Excerpts

For a random protein set of comparable size, the expected number of edges was 8, whereas the observed network contained 44 interactions, resulting in a highly significant PPI enrichment p -value < 1.0 × 10 −16 .

Furthermore, we validated rhythmicity using two alternative detection methods [RAIN (Thaben & Westermark, 2014 ) and ARSER (Yang & Su, 2010 )], which showed a highly significant overlap between the groups ( Appendix Fig S1G ; two‐sided Fisher's exact test, P < 10 −16 for every pairwise comparison).

Overall, a test of independence between the risk score tertiles and the potentially AAMR CNV count classes shows a highly significant association ( P < 1 × 10 −16 ) for both Fisher's exact test and a χ 2 test.

One-way analysis of variance (ANOVA) using the cluster size as the factor variable found that both results are highly significant ( P < 10 −16 ).

Across all 10‐kb windows in the genome, there was a weak but highly significant correlation in the distribution of Tajima's D values in the two clusters (Figure 4 b; Spearman's ρ = 0.25; p < 10 −16 ).

Using STRING analyses, we identified a highly significant protein–protein interaction (PPI) enrichment ( P = 10 −16 ) only for the downregulated genes of H2A.Z.1‐depleted cells.

The differences between benthic and pelagic species in both measures were highly significant (P ~ 10 -16 ).

The expected number of edges is 393 and has a PPI enrichment p -value was highly significant ( p < 10 −16 ).

In comparison, full-field static flashes were represented by waveforms that were 147 ± 4% and 115 ± 2% of the full-field motion responses in the two populations; this difference in the ratio between responses to stationary flashes and full-field motion was highly significant ( p < 10 −16 , Fig. 2e ).

However, while the difference between term and moderate to late preterm TREC was significant but not meaningful, 108 (70–170) vs 101 (64–164) median TREC ( p = 0.0017), the differences between term and extremely preterm, 49 (29–92), or very preterm, 88 (52–149), were both highly significant ( p = 1E −16 , p = 4E −6 , respectively) and meaningful.

After removal of disconnected nodes, the refined network consisted of 267 nodes and 1154 edges, with an average degree of 8.64 and a highly significant PPI enrichment ( P < 1.0e-16).

The PPI network showed a highly significant enrichment with a p-value of <1.0e −16 and an average local clustering coefficient of 0.707.

The resulting network comprised 14 nodes and 87 edges with a highly significant enrichment (p-value <1.0e–16), indicating nonrandom functional connectivity among apoptosis, inflammation, and oxidative-stress regulators.

The difference between the two distributions was highly significant ( p < 10 −16 , two-sided Wilcoxon rank-sum test).

Indeed we observed for all species a highly significant correlation between GC content and thermodynamic stability and folding strength (Spearman’s rho =0.239, p -value <10 -16 for all lincRNAs considering folding strength) as observed in [ 49 ].

For the secretome of ET-eMSC, the enrichment of low and high abundance proteins was highly significant ( p < 10 −16 ).

Moreover, using paired t tests to validate these differences, we found highly significant differences between the observed distributions of FD and PD and the null models ( P < 10 −16 , t test).

Enriched Biological Networks A total of 1311 unique protein targets were submitted to the STRING database for network enrichment analysis, yielding a highly significant PPI enrichment p -value < 1.0 × 10 −16 ( Supplementary File Sheet S13 ).

The discovery and validation gene counts were 2.8 and 1.2 enriched respectively in the 38 Cluster 2-like NPH astrocytes and highly significant (chi-square test of expected versus observed UMIs; p < 1E-16).

Interaction network and functional enrichment of differentially abundant proteins The interaction network between the DAPs was highly significant (p-value < 10 −16 ), indicating that the DAPs are at least partially biologically connected (Fig. 2 ).

Notably, the results of this analysis showed that the majority of the proteins (73 of the 81 submitted proteins) are connected within a single network, with a highly significant protein-protein interaction enrichment (p-value < 10 −16 ) (Fig. 1A ).

The resulting network comprised 308 nodes and 3649 edges, with an average node degree of 23.7, a local clustering coefficient of 0.494, and a highly significant PPI enrichment p -value < 1.0 × 10 −16 , indicating robust protein–protein associations beyond random expectation ( Figure S2 ).

The network demonstrated highly significant connectivity (PPI enrichment p -value < 1 × 10 −16 ), as 201 interactions were observed compared to the 27 edges expected by chance, supporting functional relationships among the proteins rather than random connectivity.

STRING analysis revealed a highly significant enrichment of protein–protein interactions (PPI enrichment p < 1.0 × 10 −16 ), confirming that the identified proteins are functionally connected rather than randomly associated.

This evidence of highly significant PPIs (actual edges = 1015, expected edges = 405, P < 1.0 × 10 −16 ) and highly ASD-relevant GO BP enrichment showcases a clear example of how the PFC sex*genotype DE genes are embedded within a complex systems-level biological pathology that integrates abnormalities along these key processes and pathways.