BenchmarkBPprediction

---

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.

Installation and Usage

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 ./BenchmarkBPprediction

Download Branch point data from Ensembl dataset. Then put it in the 'data' folder.

#Usage Example
Rscript ./scripts/studyRNAseqBP.r

SCRIPTS

The 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

DATA

Hereafter, the scheme of each data set use in this study.

Ensembl data

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

RNAseq data

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

Variant data

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