“highly significant”

Therefore, we calculated the statistical probabilities of two-way overlap between exosome and CP190, BEAF-32 or CTCF sites by hypergeometric tests considering only active TSSs of all annotated gene isoforms and indeed observed highly significant overlap over expectation ( P < 3.7 × 10 − 110 for each comparison).

Since the A and flanking C1 and C2 exons constitute only a small portion of the coding genome (∼10 million nucleotides as per our dataset), this enrichment is highly significant as revealed by a Chi-square test (P<1.99e-108), when comparing the ratios of driver vs. passenger mutations in alternative splicing neighborhoods as compared to the rest of the exome.

As anticipated, lipid ratios capturing PUFA synthesis, namely PE(P-16:0_18:2)/PE(P-16:0_20:4), PE(P-18:0_18:2)/PE(P-18:0_20:4), PE(P-16:0_18:3)/PE(P-16:0_20:5) and PE(P-18:0_18:3)/PE(P-18:0_20:5), exhibited highly significant associations with FADS1/FADS2/FADS3 loci [575 SNPs; top hit: rs174564 for the PE(P-18:0/18:2)/PE(P-18:0/20:4); imputation r 2 = 0.999; beta = 0.49; p-value = 8.07 × 10 −107 ; p-gain = 2.60 × 10 +83 ].

We found that 48% (237/489) of Hoxa2-regulated genes had at least one Hoxa2-bound region assigned to them, which represents a highly significant enrichment compared with all genes ( P = 1.1 e –106) ( Figure 4 A).

Bioinformatics analysis of training cohorts identified a 61-gene signature that was highly significantly associated with RFS (HR = 37.08, P = 2.68*10 −106 , sensitivity = 89.29%, specificity = 89.61%, and AUC = 0.937).

Using these analytic approaches, we found that each of the eight groups of sex-specific genes listed in SM- Table 3 a-3b are jointly and significantly associated with longevity in one sex ( P = 8.7 × 10 −165 ∼1.5 × 10 −37 ), but not jointly significant in the other sex ( P > 0.05), while PRS-sex interaction effects are highly significant ( P = 5.2 × 10 −106 ∼4.4 × 10 −15 ) (SM- Table 5 ).

S2 ): While only 24,303 (5.7%) of the total 427,350 pairs of enzyme-catalyzed reactions are coregulated, 175 (42.9%) of the 408 fully coupled pairs are coregulated, which is highly significant (hypergeometric test, P value = 4.2 × 10 −105 ).

Next, based on the z score in the latent factor mixed models (LFMMs), we detected 155 CNVs with |z| scores ≥ 10 ( Supplementary Table S11 ) that were highly significant (3.63 × 10 −6 ≥ p values ≥ 1.34 × 10 −103 ), associated with environmental parameters in 47 old sheep populations.

Among these, MTND2 had highly significant associations across HDL cholesterol, Apolipoprotein A1, LDL and Triglycerides (lowest P = 3.2 × 10 –103 ).

The 212 transcripts reduced in both Caco2 and HUG1N cells depleted of GATA6 represent a highly significant, non-random overlap ( Fig. 4A ; odds ratio 9.0, p <4 × 10 −103 by Fisher exact test) and were enriched for Gene Ontology terms related to the cell cycle, particularly M-phase ( Fig. 4B ).

Other highly significant proteins for AD included GFAP ( β = 0.676; FDR-adjusted p = 5.02 × 10 −102 ), p-tau231 ( β = 0.700; FDR-adjusted p = 4.42 × 10 −94 ), NEFL ( β = 0.417; FDR-adjusted p = 1.52 × 10 −48 ) and p-tau181 ( β = 0.483; FDR-adjusted p = 9.25 × 10 −46 ; Supplementary Table 1 ).

Considering the pool sizes ( N = 651 and N = 240 for thapsigargin stimulation and nutrient starvation, respectively), this intersection was found highly significant ( p = 1.44×10 -101 ), thus showing that a strong common transcriptional signature exists for genes upregulated by these two stresses.

This comparison yielded a highly significant overlap ( P < 1e−100) in 2419 of 3802 DEGs, validating our adopted strategy ( supplemental Figure 1 D).

Similarly, when surveying combined protein expression and SV data across 328 cell lines 38 , 54 , 55 , we observed a highly significant overlap ( p < 1E−100 chi-square test) of events involving CRISPR knockout effect in genes with events involving SV-associated protein over-expression (Fig. 8b ), involving 2682 genes, 178 with combined breakpoint and protein over-expression involving at least 5% of cell lines examined (Supplementary Dataset 10 ).

Indeed, the latter method produces a highly significant correlation (σ = 0.97, p < 10 −100 ) between the number of afferent and efferent partners of each cell.

All these variables have a statistically highly significant correlation (P~10 −100 ).

Fisher exact test confirmed that the overlap between peaks lost in the IDH mutant tumors is highly significant (p<10 −100 ).

The reduction in likelihood caused by eliminating one of the pause states was highly significant, and cannot be attributed simply to the elimination of two parameters ( p <10 -100 ; likelihood ratio test).

We found that the similarity among all pairs of networks was highly significant (hyper-geometric test P -value <10 −100 ), and hence we focused on the F -score as this was a more sensitive measure for comparisons.

The likelihood ratio test further indicated that the genetic effect was highly significant (LRT = 1,655.76, df = 1, P < 10 −100 ) ( Kang et al., 2008 ; Yang et al., 2011 ; Visscher et al., 2008 ).

There was highly significant overlap (at empirical p < 10 −100 , see Methods for permutation procedure) between the DERs and histone marks associated with active chromatin, including H3K36me3 (OR=13.32), H3K4me1 (OR= 3.00), H3K4me3 (OR=5.66), and H3K9ac (OR=4.82).

A more detailed analysis reveals that a clear and highly significant ( p < 10 -100 , Wilcoxon rank sum test) difference is seen between the mean of the CP M sc ( M ̄ s c = 0.19 ± 0.30) and the mean of the negative sequence M sc ( M ̄ s c = 0.02 ± 0.09).

Gender and age Even after exclusion of sex-linked genes, gender was independently associated with the largest number of expression traits ( n = 31) which, considered all together, contributed to a highly significant discrimination between males and females ( P <10 −100 ).

Likelihood ratio tests indicated a highly significant genetic effect (LRT = 197.9, df = 1, P < 10 -100 ), suggesting that approximately 70% of the phenotypic variation is attributable to genetic factors.

Remarkably, of the 1733 proteins in our data set, 62% were elevated significantly in at least one mutant (62% was highly significant in comparison to the null hypothesis in which peptide ratios are randomly assigned to proteins ( p value < 1e-100)), suggesting that the Cdc48 network has a profound impact on the UPS that is greater than has been previously appreciated.