41 All clocks demonstrated a strong and highly significant correlation with the biologic age, with the skin and blood clock demonstrating the strongest correlation (Pearson R = .96; 95% CI, 0.959–0.97; P <1 × 10 16 ) ( Figure 8 A ).
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The C > A mutations observed were associated with highly significant sequence-selectivity, being marked by an excess at CpCpT (NGCII082, odds ratio (OR) = 3.2, P -value < 10 -16 , χ 2 test) or TpCpA sites (NGCII092, OR = 1.7, P -value < 10 -16 , χ 2 test) and extensions of these motifs (Materials and methods; Note 6 and Figure S6 in Additional file 1 and Table S14 in Additional file 6 ).
In other words, organisms sampled from a defined skin habitat were more similar to each other in 16S sequence than expected for a global background; this enrichment was statistically highly significant (p<<10 −16 , one-sided Mann-Whitney-U test, see Table S1 ).
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 ).
For our list of 64 miRs, 18 enrichment pathways are highly significant ( p < 1E-16).
This overlap is highly significant ( P -value <10 −16 , hypergeometric test where the intersection is 9000 between 700 000 conserved islands and 60 000 DHSs, assuming a total of 30 000 000 potential loci), consistent with the idea that sequence conservation at overlapping unannotated conserved island/DHS loci reflects the importance of regulatory factor binding to DNA.
The difference in degree of nucleotide conservation between the IDR and the remainder of the molecule is highly significant ( P <10 −16 ), and indicates a dramatically higher level of divergence for the IDR-encoding portion of the mammalian TS transcript.
It further confirmed that the association of clock PRRs with flowering control genes was not random and connected with a highly significant value of p < 1 × 10 −16 .
ChIP-seq showed there was a highly significant correlation ( p values < 10 −16 ) between ER binding fold changes induced by the addition of elacestrant or fulvestrant in the three cell lines tested (Pearson correlations with p values <10 −16 ; 0.78 MCF7, 0.47 MCF7-LTED wt and 0.60 MCF7-LTED Y537C ) especially in regions where there was increased ER binding after treatment versus E2 (Fig. 4A ).
The regression itself was highly significant ( R 2 = 0.93, P < 10 −16 ), and outliers were those points lying above or below a 99.9% confidence interval around the line of best fit.
This enrichment in interactions was further supported by a highly significant PPI enrichment p -value of <1.0 × 10 −16 , indicating that the proteins in our network have more interactions among themselves.
This difference between MS patients and non-MS controls is highly significant ( p < 10 − 16 ) .
The PPI network exhibited a highly significant enrichment, with a p-value of <1.0e-16 and obtained from a random set of proteins which is a distinguishable property of STRING analysis, suggesting that these proteins are more interconnected than expected by chance, pointing to their potential roles in Parkinson’s disease pathology ( Figures 3 , 4 ).
It exhibits highly significant protein interaction enrichment ( p < 1 × 10 −16 ).
Moreover, the Pearson correlation between association strength of shared SNPs across the two tissues was highly significant ( P <10 −16 ), highlighting the conservative genetic architecture of C18∶1, C18∶3, C20∶0 and C20∶1 in the two tissues.
Of these, 1495 genes are detectably expressed in our lines, and 1079 (72.2%) are classified as DE between the species in both data sets (a highly significant enrichment; χ 2 p < 10 −16 ).
Changes in mean activation magnitude in both regions between unscaled and scaled t-values are of the order of 10% of unscaled activation magnitude and are highly significant (a t-test over all voxels yields a p-value of p < 10 − 16 ).
The difference in the maximum likelihood (ML) values for the GTR + Γ and JC models was very large (Δln L = 14757.9) and highly significant ( P < 10 −16 ).
The overlap between our set of 2,407 genes and this set of 1,092 genes was highly significant (p<1x10 16 , Fisher’s exact test, S2B Fig ) and, since RNA-seq is typically more sensitive than microarray analysis [ 31 ], we proceeded with the larger gene set.
By comparing the joint mt / apico haplotype frequencies ( Supplementary Table 3 ), we found that the dependence between mt and apico was highly significant ( χ 2 =64,921, d.f.=39,566, P <10 −16 ), providing strong evidence of co-inheritance of the two organelles.
When we compared RtAI and the number of HGT events of each COG (again controlling for the fact that some genes appear in fewer organisms; see ‘Materials and Methods’ section) we, once more obtained a highly significant correlation ( r = −0.4125 and P < 10 −16 , pe < 0.001; n = 917).
In spite of different cell death phenotypes of these mutants, RNA-seq revealed that all three mutants down-regulated the same 95 genes and up-regulated the same 9 genes, a highly significant portion of the total transcriptome (p<10 −16 ) ( Figure 5 and Table S5 ).
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.
The perfect association of the haplotype was highly significant (p<10 −16 ).
A highly significant correlation (half-life: Spearman's r = 0.67, P ≤ 1e -16 ; decay rate: r = 0.64, P ≤ 1e -16 ) was obtained, supporting the initial finding that RNA stability becomes more pronounced with increasing distance from the promoter.