“highly significant”

Unusually, ChIP-seq identified highly significant, noncanonical binding of DsdC1 FLAG ( P = 1.98 × 10 −106 ) and DsdC2 FLAG ( P = 2.5 × 10 −74 ) both within the coding sequence and directly downstream of the neuO gene, with only a very modest peak being identified within its promoter region ( Fig. 4 A ).

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 ).

Despite these differences, mRNA and protein levels displayed a highly significant positive Pearson’s correlation coefficient of 0.35 ( p = 3.6 × 10 −104 Figure 1 a).

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 ).

For example, when considering the 100 top genes most enriched in a cell type, there was a highly significant enrichment in astrocytes (Fold Enrichment (FE) = 1.4e8, p = 4.2e-103), endothelial cells (FE = 1.2e8, p = 2.8e-86), microglia (FE = 1.2e8, p = 2e-86), neurons (FE = 4.2e7, p = 3.7e-30), and oligodendrocytes (FE = 2e8, p = 6.4e-163) across the five data sets.

We also confirmed strong and highly significant associations at the previously described loci, including chromosome 2q24.2 encoding PLA2R1 (rs17831251, OR = 2.25, Meta-analysis P = 4.7 × 10 −103 ) and 6p21.32 encoding HLA-DQA1/DRB1 genes (rs9271573, OR = 2.41, Meta-analysis P = 2.7 × 10 −154 ).

This highly significant overlap ( p -value = 4.3 × 10 − 102 by hypergeometric test, 2.4-fold-enriched) demonstrates that alteration of regulatory complex binding is strongly predictive of a change in gene expression (i.e., 70%; 359 / 510) and suggests possible mechanisms for the observed gene expression effects.

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.

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

Comparing fold-changes, we found a highly significant positive correlation between the bulk RNA-seq and the F-Cyc and F-CI populations (Additional file 2 : Figure S6A,B; Spearman’s correlation test; p <1×10 −100 ).

As expected, these region-specific inflammation gene networks (HIP_M18, TCx_M18, PCx_M18, FWM_M13) show highly significant gene overlap (hypergeometric test, p<10 −100 ), despite being generated independently.

This corresponds to a 20-fold enrichment and is highly significant ( p <1.0E-100).

Indeed, as shown in Fig 3A and 3B , the correlation between the time-delayed evidence and the value of PC2 is highly significant ( p < 10 −100 ) with a correlation coefficient of R = 0.92.

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 ).

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.

Notably, DNMT3A2 -exon expression in AML patients revealed a highly significant correlation with DNAm levels at CpGs that were hyper- and hypomethylated upon KD of transcript 2 in vitro ( P < 10 −100 and P = 2 × 10 −37 , respectively; Fig 4B ).

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

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.

The ANOVA statistical difference between the expression levels of the HLA loci was highly significant ( P < 1.0 × 10 −100 ).

A very interesting observation is the highly significant ( p < 10 −100 ) reduction of the expression variability in the cancer nodules with respect to the normal tissue.

Observing such an intersection at random, under a uniform/independent null model, is highly significant (p-value < 10 −100 ).