Identification of five important genes to predict glioblastoma subtypes

Glioblastoma (GBM), the most common and aggressive primary brain tumour in adults, has been classified into three subtypes: classical, mesenchymal, and proneural. While the original classification relied on an 840 gene-set, further clarification on true GBM subtypes uses a 150-gene signature to accurately classify GBM into the three subtypes. We hypothesized whether a machine learning approach could be used to identify a smaller gene-set to accurately predict GBM subtype.

Using a supervised machine learning approach, extreme gradient boosting (XGBoost), we developed a classifier to predict the three subtypes of glioblastoma (GBM): classical, mesenchymal, and proneural. We tested the classifier on in-house GBM tissue, cell lines, and xenograft samples to predict their subtype.

We identified the five most important genes for characterizing the three subtypes based on genes that often exhibited high Importance Scores in our XGBoost analyses. On average, this approach achieved 80.12% accuracy in predicting these three subtypes of GBM. Furthermore, we applied our five-gene classifier to successfully predict the subtype of GBM samples at our centre.

Our 5-gene set classifier is the smallest classifier to date that can predict GBM subtypes with high accuracy, which could facilitate the future development of a five-gene subtype diagnostic biomarker for routine assays in GBM samples.