OutSplice: A Novel Tool for the Identification of Tumor-Specific Alternative Splicing Events
Abstract
:1. Introduction
2. Materials and Methods
2.1. Data Preparation
2.2. Computational Resources
2.3. Genome Index Building and Alignment
2.4. Algorithm Data Formatting Pipelines
2.4.1. OutSplice Pipeline
2.4.2. edgeR Pipeline
2.4.3. LeafCutter/LeafCutterMD Pipeline
2.4.4. Psichomics Pipeline
2.4.5. rMATs Pipeline
2.4.6. Whippet Pipeline
2.4.7. FRASER Pipeline
2.4.8. Simulated Data Creation
3. Results and Discussion
3.1. OutSplice
3.2. edgeR
3.3. LeafCutter
3.4. Psichomics
3.5. rMATS
3.6. Whippet
3.7. Gene Overlap and Algorithm Comparisons
3.8. Outlier Analysis and Comparison
4. Conclusions
Supplementary Materials
Author Contributions
Funding
Institutional Review Board Statement
Informed Consent Statement
Data Availability Statement
Conflicts of Interest
References
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Gene with Significant Splicing Event(s) | Description | Event Types Found | edgeR | LeafCutter | OutSplice | Psichomics | rMATS | Whippet |
---|---|---|---|---|---|---|---|---|
ECM1 | Extracellular Matrix Protein 1 | Skipping and Alternative 5′ Splice Sites | X | X | X | X | X | |
COL6A3 | Collagen type VI alpha-3 chain | Skipping and Mutually Exclusive Exons | X | X | X | X | X | |
KIAA1217 | Embryonic skeletal system development | Skipping, Alternative First Exon, Retained Intron, and Mutually Exclusive Exons | X | X | X | X | X | |
HDAC9 | Histone deacetylase 9 | Skipping, Alternative First Exon, Tandam Start Site, and Mutually Exclusive Exons | X | X | X | X | X | |
MBNL1 | Muscleblind-like splicing regulator 1 | Skipping and Mutually Exclusive Exons | X | X | X | X | X | |
VPS39 | VPS39 subunit of the HOPS complex | Skipping and Tandam Start Site | X | X | X | X | X | |
PLEKHG1 | Pleckstrin homology and RhoGEF domain containing G1 | Skipping, Insertion, Tandam Start Site, and Mutually Exclusive Exons | X | X | X | X | X | X |
ITGB4 | Integrin subunit beta 4 | Skipping | X | X | X | X | X | X |
PTPN6 | Protein tyrosine phosphatase non-receptor type 6 | Skipping, Alternative Acceptor, Alternative First Exon, Alternative 3′ Start Site, Mutually Exclusive Exons, and Retained Introns | X | X | X | X | X | |
MTMR1 | Myotubularin-related protein 1 | Skipping and Mutually Exclusive Exons | X | X | X | X | X | |
PARD3 | Par-3 family cell polarity regulator | Skipping, Alternative 5′ Splice Site, Alternative First Exon, and Mutually Exclusive Exons | X | X | X | X | X | |
NUMA1 | Nuclear mitotic apparatus protein 1 | Alternative First Exon, Tandem Transcription Start Site, Retained Intron, and Mutually Exclusive Exons | X | X | X | X | X | |
RABGAP1L | RAB GTPase-activating protein 1 | Skipping and Insertion | X | X | X | X | X | |
MDM2 | Proto-oncogene | Skipping, Alternative First Exon, and Mutually Exclusive Exons | X | X | X | X | X | |
MCM7 | Minichromosome maintenance complex component 7 | Skipping, Alternative First Exon, and Retained Intron | X | X | X | X | X | |
MEI1 | Meiotic double-stranded break formation protein 1 | Skipping, Insertion, and Deletion Events | X | X | X | X | X | |
FCGR2B | FC gamma receptor IIb | Skipping and Retained Intron | X | X | X | X | X |
Identified Genes | Identified + Significant Genes | |||||||||
---|---|---|---|---|---|---|---|---|---|---|
True Positive | Total Identified | Sensitivity | Specificity | FDR | True Positive | Total Identified + Significant | Sensitivity | Specificity | FDR | |
edgeR | 200 | 1014 | 1 | 0.03 | 0.8 | 192 | 265 | 0.96 | 0.91 | 0.28 |
LeafCutter | 185 | 213 | 0.93 | 0.97 | 0.13 | 181 | 194 | 0.91 | 0.98 | 0.07 |
OutSplice | 91 | 366 | 0.46 | 0.67 | 0.75 | 78 | 336 | 0.39 | 0.69 | 0.77 |
psichomics | 108 | 123 | 0.54 | 0.98 | 0.12 | 102 | 115 | 0.51 | 0.98 | 0.11 |
rMATS | 149 | 392 | 0.75 | 0.70 | 0.62 | 115 | 120 | 0.58 | 0.99 | 0.04 |
Whippet | 200 | 972 | 1 | 0.07 | 0.79 | 77 | 79 | 0.39 | 1 | 0.03 |
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Bendik, J.; Kalavacherla, S.; Webster, N.; Califano, J.; Fertig, E.J.; Ochs, M.F.; Carter, H.; Guo, T. OutSplice: A Novel Tool for the Identification of Tumor-Specific Alternative Splicing Events. BioMedInformatics 2023, 3, 853-868. https://doi.org/10.3390/biomedinformatics3040053
Bendik J, Kalavacherla S, Webster N, Califano J, Fertig EJ, Ochs MF, Carter H, Guo T. OutSplice: A Novel Tool for the Identification of Tumor-Specific Alternative Splicing Events. BioMedInformatics. 2023; 3(4):853-868. https://doi.org/10.3390/biomedinformatics3040053
Chicago/Turabian StyleBendik, Joseph, Sandhya Kalavacherla, Nicholas Webster, Joseph Califano, Elana J. Fertig, Michael F. Ochs, Hannah Carter, and Theresa Guo. 2023. "OutSplice: A Novel Tool for the Identification of Tumor-Specific Alternative Splicing Events" BioMedInformatics 3, no. 4: 853-868. https://doi.org/10.3390/biomedinformatics3040053