Deep Learning Analysis of CBCT Images for Periodontal Disease: Phenotype-Level Concordance with Independent Transcriptomic and Microbiome Datasets

BACKGROUND: Periodontitis is a common inflammatory disease characterized by progressive loss of alveolar bone. Cone-beam computed tomography (CBCT) can visualize 3D periodontal bone defects, but its interpretation is time-consuming and examiner-dependent. Deep learning may support standardized CBCT assessment if performance and biological relevance are adequately characterized. METHODS: We used the publicly available MMDental dataset (403 CBCT volumes from 403 patients) to train a 3D ResNet-18 classifier for binary discrimination between periodontitis and healthy status based on volumetric CBCT scans. Volumes were split by subject into training (n = 282), validation (n = 60), and test (n = 61) sets. Model performance was evaluated using area under the receiver operating characteristic curve (AUROC), area under the precision-recall curve (AUPRC), and calibration metrics with 95% bootstrap confidence intervals. Grad-CAM saliency maps were used to visualize the anatomical regions driving predictions. To explore phenotype-level biological concordance, we analyzed an independent gingival transcriptomic cohort (GSE10334, n ≈ 220 arrays after quality control) and an independent oral microbiome cohort based on 16S rRNA amplicon sequencing, using unsupervised clustering, differential expression/abundance testing, and pathway-level summaries. RESULTS: On the held-out CBCT test set, the model achieved an AUROC of 0.729 (95% CI: 0.599-0.850) and an AUPRC of 0.551 (95% CI: 0.404-0.727). At a high-sensitivity operating point (sensitivity 0.95), specificity was 0.48, yielding an overall accuracy of 0.62. Grad-CAM maps consistently highlighted the alveolar crest and furcation regions in periodontitis cases, in line with expected patterns of bone loss. In the transcriptomic cohort, inferred periodontitis samples showed up-regulation of inflammatory and osteoclast-differentiation pathways and down-regulation of extracellular-matrix and mitochondrial programs. In the microbiome cohort, disease-associated samples displayed a dysbiotic shift with enrichment of classic periodontal pathogens and depletion of health-associated commensals. These omics patterns are consistent with an inflammatory-osteolytic phenotype that conceptually aligns with the CBCT-defined disease class. CONCLUSIONS: This study presents a proof-of-concept 3D deep learning model for CBCT-based periodontal disease classification that achieves moderate discriminative performance and anatomically plausible saliency patterns. Independent transcriptomic and microbiome analyses support phenotype-level biological concordance with the imaging-defined disease class, but do not constitute subject-level multimodal validation. Given the modest specificity, single-center imaging source, and inferred labels in the omics cohorts, our findings should be interpreted as exploratory and hypothesis-generating. Larger, multi-center CBCT datasets and prospectively collected paired imaging-omics cohorts are needed before clinical implementation can be considered.