Novel Knowledge-Guided Generative Methods for Synthetic Transcriptomic Data

There is no consensus in the field of synthetic data on concise metrics for quality evaluations or benchmarks on large health datasets, such as historical epidemiological data. This study presents an evaluation of seven recent models from major machine learning families. The models were evaluated using four different datasets, each with a distinct scale. To ensure a fair comparison, we systematically tuned the hyperparameters of each model for each dataset. We propose a methodology for evaluating the fidelity of synthesized joint distributions, aligning metrics with visualization on a single plot. This method is applicable to any dataset and is complemented by a domain-specific analysis of the German Cancer Registries' epidemiological dataset. The analysis reveals the challenges models face in strictly adhering to the medical domain. We hope this approach will serve as a foundational framework for guiding the selection of synthesizers and remain accessible to all stakeholders involved in releasing synthetic datasets.

The growing demand for privacy-preserving data sharing has positioned synthetic data generation as a critical component of responsible AI workflows. Despite notable advances in generative modeling, existing solutions often lack integration of adaptive generation strategies, multi-metric evaluation, and accessible end-to-end generators within a unified web-based toolkit. In this work, we introduce TDGT (Tabular Data Generation Toolkit), a web-based toolkit for synthetic tabular data generation and fidelity assessment. TDGT introduces the Adaptive Bayesian Mixture Synthesizer (ABMS), a novel algorithm that autonomously determines the optimal number of mixture components through iterative cluster quality optimization, eliminating the need for manual hyperparameter configuration. Building upon ABMS, we further propose VAE-ABMS, a hybrid architecture that couples Variational Autoencoder-based latent space learning with adaptive Bayesian mixture synthesis, enabling high-fidelity generation of complex, nonlinear tabular distributions. For large-scale scenarios, TDGT provides a GPU-accelerated variant of ABMS leveraging CUDA-based k-means clustering and Gaussian mixture fitting. Synthetic data fidelity is assessed through eleven statistical fidelity metrics spanning distributional divergence, structural correlation, and sample-level similarity, complemented by privacy risk indicators including k-anonymity scoring and disclosure rate estimation. The web-based toolkit supports a real-time streaming interface with interactive Plotly-based visualizations. TDGT is assessed across datasets from healthcare, socioeconomic modeling, and cybersecurity domains, demonstrating consistent generation fidelity and statistical coherence across heterogeneous feature types and data scales.

Inferring gene regulatory networks (GRNs) from single-cell transcriptomic data is crucial for biological discovery, yet existing approaches suffer from a fundamental misalignment with real-world needs. Researchers typically seek a small set of high-confidence regulatory interactions for experimental validation, often involving previously unseen genes. However, current benchmarks rely on transductive splits with global classification metrics, while prevailing models struggle to generalize under inductive settings. To bridge this gap, we reformulate GRN inference as an inductive, ranking-centric graph completion problem and introduce \textbf{\benchmark}, a new benchmark that incorporates an inductive gene-holdout split together with knowledge graph completion metrics to better evaluate top-ranked predictions. Building on this, we propose \textbf{\method}, the first co-evolutionary discrete diffusion framework that jointly models biologically coherent discretized gene expression states and regulatory interactions for robust inductive generalization and improved top-ranked regulatory discovery. We further introduce TF-ALL Subgraph Sampling (TASS) for scalable training. Extensive experiments on {\benchmark} show that {\method} establishes new state-of-the-art performance, significantly outperforming existing methods in novel regulatory discovery, and ablation studies further verify the effectiveness of our design.