Excerpts

The top five ranked interlinked pathways (Supporting Information Table S5 ) and the three Gene ontology (GO) molecular function terms (Supporting Information Table S6 ) are highly significant ( p ≤10 −27 ) with respect to genes differentially expressed after RPL19 knockdown.

Above all, in all GO analyses there was a highly significant enrichment in the term ‘testis’ for the tissue category (p < 10 −27 ), indicating that most DE coding genes that are co-expressed with lncRNAs along spermatogenesis are testis-specific.

However, stratification by isoform into LMW (at least one isoform with 10–22 KIV repeats) and HMW (only isoforms with >22 KIV repeats) carriers, revealed a highly significant decreasing effect of rs41272110 in LMW carriers (β = –24.28, p = 1.05e-27), which was not seen in HMW carriers, where it presented rather a small but significant Lp(a)-increasing effect (β = +1.69, p = 6.13e-07).

The differences in proportions with ≥ 1 APOE ε4 allele were highly significant ( p = 1.5 × 10 −27 ).

Differences between the two groups were highly significant (p = 1.5×10 −27 ).

This 4.4% decrease in lifetime is highly significant (P = 1.6 × 10 −27 ).

The discrimination capacity of the model was high (AUC = 0.811) and highly significant ( p = 1.782 × 10 –27 ).

The results of this analysis, following removal of outliers, revealed a highly significant effect of the mutation type (specifically splice-site mutations) on the number of CALs, both with 1 to 5 CALs ( p = 1.8 × 10 −27 ) and 6 to 99 CALs ( p = 8.5 × 10 −43 ), as well as for skin freckling ( p = 0.028) and neoplasms ( p = 0.006).

Association analysis revealed a highly significant association between rs13292899 and NSCL/P risk ( p = 1.85 × 10 −27 ) [ 73 ].

These analyses also further revealed highly significant associations for the MRPS18C isoform uc003hor ( P = 1.94x10 -27 and r 2 = 0.143) (Figure 6E ).

In addition, we identified highly significant missense variants (<5 × 10 −15 ) within the FLG gene (rs558269137, beta = −0.222, p = 1.96 × 10 −27 ) and the KRT1 gene (rs14024, beta = −0.030, p = 3.95 × 10 −15 ).

The samples clustered into two distinct and well-separated classes, and evaluation of the model showed that it was highly significant ( p = 2.3E −27 permutations p = <0.001).

We detected approximately 15.000 transcripts in the ventricles and surprisingly, within the TAD only Scn5a expression was highly significant downregulated ( P = 3.75e-27) in RE6-9 +/− mice (Fig. 4c–f ).

Two-way ANOVA revealed a highly significant difference between the two cell lines ( p = 4.68 × 10−27), indicating a strong overall effect of cell type on the outcome (partial η2 = 0.484).

Gene ontology term analysis for the training response also revealed a highly significant over-representation of neurological processes ( Neurological system process: P = 4 .85 × 10 −27 , Cognition: P = 1.92 × 10 −22 , Sensory perception: P = 4.21 × 10 −21 ) and the extracellular region ( Extracellular region: P = 1.40 × 10 −10 ).

This difference was highly significant by both parametric (Welch’s t = 11.40, p = 4.98 × 10 −27 ) and non-parametric (Mann-Whitney p = 3.59 × 10 −19 ) tests, with a large effect size (Cohen’s d = 1.14).

The average difference in TraP scores between the groups is highly significant (0.62 vs. 0.078, pathogenic versus benign variants, respectively, MW-test, P -value = 7.1 × 10 −27 ).

Remarkably, there was a highly significant overlap ( P = 7.29E–27) between genes affected at gene expression and splicing level (391, 42.6%; Figure 2C ).

Interestingly, we found a highly significant dependency of FCER1A expression on GATA-2 transcript levels (p = 7.8×10 −27 ).

This was highly significant ( χ 2 =97.3, P <10 −26 ).

Figure 5 D illustrates the large degree of overlap between wild-type LD and wild-type DD oscillators, a highly significant (Fisher's exact test p < 10 −26 ) and unsurprising result, considering the extensive program of circadian expression that is detected in combined wild-type LD + DD data ( Figures 2 A, 2 C, 3 A, and 5A).

A similar analysis performed between populations from Libreville and either of the village and sylvatic LLP areas shows highly significant differences ( p ‐value < 10 −26 for each test; Figure S7 ).

Non-parametric Kruskall–Wallis tests confirm that these differences are highly significant, both for the pRF eccentricities (Chi square = 126.9; p < 10 −26 ) and for their sizes (Chi square = 122.0; p < 10 −25 ).

The model achieved a highly significant separation of the overall survival ( p < 10 −26 , c = 0.65 ± 0.02, Fig. 2 b), with distinct survival trajectories across the three clusters.

S3A), but the overall altered profile was highly significant ( P = 10 −26 , Fisher exact test in comparison with the ∼8,000 genes expressed).