1x10 15  (Cell Signaling Technology Inc)

Journal: Genome Biology

Article Title: Differences in 5'untranslated regions highlight the importance of translational regulation of dosage sensitive genes

doi: 10.1186/s13059-024-03248-0

Figure Lengend Snippet: Genes intolerant to LoF have longer and more complex 5’UTRs. A 5’UTRs increase in length with decreasing tolerance to LoF (Wilcoxon P <1x10 -15 ). The average 5’UTR length across all genes (202 bp) is shown by a dotted line. The y-axis was truncated at 1,500 bp (39 genes had 5’UTRs >1,500 bp). B The 5’UTRs of genes most intolerant to LoF have lower minimum free energy (MFE) scores, representing a higher propensity to fold and create structured mRNAs (Wilcoxon P <1x10 -15 ). The average MFE across all 5’UTRs is shown as a dotted line (-78.8). The y-axis was truncated at -1,000 (6 genes had MFE <-1000). C The 5’UTRs of genes most intolerant to LoF are more conserved. Average PhyloP scores are plotted for 5’UTRs, uORF start codons, uORF stop codons and start-stops. The dotted line denotes PhyloP=2. D Genes most intolerant to LoF are more likely to have uORFs (Chi-square P <1x10 -15 ) and start-stops (Chi-square P =8.5x10 -05 ) than genes most tolerant to LoF. The average numbers of each uAUG type across all 5’UTRs are shown by dotted lines. uORF: upstream open reading frame; oORF; overlapping open reading frame. E Genes most intolerant to LoF were significantly more likely to have multiple associated CAGE peaks when compared to genes most tolerant to LoF (CAGE peak >1, 91.9% vs 72.4%, Chi-square P <1x10 -15 ; CAGE peak ≥6, 44.6% vs 16.3%, Chi-square P <1x10 -15 ). F Whilst Ribo-seq uORFs in genes intolerant to LoF appear to more frequently have canonical start-codons, this difference is not statistically significant (Chi-square P =0.18). All statistical tests compare the lowest and highest two LOEUF deciles

Article Snippet: D Genes most intolerant to LoF are more likely to have uORFs (Chi-square P <1x10 -15 ) and start-stops (Chi-square P =8.5x10 -05 ) than genes most tolerant to LoF.

Techniques:

Journal: Genome Biology

Article Title: Differences in 5'untranslated regions highlight the importance of translational regulation of dosage sensitive genes

doi: 10.1186/s13059-024-03248-0

Figure Lengend Snippet: Comparison of 5’UTRs across disease genes sets. A The 5’UTRs of disease genes are significantly longer (Wilcoxon: DD dominant: P <1x10 -15 ; Onc: P =1.5x10 -05 ; TSG: P =2.9x10 -04 ; HS: P <1x10 -15 ; TS: P <1x10 -15 ) with the exception of DD recessive genes which are significantly shorter (Wilcoxon P =2.7x10 -08 ), when compared to the average across all genes. The median 5’UTR length for all genes (136 bp) is shown by the dotted black line. The x-axis was truncated at 2,000 bp (22 genes had 5’UTRs >2,000 bp). B Disease gene 5’UTRs are significantly more conserved (T-test: DD dominant: P <1x10 -15 ; Onc: P =9x10 -06 ; TSG: P =4.3x10 -08 ; HS: P <1x10 -15 ; TS: P <1x10 -15 ) except DD recessive genes which are significantly less conserved (T-test: P =4.9x10 -08 ), compared to all genes. The dotted black line is the median PhyloP score for all genes (0.28). C Disease genes significantly more often contain uORFs (Chi-square: DD dominant: 57.9%, P <1x10 -15 ; TSG=49.4%, P =6.5x10 -05 ; HS=45.7%, P <1x10 -15 ; TS=40.7%, P =1.4x10 -07 ), when compared to all 5’UTRs. Start-stops are only significantly enriched in HS genes ( P =3.1x10 -08 ). The dotted lines mark the percentage of all genes with each uAUG type

Article Snippet: D Genes most intolerant to LoF are more likely to have uORFs (Chi-square P <1x10 -15 ) and start-stops (Chi-square P =8.5x10 -05 ) than genes most tolerant to LoF.

Techniques: Comparison