Artificial Intelligence-Enabled Radiogenomic Analysis for Non-invasive Molecular Subtyping of Adult Gliomas Using Standard Computed Tomography.


Ahmed Emam Z. A., Ada E., Pehlivanoğlu B., Çavuşoğlu B., Selver M. A., Akgüngör K.

48th ESNR Annual Meeting & 15th Asian-Oceanian Congress of Neuroradiology and Head and Neck Radiology & 34th Annual Meeting of the Turkish Society of Neuroradiology , İstanbul, Türkiye, 17 - 21 Eylül 2025, sa.9835261, ss.111, (Tam Metin Bildiri)

  • Yayın Türü: Bildiri / Tam Metin Bildiri
  • Doi Numarası: 10.10007/s00234-025-03726-7
  • Basıldığı Şehir: İstanbul
  • Basıldığı Ülke: Türkiye
  • Sayfa Sayıları: ss.111
  • Dokuz Eylül Üniversitesi Adresli: Evet

Özet

Artificial Intelligence-Enabled Radiogenomic Analysis for Non-invasive Molecular

Subtyping of Adult Gliomas Using Standard Computed Tomography

1 Zohal Alnour Ahmed Emam, 2 Emel Ada, 1 Berrin Çavuşoğlu, 3 Burçin Pehlivanoğlu, 4 M. Alper Selver, 5 Kadir

Akgüngör

1 Dokuz Eylul University, Institute of Health Sciences, Medical Physics Department, Izmir, Turkey

2 Dokuz Eylül University, Faculty of Medicine, Department of Radiology, Izmir, Turkey

3 Dokuz Eylul Hospital, Faculty of Medicine, Department of Pathology, Izmir, Turkey

4 Dokuz Eylul University, Electrical and Electronics Engineering Department and Izmir Health Technologies

Development and Accelerator (BioIzmir), İzmir, Turkey

5 Dokuz Eylul University, Department of Atomic and Molecular Physics, Izmir, Turkey

Abstract

Introduction: Molecular subtyping of gliomas is essential for treatment stratification according

to current WHO classification guidelines. Conventional molecular characterization requires

histopathological analysis following surgical resection or stereotactic biopsy, procedures

associated with perioperative morbidity and potential treatment delays. Radiogenomics, the

correlation of imaging phenotypes with genomic alterations, provides a non-invasive approach

for molecular profiling. This study investigates the application of machine learning algorithms to

standard computed tomography imaging for predicting key molecular markers in adult gliomas.

Methods: We retrospectively analyzed preoperative computed tomography scans from 197 adult

patients with histologically confirmed gliomas. Following quality control and data exclusion

criteria, the final cohort comprised 81 cases for alpha-thalassemia/mental retardation X-linked

(ATRX) analysis, 17 cases for epidermal growth factor receptor (EGFR) analysis, 71 cases for

p53 protein status analysis, and 183 cases for isocitrate dehydrogenase (IDH) analysis. Radiomic

feature extraction yielded 199 quantitative imaging biomarkers. Feature selection was performed

using hybrid Least Absolute Shrinkage and Selection Operator-Recursive Feature Elimination

(LASSO-RFE) and Gradient Boosting-Recursive Feature Elimination (GB-RFE) methods. Eight

machine learning classifiers were evaluated: Support Vector Machines (SVM), Random Forest

(RF), Multi-Layer Perceptron (MLP), Logistic Regression (LR), Extreme Gradient Boosting

(XGBoost), k-Nearest Neighbors (k-NN), TabNet, and deep neural networks (DNN) for

prediction of IDH, p53 protein status, EGFR, and ATRX mutations.


Results: TabNet performed with an area under the receiver operating characteristic curve (AUC)

of 0.900 and precision-recall area under curve (PR-AUC) of 0.983 for ATRX mutation

prediction; AUC of 0.917 and PR-AUC of 0.950 for EGFR amplification; and AUC of 0.955 and

PR-AUC of 0.917 for p53 protein status. Deep neural networks achieved AUC of 0.971 and PR-

AUC of 0.904 for IDH mutation status. Cross-validation analysis yielded coefficient of variation

(CV) values of 0.5-2% for ATRX (AUC and PR-AUC) and 0% for EGFR (both metrics).

Discussion & Conclusion: This study demonstrates that CT-based radiogenomic analysis can

successfully identify molecular markers in adult gliomas using machine learning approaches.

Through inclusive evaluation of eight algorithms, TabNet and deep neural networks achieved

optimal performance across four genetic targets. Cross-validation results confirmed model

stability and reproducibility. This work addresses the limited research utilizing CT for glioma

radiogenomics and establishes a validated methodology for non-invasive molecular profiling

using widely available imaging technology. The findings provide a foundation for expanding

radiogenomic applications beyond advanced MRI-based approaches.


Keywords: Radiogenomics; Artificial Intelligence; Glioma; Molecular Profiling; Computed

Tomography


Abstract tables:

Table 1 . Performance comparison of machine learning models for molecular marker prediction showing area

under the receiver operating characteristic curve (AUC) and precision-recall area under the curve (PR-AUC) for

each genetic target

Gene Model AUC PR

AUC

ATRX KNN 0.593 0.871

ATRX LR 0.579 0.903

ATRX MLP 0.586 0.903

ATRX RF 0.739 0.952

ATRX SVM 0.671 0.932

ATRX TabNet_model 0.900 0.983

ATRX XGBoost 0.525 0.880


ATRX nn_model 0.691 0.938

EGF

R

KNN 0.750 0.768

EGF

R

LR 0.583 0.793

EGF

R

MLP 0.583 0.793

EGF

R

RF 0.750 0.854

EGF

R

SVM 0.750 0.893

EGF

R

TabNet_model 0.917 0.950

EGF

R

XGBoost 0.458 0.554

EGF

R

nn_model 0.667 0.830

p53 KNN 0.511 0.463

p53 LR 0.546 0.487

p53 MLP 0.568 0.505

p53 RF 0.261 0.221

p53 SVM 0.591 0.392

p53 TabNet_model 0.955 0.917

p53 XGBoost 0.432 0.282

p53 nn_model 0.660 0.658

IDH KNN 0.929 0.640

IDH LR 0.967 0.886

IDH MLP 0.914 0.795

IDH RF 0.924 0.651

IDH SVM 0.900 0.789

IDH TabNet_model 0.890 0.754

IDH XGBoost 0.910 0.620

IDH nn_model 0.971 0.904


Table 2 . Five-fold cross-validation stability analysis coefficient of

variation (CV) of model performance metrics (AUC and PR-

AUC) across different radiomic feature sets for molecular

marker prediction

Gene Metric Mean Std

Dev

CV

(%)

ATRX AUC 0.966 0.020 2.10

ATRX PR

AUC

0.994 0.005 0.46

p53 AUC 0.960 0.029 2.97

p53 PR

AUC

0.906 0.074 8.15


EGF

R

AUC 1.000

0

0.000 0


EGF

R

PR

AUC

1.000

0

0.000 0

IDH AUC 0.823 0.135 16.40

IDH PR

AUC

0.679 0.124 18.33


Abstract images: 


Figure 1 . Receiver operating characteristic (ROC) curve for ATRX mutation prediction using the TabNet model.

The curve demonstrates the trade-off between sensitivity and specificity, with an area under the curve (AUC) of

0.900, indicating high discriminative performance for ATRX mutation status classification in adult gliomas based

on computed tomography radiomic features.


Figure 2 . Receiver operating characteristic (ROC) curve for EGFR amplification prediction using the TabNet

model. The analysis reveals robust diagnostic capability with an area under the curve (AUC) of 0.917,

establishing strong predictive accuracy for EGFR amplification detection in glioma cases through CT-based

radiomic feature analysis.


Figure 3 . Receiver operating characteristic (ROC) curve for p53 protein status prediction using the TabNet

model. The performance evaluation achieved an area under the curve (AUC) of 0.955, reflecting exceptional

classification capability for p53 protein status determination using computed tomography-derived quantitative

imaging parameters.


Figure 4 . Receiver operating characteristic (ROC) curve for IDH mutation prediction using the deep neural

network (DNN) model. The analysis achieved superior diagnostic performance with an area under the curve

(AUC) of 0.971, establishing the most accurate molecular classification among all genetic targets through CT-

based radiogenomic profiling.