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.
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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.
Specially, differential expression of lncRNA FAM83H-AS1 was extremely significant ( P = 1.72E-101, fold change value = 3.781).
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 ).
Fisher exact test confirmed that the overlap between peaks lost in the IDH mutant tumors is highly significant (p<10 −100 ).
Nevertheless, the differences between the case groups (TIO and BM) and the control group (HC) were both extremely 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).
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).
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).
Observing such an intersection at random, under a uniform/independent null model, is highly significant (p-value < 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 ).
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.
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 ).
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 ).
All these variables have a statistically highly significant correlation (P~10 −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.
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.
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 highest enriched category for bQTL variants was “Myocardial infarction” and for caQTLs “CARDIoGRAMplusC4D” and “Coronary artery calcification.” clQTL variants were enriched for “Myocardial infarction,” “CardiogramplusC4D,” and the highly significant term “Coronary artery,” which was the second most significant category ( P < 10 −100 ) ranked by P value (Fig. 2 a–c).
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 result was highly significant (p<1×10 -100 ), with the largest overrepresentation coming from the case where both changed.
3c , upper panel; n = 3365; median CO = 0.68, IQR = 0.46–0.82), and the difference in median CO between positively responsive cells and the entire population of segmented cells ( n = 24,540; median CO = 0.44, IQR = 0.23–0.70) was highly significant ( P < 10 −100 , Wilcoxon rank-sum 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.