dashed line corresponds to the 95% confidence level ellipses for the scores obtained from the Gambia training data. Samples from the PNG site generally resided within the correct ellipse, demonstrating good agreement between actual DOL and DOL as predicted by the model. Similar figures were generated for other OMICs data (Supplementary Figure 10). c This agreement was quantified using area under the receiver operator characteristics curve (AUROC) analysis comparing DOL0 (red), 1 (blue), 3 (green), and 7 (purple) individually vs. all other DOLs combined. d shows zero-order interaction networks for DOL7 vs. DOL0 containing nodes for transcriptome (blue), proteome (green), metabolome (red), and DIABLO-selected features (purple). Genes involved in the interferon and complement pathways and neutrophil degranulation are highlighted by the orange boxes. e−g Relative abundance of a selected subset of markers identified by DIABLO are shown for each DOL for both the Gambian cohort, on which the model was trained, and the validation cohort from PNG. The cells (flow cytometry; FC), plasma cytokines (Luminex assay; CYT) and plasma proteins (mass-spectrometry proteomics; PROT), transcripts (RNA-Seq; RNA), and metabolites (mass-spectrometry metabolomics; META) identified by DIABLO were associated with interferon signaling (e), neutrophil recruitment and activation (f), and complement pathways (g). The differences observed between DOLs in the Gambia cohort were generally replicated in the PNG cohort. Boxplots display medians with lower and upper hinges representing first and third quartiles; whiskers reach the highest and lowest values no more than 1.5× interquartile range from the hinge ****p ≤ 0.0001, ***p ≤ 0.001, **p ≤ 0.01, *p ≤ 0.05, ns p > 0.05, by ANOVA. DIABLO: Data Integration Analysis for Biomarker discovery using Latent cOmponents, DOL: day of life, MMRN: multiscale, multifactorial response network