Excerpts

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 ).

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 ).

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 ).

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.

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

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

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).

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 ).

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.

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

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.

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.

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).

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 ).

When p was below the calculation limits of the software (highly significant) we noted p<1.0e−99*.

http://www.ncbi.nlm.nih.gov/geo/ ) data base indicates a highly significant anti-correlation with a gene signature obtained from primary human lung fibroblast treated with dithiothreitol (DTT) for 24 hours (Overlapping P = 1.7E-99) [ 63 ]; and a significant correlation with a gene set from dexamethasone-treated (24 hours) human primary osteoblast-like cells (HOb)(GEO series GSE10311 .Overlapping P = 1.0E-46).

The SNP-based heritability estimated on the observed scale was 0.78% (SE = 0.04%), which was highly significant (Z = 21.09, P-value = 9.41 × 10−99), further supporting a polygenic basis for ovarian cancer.

TH interneuron density increased steeply toward ventral caudoputamen ( β = 519.7, p = 5.6 × 10 −85 , N (hemispheres) = 13, N (sections) = 299), while SST interneurons showed a more moderate but highly significant ventral increase ( β = 253.9, p = 3.9 × 10 −98 , N (hemispheres) = 12, N (sections) = 276).

Additionally, the chi-square test for taxonomic distribution differences was highly significant ( χ 2 = 549.60, p < 7.64E-97), indicating that microbial composition varies between conditions.