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A transcriptome-based classifier to determine molecular subtypes in medulloblastoma.
- Source :
-
PLoS computational biology [PLoS Comput Biol] 2020 Oct 29; Vol. 16 (10), pp. e1008263. Date of Electronic Publication: 2020 Oct 29 (Print Publication: 2020). - Publication Year :
- 2020
-
Abstract
- Medulloblastoma is a highly heterogeneous pediatric brain tumor with five molecular subtypes, Sonic Hedgehog TP53-mutant, Sonic Hedgehog TP53-wildtype, WNT, Group 3, and Group 4, defined by the World Health Organization. The current mechanism for classification into these molecular subtypes is through the use of immunostaining, methylation, and/or genetics. We surveyed the literature and identified a number of RNA-Seq and microarray datasets in order to develop, train, test, and validate a robust classifier to identify medulloblastoma molecular subtypes through the use of transcriptomic profiling data. We have developed a GPL-3 licensed R package and a Shiny Application to enable users to quickly and robustly classify medulloblastoma samples using transcriptomic data. The classifier utilizes a large composite microarray dataset (15 individual datasets), an individual microarray study, and an RNA-Seq dataset, using gene ratios instead of gene expression measures as features for the model. Discriminating features were identified using the limma R package and samples were classified using an unweighted mean of normalized scores. We utilized two training datasets and applied the classifier in 15 separate datasets. We observed a minimum accuracy of 85.71% in the smallest dataset and a maximum of 100% accuracy in four datasets with an overall median accuracy of 97.8% across the 15 datasets, with the majority of misclassification occurring between the heterogeneous Group 3 and Group 4 subtypes. We anticipate this medulloblastoma transcriptomic subtype classifier will be broadly applicable to the cancer research and clinical communities.<br />Competing Interests: The authors have declared that no competing interests exist.
- Subjects :
- Databases, Genetic
Genomics
Humans
Oligonucleotide Array Sequence Analysis
Cerebellar Neoplasms classification
Cerebellar Neoplasms genetics
Cerebellar Neoplasms metabolism
Gene Expression Profiling methods
Medulloblastoma classification
Medulloblastoma genetics
Medulloblastoma metabolism
Software
Transcriptome genetics
Subjects
Details
- Language :
- English
- ISSN :
- 1553-7358
- Volume :
- 16
- Issue :
- 10
- Database :
- MEDLINE
- Journal :
- PLoS computational biology
- Publication Type :
- Academic Journal
- Accession number :
- 33119584
- Full Text :
- https://doi.org/10.1371/journal.pcbi.1008263