Cite as: Assessment of branch point prediction tools to predict physiological branch points and their alteration by variants. Raphaël LEMAN, Hélène Tubeuf, Sabine Raad, Isabelle Tournier, Céline Derambure, Raphaël Lanos, Pascaline Gaildrat, Gaia Castelain, Julie Abdat, Audrey Kilian, Stéphanie Baert-Desurmont, Angelina Legros, Nicolas Goardon, Céline Quesnelle, Agathe Ricou, Laurent Castera, Dominique Vaur, Gérald Le Gac, Chandran Ka, Yann Fichou, Françoise Bonnet-Dorion, Nicolas Sevenet, Marine Guillaud-Bataille, Nadia Boutry-Kryza, Inès Schultz, Virginie Caux-Moncoutier, Maria Rossing, Logan C. Walker, Amanda B. Spurdle, Claude Houdayer, Alexandra Martins, Sophie Krieger
This repository contains the data and scripts used for this study. Three sets of data were used: the Ensembl data, the RNAseq data and variant data. The scripts used to compare bioinformatics tools (HSF, SVM-BPfinder, BPP, Branchpointer, LaBranchoR and RNABPS) are in R language.
To run these scripts, the following dependencies are needed:
- R (v3.0 or later)
sudo apt-get update
sudo apt-get install r-base r-base-dev- package 'ROCR'
install.packages('ROCR')- package 'gplots'
install.packages('gplots')- package 'ggplot2'
install.packages('ggplot2')- package 'VennDiagram'
install.packages('VennDiagram')Download the repository and the Ensembl data
git clone https://github.com/raphaelleman/BenchmarkBPprediction
cd ./BenchmarkBPpredictionDownload Branch point data from Ensembl dataset. Then put it in the 'data' folder.
#Usage Example
Rscript ./scripts/studyRNAseqBP.rThe script studyEnsemblBPscore.r is deicated to the Ensembl data and permits to perform:
- ROC analysis
- VENN diagram
The script studyRNAseqBP.r is deicated to the RNAseq data and permits to perform:
- ROC analysis
- VENN diagram
- Boxplot expression according to presence or not of Branch point
- Correlation expression and branch point score
The script studyVariantBPscore.r is deicated to the variant data and permits to perform:
- Histogram of variant repartition
- ROC analysis
- Histogram of relatif repartition
- Score combination by regresion logistic
Hereafter, the scheme of each data set use in this study.
The set of natural 3'ss and control AG
| Column names | Description |
|---|---|
| Chr | Chromosone of 3'ss |
| strand | Strand of transcript |
| sstype | "Acc", acceptor splice site |
| pos | Position of 3'ss (hg19) |
| UsedSite | 1- alternative 3'ss, 0- control AG |
| MES | MES score |
| SSF | SSF-like score |
| ESR | ESRseq score |
| Branch_class | Score above optimal threshold (Branchpointer) |
| Branch_pos | Position of predicted BP by Branchpointer |
| Branch_score | Score of predicted BP by Branchpointer |
| zscBPP | Score of predicted BP by BPP |
| zscSVM | Score of predicted BP by SVM-BPfinder |
| scoreLB | Score of predicted BP by LaBranchoR |
| scoreRNABPS | Score of predicted BP by RNABPS |
The set of alternative 3'ss indentified from RNAseq data
| Column names | Description |
|---|---|
| chr | Chromosone of 3'ss |
| Start_hg19 | Start of the junction (End if strand -) |
| Pos_hg19 | Position of 3'ss (hg19) |
| Strand | Strand of transcript |
| Transcript | Transcript name (RefSeq) |
| Gene | Gene symbol |
| UsedSite | 1- alternative 3'ss, 0- control AG |
| Expression_Average_(%) | Average expression in % ("." for control AG) |
| Expression_Average_(read) | Average expression in read count ("." for control AG) |
| nbSamp | Nb samples supporting the alternative 3'ss ("." for control AG) |
| MES | MES score |
| SSF | SSF-like score |
| bp_pos | Position of predicted BP by BPP |
| bp_zsc | Score of predicted BP by BPP |
| BPP_class | Score above optimal threshold (BPP) |
| ss_dist | Position of predicted BP by SVM-BPfinder |
| svm_scr | Score of predicted BP by SVM-BPfinder |
| SVM_class | Score above optimal threshold (SVM-BPfinder) |
| branchpoint_dist | Position of predicted BP by Branchpointer |
| branchpoint_prob | Score of predicted BP by Branchpointer |
| branchpoint_class | Score above optimal threshold (Branchpointer) |
| LB_pos | Position of predicted BP by LaBranchoR |
| LB_score | Score of predicted BP by LaBranchoR |
| LB_class | Score above optimal threshold (LaBranchoR) |
| RNABPS_pos | Position of predicted BP by RNABPS |
| RNABPS_score | Score of predicted BP by RNABPS |
| RNABPS_class | Score above optimal threshold (RNABPS) |
| Cum_class | Overlapping of predictions |
The collection of variant with their in vitro RNA studies.
| Column names | Description |
|---|---|
| ID | Name of variant |
| chr | Chromosome |
| strand | Strand of transcript (+: forward, -: reverse) |
| gene | Gene Name |
| transcript | Transcript ID (RefSeq) |
| intron | Intron number |
| cNomen | Transcriptomic coordinate |
| gNomen | Genomic coordinate (hg19) |
| distSS | Distance between variant and Acceptor site |
| varType | Type of mutation |
| nb_analyse | Number of study for the variant |
| Assay.Method | Materiel and Method used |
| Authora | The contributor |
| published | If the RNA studies were published or not |
| Result | Overall impact of variant on splicing |
| class_effect | Class of splicing alteration (0: no impact, 1: splicing alteration) |
| MES_wt | MES score of acceptor splice site (wildType) |
| MES_mut | MES score of acceptor splice site (mutated) |
| delta_MES | Delta MES score |
| SSF_wt | SSF-like score of acceptor splice site (wildType) |
| SSF_mut | SSF-like score of acceptor splice site (mutated) |
| delta_SSF | Delta SSF-like score |
| to_3prime | Distance between variant and Acceptor site |
| BP_num_REF | Number of branch point found by branchpointer (wildType) |
| BP_num_ALT | Number of branch point found by branchpointer (mutated) |
| deleted_n | Number of deleted branch points (branchpointer) |
| created_n | Number of created branch points (branchpointer) |
| max_prob_REF | Branchpointer score, maximal value (wildType) |
| max_prob_ALT | Branchpointer score, maximal value (mutated) |
| max_U2_REF | U2 score (acceptor site, wildType) |
| max_U2_ALT | U2 score (acceptor site, mutated) |
| PosPB_Branch | Position of branch point with maximal score |
| ProbPBarea_Branch | Interval of 4-mer motif of branch point |
| MutInPBarea_Branch | If variant was in the 4-mer of branch point |
| Delta_prob | Delta Branchpointer score |
| bps_WT | Sequence of wildType Branch point with maximal score |
| bps_MUT | Sequence of mutated Branch point with maximal score |
| bp_pos_WT | Relative position of branch point to the acceptor site (wildType) |
| bp_pos_MUT | Relative position of branch point to the acceptor site (mutated) |
| zsc_WT | BPP score (wildType) |
| zsc_MUT | BPP score (mutated) |
| PosPB_BPP | Position of branch point with maximal score |
| ProbPBarea_BPP | Interval of 4-mer motif of branch point |
| MutInPBarea_BPP | If variant was in the 4-mer of branch point |
| Delta_BPP | Delta score of BPP |
| ss_dist_WT | Relative position of branch point to the acceptor site (wildType) |
| ss_dist_MUT | Relative position of branch point to the acceptor site (mutated) |
| bp_seq_WT | Sequence of wildType Branch point with maximal score |
| bp_seq_MUT | Sequence of mutated Branch point with maximal score |
| svm_scr_WT | SVM-BPfinder score (wildType) |
| svm_scr_MUT | SVM-BPfinder score (mutated) |
| PosPB_SVM | Position of branch point with maximal score |
| ProbPBarea_SVM | Interval of 4-mer motif of branch point |
| MutInPBarea_SVM | If variant was in the 4-mer of branch point |
| Delta_SVM | Delta score of SVM-BPfinder |
| score_wt | HSF score (wildType) |
| score_mut | HSF score (mutated) |
| delta_HSF | Delta score of HSF |
| interpret | Overall prediction of HSF |
| LB_pos_WT | Relative position of branch point to the acceptor site (wildType) |
| LB_pos_MUT | Relative position of branch point to the acceptor site (mutated) |
| LB_score_WT | LaBranchoR score (wildType) |
| LB_score_MUT | LaBranchoR score (mutated) |
| PosPB_LB | Position of branch point with maximal score |
| ProbPBarea_LB | Interval of 4-mer motif of branch point |
| MutInPBarea_LB | If variant was in the 4-mer of branch point |
| Delta_LB | Delta score of LaBranchor |
| RBPS_posA_WT | Relative position of branch point to the acceptor site (wildType) |
| RBPS_posA_MUT | Relative position of branch point to the acceptor site (mutated) |
| RBPS_score_WT | RNABPS score (wildType) |
| RBPS_score_MUT | RNABPS score (mutated) |
| PosPB_RBPS | Position of branch point with maximal score |
| ProbPBarea_RBPS | Interval of 4-mer motif of branch point |
| MutInPBarea_RBPS | If variant was in the 4-mer of branch point |
| Delta_RBPS | Delta score of RNABPS |