Excerpts

The division of the San and Damara forager groups was in line with ADMIXTURE clustering, with highly significant correlations of admixture fractions between methods (Pearson correlation; R = 0.76 and 1.00, P -value = 1.21 × 10 −81 and 3.59 × 10 −13 ; Supplementary Fig. 5a, b ).

Remarkably, we observed a highly significant overlap (hypergeometric test, P = 2.44e-81) between the AS genes in smad1 -cKO (121/512) and smad1 -KD (121/660) PGCs (Fig. 7b ), such as ccdc187 (coiled-coil domain containing 187) that is involved in microtubule anchoring and located in the centrosome 51 , mak ( male germ cell associated kinase ) that encodes a serine/threonine protein kinase related to cell cycle regulation 52 , tinf2 ( TERF1-interacting nuclear factor 2 0) that encodes one subunit of shelterin complex involved in distinguishing between telomeres and DNA damage 53 , among others (Supplementary Fig. 7a ).

The overlaps with plasma were 47 (T1∩plasma) and 54 (M1∩plasma), both highly significant after Bonferroni correction (Fisher’s exact test p < 10−68 and p < 10−74; Supplementary Fig. 2a ), supporting the reliability of the plasma-derived ground truth.

Quantifying de novo junctions revealed a highly significant increase ( P Value = 10 −59 ) in splicing noise in the UC patients, as compared to the healthy donors (Fig. 5a ).

An example was NMU , for which DAESC-Mix reports highly significant dynamic ASE ( p = 1.93 × 10 − 59 ) and captures the haplotype combinations well ( p f i s h e r = 1.51 × 10 − 6 ).

The overall coupling index is equal to 11.2%, which is highly significant (log 10 ( p -value) = −57, Material and Methods), though individual coupling probabilities are quite low (3.4 ± 1.9% (s.d.)).

Using SEA with the ChEMBL database, SNAP was predicted to target human protein PHLPP1, with a maximum Tanimoto coefficient of 0.31 and a highly significant p -value ( p = 8.8 × 10 −55 ) 46 .

Furthermore, COWAS discovered a highly significant effect of the interaction between APOE and LDLR on AD risk ( P < 1e−50).

Consistent with our prior publications 14 , 15 , we found clear suppression of EWS::FLI1 induced targets that was highly significant at the TES with both LCE ( P = 1.1e-48) and HCE ( P = 1.5e-33)(Fig. 3b ).

In agreement with this, when restricting the analyses to Trans- CDS, ABO is still highly significant ( p = 1.18 × 10 −45 ), in contrast to OBP2B where the p -value drops dramatically ( p = 2.49 × 10 −13 ).

Subsequent memory effects in selective neurons Due to the preceding screening procedure, we found highly significant fractions of neurons responding selectively to one or more items in all recorded brain regions (all P < 10 –43 , binomial test, one-sided with n = total number of neurons per region, k = number of responsive neurons per region, P = 0.001, corresponding to the alpha level of our response criterion, refer to “item responses”, Fig. 2 , Fig.

There is also a mild but highly significant correlation between the total number of targets involved in a combination and percentile of cell lines in which it is synergistic (Spearman’s ρ = 0.21, P = 6.25 × 10 −42 ), (Fig. 6A ).

The difference in fit of the 13 models was highly significant ( p = 8 × 10 −40 , ANOVA), but there was no significant difference in the fits of the five top models, all of which incorporated a perseverative learning mechanism: Perseveration/Reward-learning model (PR model, ref. 36 ); differential forgetting Q -learning 33 ; ideal observer with perseveration (see Methods); ideal-observer Bayesian filters with perseveration for either a generic probabilistic reversal-learning task (see Methods), or a generic drifting reward probability task 37 .

Comparison of mean firing rates of responsive single neurons for the best location of each neuron in each training phase, after subtracting baseline activity, revealed a highly significant difference between stages (Fig. 3b ; 1-way ANOVA test, F 3,531 = 72.4, p = 2.87 × 10 −39 for the cue period, F 3,531 = 21.93, p = 2.12 × 10 −13 for the first delay period).

The results of the test were highly significant ( P = 3.41 × 10 −39 ; Fig. 4c, d ), proving that there is a strong relationship between the data-driven GGM and the known IgG glycosylation pathway.

These results were corroborated by the analysis of functional pathways using the ConsensusPathDB 25 (Methods); gene sets showed highly significant overlaps ( P <7.66 × 10 −39 –2.38 × 10 −05 ) with pathways involving OR and GPCR-related signalling and signal transduction, (extra-cellular matrix related) processes of inter-cellular communication, immunoregulatory processes and membrane-linked drug transport.

In addition, a highly significant number of these genes have a SMARCB1 ChIP-seq peak ( p -value = 5.43e −38 , Fig. 5b ), confirming that genes regulated by SWINGN share their regulation with SWI/SNF.

A highly significant S-PrediXcan signal ( p = 6.10e–38) was also obtained for this WDR19 intron cluster in testis, however the evidence for colocalization with the GWAS peak was low (PP.H4.abf = 0.39).

In contrast, subtle but highly significant differences were evident between the velocity profiles of correct and incorrect saccades at long rPTs (mean peak velocity, correct versus incorrect: monkey R, p = 10 −37 ; monkey T, p = 10 −50 ; monkey G, p = 10 −27 ; Wilcoxon rank-sum test; Fig. 2c ).

We found a highly significant replication (mean R 2 for expression = 0.071; p = 1.3 × 10 −36 ; mean R 2 for splicing = 0.047; p = 2.1 × 10 −29 ), with 50.2% genes and splicing having R 2 > 0.01 (Supplementary Figure 9 ).

Although this genetic risk score shows a highly significant association in Caucasian ( P =3.94 × 10 −36 ), there is no evidence of association in the Chinese population ( P =0.21; Fig. 5 ).

Of the top 100 proteins highest in the s11 subtype, 58 were among the top 10% brain tissue-specific genes, a highly significant overlap ( p < 1E−35, one-sided Fisher’s exact test).

The enrichment of upregulated SFs in the upregulated genes is statistically highly significant ( P < 3.517 × 10 −34 , hypergeometric test).

A second, highly significant set of associated variants in 1q32.2 was defined by the lead SNP rs570516915 ( P = 5.25 × 10 –34 , OR = 8.65, Fig. 2b ).

This represented a highly significant difference (two-way analysis of variance (ANOVA) with factors young/adult stage, and individual monkey; F 1,304 =189.7 for main effect of stage, P =7.2 × 10 −34 ).