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cdk-mediated-phosphorylation-of-idrs's Introduction

CDK-mediated phosphorylations of IDRs

J.M. Valverde & G. Dubra

This repository provides the source code and data for all the analyses performed in R for the publication “A Cyclin-dependent kinase-mediated phosphorylation switch of disordered protein condensation” (Valverde, Dubra et al., 2023). This current GitHub readme file was automatically generated, using R Studio, from an R markdown (README.Rmd) where all the code used in the paper is recompiled.

Main figures

Fig. 1

c

e

g

Fig. 2

b

c

d

f

Fig. 3

b

Xenopus

Human

c

## 
##  Wilcoxon signed rank test with continuity correction
## 
## data:  psites_diso by variable
## V = 206396, p-value < 2.2e-16
## alternative hypothesis: true location shift is not equal to 0
## 95 percent confidence interval:
##  -1.211715 -1.052488
## sample estimates:
## (pseudo)median 
##      -1.131956

## 
##  Wilcoxon signed rank test with continuity correction
## 
## data:  psites_diso by variable
## V = 22188, p-value < 2.2e-16
## alternative hypothesis: true location shift is not equal to 0
## 95 percent confidence interval:
##  -1.890087 -1.491565
## sample estimates:
## (pseudo)median 
##      -1.679388

## 
##  Wilcoxon signed rank test with continuity correction
## 
## data:  psites_diso by variable
## V = 1340, p-value = 1.019e-14
## alternative hypothesis: true location shift is not equal to 0
## 95 percent confidence interval:
##  -2.734868 -1.577823
## sample estimates:
## (pseudo)median 
##      -2.131005

d

e

Yeast

## 
##  Wilcoxon rank sum test with continuity correction
## 
## data:  Percentage of disorder by target
## W = 167690, p-value < 2.2e-16
## alternative hypothesis: true location shift is not equal to 0
## 95 percent confidence interval:
##  21.63845 31.47638
## sample estimates:
## difference in location 
##               26.64479

## 
##  Wilcoxon rank sum test with continuity correction
## 
## data:  Percentage of disorder by target
## W = 166252, p-value < 2.2e-16
## alternative hypothesis: true location shift is not equal to 0
## 95 percent confidence interval:
##  23.21311 34.28578
## sample estimates:
## difference in location 
##               28.64125

## 
##  Wilcoxon rank sum test with continuity correction
## 
## data:  Percentage of disorder by target
## W = 165710, p-value < 2.2e-16
## alternative hypothesis: true location shift is not equal to 0
## 95 percent confidence interval:
##  20.31818 30.31861
## sample estimates:
## difference in location 
##               25.25882

Human

## 
##  Wilcoxon rank sum test with continuity correction
## 
## data:  Percentage of disorder by target
## W = 7707108, p-value < 2.2e-16
## alternative hypothesis: true location shift is not equal to 0
## 95 percent confidence interval:
##  18.79420 22.82949
## sample estimates:
## difference in location 
##                20.8597

## 
##  Wilcoxon rank sum test with continuity correction
## 
## data:  Percentage of disorder by target
## W = 7269014, p-value < 2.2e-16
## alternative hypothesis: true location shift is not equal to 0
## 95 percent confidence interval:
##  16.62156 21.14240
## sample estimates:
## difference in location 
##               18.87039

## 
##  Wilcoxon rank sum test with continuity correction
## 
## data:  Percentage of disorder by target
## W = 7348738, p-value < 2.2e-16
## alternative hypothesis: true location shift is not equal to 0
## 95 percent confidence interval:
##  16.82185 21.06136
## sample estimates:
## difference in location 
##               18.95022

Xenopus

## 
##  Wilcoxon rank sum test with continuity correction
## 
## data:  Percentage of disorder by ANOVA
## W = 307032, p-value = 2.358e-13
## alternative hypothesis: true location shift is not equal to 0
## 95 percent confidence interval:
##  -10.849034  -6.152332
## sample estimates:
## difference in location 
##               -8.45844

## 
##  Wilcoxon rank sum test with continuity correction
## 
## data:  Percentage of disorder by ANOVA
## W = 278128, p-value = 4.832e-13
## alternative hypothesis: true location shift is not equal to 0
## 95 percent confidence interval:
##  -12.27983  -7.01995
## sample estimates:
## difference in location 
##              -9.613807

## 
##  Wilcoxon rank sum test with continuity correction
## 
## data:  Percentage of disorder by ANOVA
## W = 319366, p-value = 5.781e-10
## alternative hypothesis: true location shift is not equal to 0
## 95 percent confidence interval:
##  -10.862103  -5.641645
## sample estimates:
## difference in location 
##              -8.265359

f

##            subset     n   mean     sd   min     Q1 median     Q3     max
## 1 Phosphoproteome 15329 22.767 24.195 0.000  3.333 13.687 36.158 100.000
## 2             CDK   656 43.040 25.881 0.000 24.184 40.389 61.776 100.000
## 3            MAPK   408 36.539 25.173 0.000 15.237 31.296 53.273  98.487
## 4            AURK   412 44.438 24.141 0.291 27.811 40.845 60.857 100.000
## 5             PLK   459 39.847 25.215 0.000 18.771 38.403 57.566 100.000
## 6             NEK    43 28.806 22.094 2.448 10.339 25.741 43.054  85.624
## 7            DYRK    42 41.869 25.545 0.239 22.507 40.408 59.029  95.763
##   percZero
## 1    9.485
## 2    0.762
## 3    1.225
## 4    0.000
## 5    0.654
## 6    0.000
## 7    0.000

## 
##  Kruskal-Wallis rank sum test
## 
## data:  Percentage of disorder by subset
## Kruskal-Wallis chi-squared = 1064.1, df = 6, p-value < 2.2e-16

##            subset     n nvalid   mean     sd   min     Q1 median     Q3     max
## 1 Phosphoproteome 15329  15300 30.599 28.045 0.000  8.231 20.914 45.864 100.000
## 2             CDK   656    656 48.864 28.506 0.000 26.305 46.592 70.344 100.000
## 3            MAPK   408    408 41.036 28.074 0.000 15.497 35.394 61.269 100.000
## 4            AURK   412    412 50.031 27.638 0.000 28.291 44.873 72.685 100.000
## 5             PLK   459    459 46.872 29.169 0.346 21.257 45.455 69.699 100.000
## 6             NEK    43     43 33.073 26.195 0.000 10.570 30.476 50.330 100.000
## 7            DYRK    42     42 46.485 26.216 6.310 25.558 45.340 61.612  99.548
##   percZero
## 1    0.791
## 2    0.457
## 3    0.245
## 4    0.243
## 5    0.000
## 6    2.326
## 7    0.000

## 
##  Kruskal-Wallis rank sum test
## 
## data:  Percentage of disorder by subset
## Kruskal-Wallis chi-squared = 680.57, df = 6, p-value < 2.2e-16

##            subset     n nvalid   mean     sd    min     Q1 median     Q3
## 1 Phosphoproteome 15329  15309 43.241 25.440  1.980 21.942 37.717 62.359
## 2             CDK   656    656 61.190 23.712 10.583 43.233 61.230 80.563
## 3            MAPK   408    408 54.506 23.997  7.042 33.354 54.216 76.560
## 4            AURK   412    412 62.686 21.933 10.738 45.588 62.748 80.284
## 5             PLK   459    459 59.330 24.128 10.406 38.498 60.535 79.393
## 6             NEK    43     43 49.955 22.278 14.161 29.756 52.847 63.672
## 7            DYRK    42     42 59.229 24.553 19.616 40.189 59.548 74.960
##       max
## 1 100.000
## 2 100.000
## 3 100.000
## 4 100.000
## 5 100.000
## 6  95.455
## 7 100.000

## 
##  Kruskal-Wallis rank sum test
## 
## data:  Percentage of disorder by subset
## Kruskal-Wallis chi-squared = 751.44, df = 6, p-value < 2.2e-16

Fig. 4

a

b

Human

Xenopus

Fig. 6

b

c

Interphase

Interphase (high expression)

Mitosis

d

## 
##  Wilcoxon rank sum test with continuity correction
## 
## data:  thalf by group
## W = 18.5, p-value = 0.1232
## alternative hypothesis: true location shift is not equal to 0
## 95 percent confidence interval:
##  -13.370047   1.150055
## sample estimates:
## difference in location 
##              -4.977137

## 
##  Wilcoxon rank sum test with continuity correction
## 
## data:  thalf by group
## W = 0, p-value = 0.01421
## alternative hypothesis: true location shift is not equal to 0
## 95 percent confidence interval:
##  -23.110004  -6.819955
## sample estimates:
## difference in location 
##              -15.94311

## 
##  Wilcoxon rank sum test with continuity correction
## 
## data:  thalf by group
## W = 15, p-value = 0.008276
## alternative hypothesis: true location shift is not equal to 0
## 95 percent confidence interval:
##  -15.209962  -5.260037
## sample estimates:
## difference in location 
##              -11.23145

## 
##  Wilcoxon rank sum test with continuity correction
## 
## data:  percent by group
## W = 73, p-value = 0.005126
## alternative hypothesis: true location shift is not equal to 0
## 95 percent confidence interval:
##  11.17000 45.76001
## sample estimates:
## difference in location 
##               27.58075

## 
##  Wilcoxon rank sum test with continuity correction
## 
## data:  percent by group
## W = 24, p-value = 0.01421
## alternative hypothesis: true location shift is not equal to 0
## 95 percent confidence interval:
##  17.58995 51.27007
## sample estimates:
## difference in location 
##                30.0655

## 
##  Wilcoxon rank sum test with continuity correction
## 
## data:  percent by group
## W = 66, p-value = 0.5885
## alternative hypothesis: true location shift is not equal to 0
## 95 percent confidence interval:
##  -10.63997  17.64000
## sample estimates:
## difference in location 
##               2.790034

Fig. 7

c

## 
##  Kruskal-Wallis rank sum test
## 
## data:  Foci_Nucleus by Treat_collapsed
## Kruskal-Wallis chi-squared = 205.15, df = 5, p-value < 2.2e-16

## 
##  Pairwise comparisons using Wilcoxon rank sum test with continuity correction 
## 
## data:  Full_length_quant$Foci_Nucleus and Full_length_quant$Treat_collapsed 
## 
##         DMSO L- DMSO L+ OA L-   OA L+   PA L- 
## DMSO L+ 2.1e-14 -       -       -       -     
## OA L-   5.3e-11 0.0230  -       -       -     
## OA L+   8.6e-14 0.3149  0.1860  -       -     
## PA L-   7.0e-05 < 2e-16 < 2e-16 < 2e-16 -     
## PA L+   0.6424  2.0e-15 1.8e-11 2.1e-14 0.0011
## 
## P value adjustment method: BH

Supplemental information

Comparing predictors

This block compares the residues predicted as to be disordered across the entire proteomes of yeast and human using different disorders. A Venn diagram is generated to illustrate the overlap between different methods

Supp. Fig. 3

a

c

Supp. Fig. 4

c

d

Supp. Fig. 5

a

Yeast

Human

Xenopus

d

e

Calculate the porcentage of disorder of yeast and human CDK targets vs the rest of the phosphoproteome with all available predictors

Supp. Fig 6

Supp. Fig. 7

Deleted LR domain

## 
##  Kruskal-Wallis rank sum test
## 
## data:  Foci_Nucleus by Treat_collapsed
## Kruskal-Wallis chi-squared = 204.5, df = 5, p-value < 2.2e-16

## 
##  Pairwise comparisons using Wilcoxon rank sum test with continuity correction 
## 
## data:  dLR_quant$Foci_Nucleus and dLR_quant$Treat_collapsed 
## 
##         DMSO L- DMSO L+ OA L-   OA L+   PA L- 
## DMSO L+ < 2e-16 -       -       -       -     
## OA L-   2.3e-05 1.5e-10 -       -       -     
## OA L+   < 2e-16 0.8143  2.9e-09 -       -     
## PA L-   0.7618  < 2e-16 2.9e-05 < 2e-16 -     
## PA L+   0.3916  < 2e-16 0.0014  8.9e-16 0.5839
## 
## P value adjustment method: BH

Deleted N-terminus (Repeats + LR)

## 
##  Kruskal-Wallis rank sum test
## 
## data:  Foci_Nucleus by Treat_collapsed
## Kruskal-Wallis chi-squared = 147.74, df = 5, p-value < 2.2e-16

## 
##  Pairwise comparisons using Wilcoxon rank sum test with continuity correction 
## 
## data:  Repeats_LR_quant$Foci_Nucleus and Repeats_LR_quant$Treat_collapsed 
## 
##         DMSO L- DMSO L+ OA L-   OA L+   PA L-  
## DMSO L+ 8.0e-09 -       -       -       -      
## OA L-   0.032   4.4e-05 -       -       -      
## OA L+   1.4e-09 0.341   3.3e-06 -       -      
## PA L-   3.3e-06 < 2e-16 3.0e-11 < 2e-16 -      
## PA L+   0.776   1.4e-09 0.014   2.8e-10 7.7e-06
## 
## P value adjustment method: BH

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