Excerpts

(Of note, the EMN estimation was repeated across different p value thresholds [i.e., defined as the limit of the top 0.5% p values and top 0.3%], obtaining consistent results across all thresholds, with strong highly significant correlations with the original EMN values [all r ~ 0.84, p < 10 −30 ].) Next, taking the 7718 values as data, we used a novel contrastive trajectories inference (cTI) algorithm to aggregate the DNAm data by identifying the trajectories of individuals aligned/ordered with the severity of epigenetic alterations hypothetically associated with maternal neglect.

In areas where the absolute value of log2FC was larger than 2, highly significant genes (-log10( p -value) > 30) were primarily enriched, suggesting a high degree of consistency in differential expression patterns across various data sources.

Thus, we used HOMER analysis for known motifs, revealing highly significant consensus motifs such as NRF1 ( P = 10 −30 ) and ZBTB33 ( P = 10 −24 ) ( Fig S6A ).

Suppression of PAPD4 also led to a highly significant reduction in miRNA expression, (t-test adjusted p value <1×10 −30 ), although the median relative miRNA expression value of 0.71 in siPAPD4 cells was of a smaller magnitude than observed from TUT1 suppression.

For example, Pfam domains exhibit a highly significant, negative correlation between domain promiscuity (see Methods ) and sequence identity (ρ = −0.21, p = 2.08 e −30 , Spearman test).

Functional analysis also implicated olfactory activity as a highly significant ( P = 2.310 × 10 –30 ) function of the top 100 most saturated downregulated genes.

In contrast to the above mutation hotspots, phosphosites in TP53 termini appear as highly significant mutation deserts (three pSNVs observed, 67±8 expected, P =2.8 × 10 −30 from ActiveDriver).

Specifically, M186 was enriched (Adj p = 3.8e−03) for class-switched memory B cells ( BANK1 , IGHA2 , PAX5 , and SPIB ), whereas M181 showed highly significant enrichment (Adj p = 3.6e−30) for plasma cells ( FCRLA , HERPUD 1, JCHAIN , MZB1 , TNFRSF17 , and multiple V region genes).

The model demonstrated a good fit (Pseudo R 2 = 0.4949) and a highly significant overall model effect (Log-Likelihood Ratio [LLR], p = 4.691e-30), supporting the robustness of these predictors.

Expression level correlation between milk cell miRNAs and skim milk miRNAs The average miRNA expression levels correlated between MC and SM with a highly significant (p = 4.8 E-30) correlation coefficient of 0.795 ( Fig 2A ).

The GWAS gave a highly significant peak for the ss2019324576 variant ( P -value = 6.436e-30, after Bonferroni correction for multiple testing), whereas all other SNPs were not significant ( P -value > 0.05, after Bonferroni correction for multiple testing).

We found a highly significant correlation between the Magenta module eigengene (based on 76 probes) and strain status ( r = 0.99, p < 1.0e-29).

The increase in correlation coefficient is highly significant ( p -value < 10 -29 ) (Materials and Methods), arguing that our non-linear correction to the whole proteome abundances has increased the accuracy of these estimates.

The correlation was highly significant ( ρ = 0.7304, p < 10 −29 ) and within this set the outliers (points which depart from the diagonal) were pairs of words relating apple to other concepts: apple-orange, apple-green, and apple-salad, which are more similar in Spanish than in English.

The enrichment of 15q13.3 microdeletions within neurodevelopmental disorder-affected and ASD-affected case subjects (0.4% combined in NDD and ASD case subjects; 0.004% in control subjects) is highly significant (p < 1.30 × 10 −29 ).

In total, 15 lifestyle factors were observed to interact with GS BMI , of which alcohol intake frequency, usual walking pace, and Townsend deprivation index, a measure of socioeconomic status, were all highly significant ( p = 1.45*10 −29 , p = 3.83*10 −26 , p = 4.66*10 −11 , respectively).

We found a highly significant replication (mean R 2 = 0.07; P = 1.5 × 10 −29 ), explaining 41% of in-sample cross-validation R 2 (Supplementary Figure 3 ), which is consistent with previous out-of-sample estimates 24 , 25 .

Compared with the control group, combined dcEF + RL stimulation produced a highly significant increase in neurite length ( P = 2.1 × 10−29, η 2 = 0.54).

Moreover, the sample distributions in the X-axis and Y-axis show highly significant differences (Wilcoxon’s test P -value = 4.1 × 10 -29 ).

The association between the two classifications was found to be highly significant (χ 2 = 138.3, p = 6.4 × 10 −29 ).

In two-way (genotype and environment) ANOVA, the genotypic variations for the four index traits were highly significant ( P -value = 8.57e-29 ~ 3.62e-11) (Table S3 ), indicating the feasibility of conducting GWAS for the four index traits.

When we performed a gene-set enrichment analysis of these 1,341 genes using the Database for Annotation, Visualization and Integrated Discovery 20 , we found highly significant enrichment of ‘SP_PIR_KEYWORDS: alternative splicing' (Benjamini-corrected P =8.6 × 10 −29 ) and ‘UP_SEQ_FEATURE: splice variants' (Benjamini-corrected P =1.1 × 10 28 ), which denote genes with known splicing isoforms ( Supplementary Data 2 ).

The resulting Manhattan plot ( Figure 5B ) identified several highly significant metabolic hubs: 3.6.1 Stress-induced lipid amide accumulation The tentative lipid amide (m/z 338.33) was the most significant feature ( p < 10 -28 ), showing prominent accumulation in T3 and T4 samples as a marker for biotic stress. 3.6.2 Phenolic partitioning and correlation with lipid derivatives Quantitative analysis showed that Benzoic acid (GC_BA-TMS) levels were significantly higher in T2 compared to all other treatments.

Pathways showing highly significant results include the MAPK signalling pathway ( p -value = 1.29E-28), the FoxO signalling pathway ( p -value = 8.09E-19), the HIF-1 signalling pathway ( p -value = 9.65E-19), the PI3K-Akt signalling pathway ( p -value = 1.09E-18), and the insulin signalling pathway ( p -value = 2.87E-16).

8 , 9 The strongest and most highly significant associations have been reported with early-onset, persistent eczema 10 , 11 (odds ratio 5·6, 95% confidence interval 4·1–7·8, P = 1·3 × 10 −28 ) and asthma occurring in individuals with atopic eczema 12 – 14 (odds ratio 3·49, 95% confidence interval 2·00–6·08, P = 1·0 × 10 −5 ).