Machine Learning
A Physics-Regulated Neural Framework for Learning 3D Grain Growth Dynamics
Zhihui Tian, Kang Yang, Michael Tonks et al. (+2 more)
Grain growth is governed by the reduction in grain boundary energy and exhibits well-established statistical scaling laws. Developing data-driven surrogates that preserve these physical invariants while remaining computationally scalable remains challenging, especially in 3D. We present 3D-PRIMME (Physics-Regulated Interpretable Machine Learning for Microstructure
Evolution) for learning three-dimensional grain growth dynamics. The model is trained using only two consecutive time steps yet accurately reproduces the linear coarsening law and preserves topological statistics over extended time scales. Despite being trained on a $100^3$ grid points with 512 grains, the learned
evolution operator is applied to domains up to $1024^3$ grid points with 550000 grains without retraining, maintaining consistent kinetics and grain
topology across orders-of-magnitude increases in system size. These results demonstrate that 3D-PRIMME learns a scale-independent and temporally stable local
evolution rule, enabling efficient and robust large-scale surrogate prediction of 3D microstructure
evolution.
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All authors Zhihui Tian, Kang Yang, Michael Tonks, Amanda R. Krause, Joel B. Harley
Machine Learning · Cross-listed from cs.CV
GlaKG: A Biomarker-Centric Fundus Knowledge Graph for Explainable Glaucoma Diagnosis and Risk Assessment
Cheng Huang, Jia Zhang, Yi Jiang et al. (+7 more)
Glaucoma is a leading cause of irreversible blindness worldwide, yet most automated diagnosis systems rely on opaque deep-learning models that offer little clinical interpretability. We present GlaKG, a biomarker-centric fundus knowledge graph that integrates structural biomarkers, clinically grounded rules, and image features to produce traceable
reasoning for glaucoma diagnosis and risk stratification. GlaKG encodes six entity types (Fundus Image, Optic Disc, Neural Rim, Pathology, Diagnosis, Risk Level), eight relation types, and 11 clinically validated rules into a unified graph, so that every prediction is accompanied by an explicit
reasoning chain linking biomarker evidence to activated clinical rules. To keep knowledge-based
reasoning strictly separate from label information, we adopt a post-processing fusion framework that combines ResNet50 image
embeddings with a normalized KG
reasoning-chain score via a tunable weight alpha, with all fitting confined to the training split. On a publicly available, AI-annotated fundus
dataset, GlaKG reaches F1 = 0.9953 for binary glaucoma classification and 0.930 accuracy with 0.922 weighted F1 for four-class risk stratification; we report openly that the
dataset's biomarker annotations are highly label-correlated, and therefore frame these figures as an upper bound attainable with clean structured biomarkers rather than as leakage-free image-only performance. Feature-importance analysis shows KG-derived and biomarker features contributing near-equally (51.1% vs. 48.9%), and the
reasoning chain flags borderline cases by exposing low chain scores rather than failing silently. GlaKG's central contribution is therefore a clinically auditable
reasoning framework that complements raw predictive performance by explicitly exposing the biomarker evidence and rule activations behind each decision.
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All authors Cheng Huang, Jia Zhang, Yi Jiang, Yang Liu, Karanjit Kooner, Yadi Liu, Tsengdar Lee, Yang Xie, Wenqi Shi, Guanghua Xiao
Machine Learning · Cross-listed from stat.ML
Decomposition for Bayesian Networks: Local and Parallel Inference
Pei Heng, Xinyi Hu and Yi Sun
Probabilistic inference in high-dimensional
Bayesian networks is difficult because exact manipulation of the joint distribution scales exponentially with network size. We propose a decomposition framework based on directed convex subgraphs and introduce a minimal d-decomposition tree. Together, they provide a principled alternative to classical junction-tree constructions. The proposed framework represents the joint distribution by lower-dimensional sub-models that can be learned and stored separately. This decomposition reduces computational cost and naturally enables parallel computation. Based on a minimal d-decomposition tree, we further develop two parallel
algorithms for parameter estimation and probabilistic inference. Experiments show that the proposed method substantially improves computational efficiency over junction-tree methods while maintaining inference accuracy, especially for low-dimensional queries.
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Machine Learning
Machine Learning for Depression Screening and Intervention: an Original Circadian Rhythm Score-based Methodology
Bin Wang, Shuo Lian, Yuanyuan Hou et al. (+5 more)
Depression screening from large-scale behavioral data is challenged by fragmented circadian indicators, limited interpretability, and the lack of intervention-oriented analysis. Existing approaches typically analyze sleep, activity, and social behaviors in isolation, failing to capture their joint circadian structure. To address this limitation, we first propose the Circadian Rhythm Score (CRS), a composite index that compresses multi-domain daily behaviors into a unified representation of circadian rhythm. CRS is constructed to maximize discriminative power for depression screening while preserving behavioral semantics through non-negativity constraints. Empirical results demonstrate near-lossless compression, where a single CRS retains almost the full predictive capability compared with multiple raw behavioral indicators. Building upon CRS, we develop an interpretable depression screening framework based on gradient-boosted trees and SHAP analysis, revealing nonlinear and saturation-like associations between circadian rhythm and depression risk. Beyond risk prediction, we further integrate interaction modeling and counterfactual regression to estimate heterogeneous and dose-dependent behavioral effects, enabling intervention-oriented
reasoning under different circadian contexts. Experiments on the China Health and Retirement Longitudinal Study (CHARLS, n=15,233), demonstrate robust screening performance (ROC-AUC=0.825) and identify actionable behavioral thresholds, including a minimum effective exercise dose of approximately 300 MET-min/week and an optimal restorative nap duration of approximately 65 minutes for sleep-deprived individuals. By bridging supervised representation learning and interpretable modeling, this work provides a scalable framework for depression screening and intervention-aware healthcare data mining.
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All authors Bin Wang, Shuo Lian, Yuanyuan Hou, Dexian Wang, Peilan He, Feng Hong, Yanwei Yu, Tianrui Li
Machine Learning · Cross-listed from stat.ML
Integrating Neural Encoders in Bayesian Generalized Linear Mixed Models for Multimodal Data
Yuankang Zhao, Youngsoo Baek, Felipe A. Medeiros et al. (+2 more)
Scalable
Bayesian inference for generalized linear mixed models (GLMMs) provides uncertainty-aware analysis of correlated longitudinal data, but existing scalable approaches largely assume low-dimensional tabular predictors and do not directly accommodate high-dimensional modalities such as images and text. We address this limitation by learning one or more modality-specific neural encoders jointly with a GLMM objective, then performing variance-corrected stochasticgradient MCMC for the GLMM parameters conditional on the learned representation. This conditional-Bayes design combines supervised representation learning with posterior uncertainty quantification for population-level effects, subjectspecific heterogeneity, and modality-level random slopes. The resulting model preserves interpretable fixed and random effects for structured
covariates and learned modalities while scaling gracefully to large longitudinal
datasets. In simulation studies, our method recovers posterior means and variance estimates from full-data MCMC
benchmarks after covariance correction. We further evaluate uncertainty through parameter-level interval coverage in simulations and predictive calibration on held-out data. Applications to glaucoma progression and adolescent mental health demonstrate that the framework allows nuanced assessment of the relative importance of each modality on both individual and population levels without sacrificing predictive performance.
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All authors Yuankang Zhao, Youngsoo Baek, Felipe A. Medeiros, Samuel Berchuck, Matthew M. Engelhard
Machine Learning · Cross-listed from cs.CL
Retroactive Chain-of-Thought (RetroCoT): Forensic Reconstruction Prompts as a Safety Diagnostic Across Model Generations
Samira Hajizadeh
Safety
alignment in large
language models is typically evaluated against direct, imperative harmful requests. We show that this
alignment is highly conditioned on pragmatic register: models that refuse a direct request frequently comply when the same underlying objective is expressed through a different communicative stance. This suggests that current
alignment policies are not invariant to semantic equivalence, but remain sensitive to how a request is pragmatically framed. We introduce Retroactive Chain-of-Thought (RetroCoT), a single-turn attack that reframes harmful requests as forensic reconstruction tasks. Rather than requesting harmful instructions directly, RetroCoT presupposes that the harmful outcome has already occurred and asks the model, acting as a forensic analyst, to reconstruct in reverse the causal chain that produced it. On AdvBench (n=50), RetroCoT achieves attach success rate of 58% on gpt-4o and 52% on gpt-4o-mini, compared with direct-request baselines of 0% and 4%, respectively. We further identify a pronounced generation gap: GPT-5-family models refuse RetroCoT entirely, explicitly identifying the reconstruction premise in their refusal rationales, consistent with explicit coverage of this reconstruction register. However, this robustness does not generalize across pragmatic forms. A single
adversarial feedback turn presenting an existing forensic reconstruction response alongside evaluator critique raises ASR from 0% to 48% on GPT-5.4-mini and from 58% to 94% on GPT-4o; a control condition omitting the fabricated low score achieves 85% on GPT-5.4-mini, indicating that the operative element is pragmatic continuation within the established forensic frame rather than score manipulation. These results suggest that frontier-model
alignment remains conditioned on pragmatic framing rather than semantic intent, and that new pragmatic registers can continue to expose a...
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Machine Learning
Reliability and Identifiability in Persona-Trained Monte Carlo: Variance Decomposition, Stability Bounds, and the Identifiability of Heterogeneous News Reaction
Salavat Ishbulatov
Persona-Trained Monte Carlo (PTMC) estimates distributions of
market-outcome functionals by repeatedly simulating limit-order-book interaction among $K$ neural policy bots whose behavioral personas are drawn from a learned heterogeneity distribution $\mathcal{P}$. This paper develops the statistical theory that makes the word "reliable" precise for such
estimators. We decompose
estimator variance into a persona-draw component $\sigma_P^2$ and a within-run component $\sigma_w^2$, give unbiased ANOVA
estimators of both, and derive the variance-optimal allocation of a fixed compute budget between outer persona draws and inner replications. A coupling-based stability bound quantifies how misestimation of $\mathcal{P}$ and error in the trained policy propagate into the estimand, yielding a three-term total-error budget whose terms are separately estimable; a uniform-in-horizon version holds under a Doeblin condition on the
market chain. The main contribution is an identification theory for heterogeneous news reaction: under a fixed response nonlinearity, the aggregate impact curve $A(z)=\mathbb{E}_Q[g(\eta z)]$ detects heterogeneous news sensitivity through a strict Jensen gap and identifies the distribution $Q$ locally via odd moments and Hausdorff determinacy, with sharp failure when the response family is unknown. We provide $\sqrt{n}$-consistent
estimators and a boundary-corrected test of homogeneous news reaction. Two separation
theorems delimit when PTMC is provably preferable to homogeneous-population simulators and reduced-form forecasters, formalizing an irreducible Jensen bias floor and the Lucas critique as a minimax limit on intervention extrapolation. All proofs are given in full; guarantees are classified as unconditional (Monte Carlo convergence), conditional worst-case (the error budget), or open (the large-$K$ mean-field limit).
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Machine Learning
Measuring What Matters: A Unified Evaluation Framework for GNN Explainability
Francesco Paolo Nerini, Mirko Zaffaroni, Paolo Baracco et al. (+2 more)
Graph eXplainable AI (G-XAI) is increasingly important for making Graph Neural Networks interpretable and accountable. While a growing number of explainers are available, choosing the right method and assessing the trustworthiness of its outputs remains unclear. Consistent evaluation practices and actionable guidance are still missing, hindering practical adoption. In this paper, we introduce a unified, quantitative benchmarking framework for G-XAI that requires no ground-truth assumptions. We formalize tabular explainability metrics for graph data, evaluating topological structure and node features as independent components. Our large-scale benchmarking study identifies explainers that consistently lie on the Pareto front across metric pairs and tasks, establishing robustly non-dominated solutions - while confirming that no single explainer achieves universal superiority. We distill our findings into actionable G-XAI usability guidelines to support Machine Learning practitioners in evaluating and deploying trustworthy GNN-based pipelines.
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All authors Francesco Paolo Nerini, Mirko Zaffaroni, Paolo Baracco, Gabriele Ciravegna, Alan Perotti
Machine Learning · Cross-listed from quant-ph
Breaking the One-Dimensional Expressibility-Trainability Tradeoff
Kyoungho Cho, Yu-Seong Jeon, Jinhyoung Lee et al. (+1 more)
Expressive parameterized
quantum circuits (PQCs) are often designed under a dilemma: the growth of expressibility and entangling power (EP) that improves
Hilbert-space coverage is also expected to randomize an ansatz and activate barren-plateau (BP) conditions. We show that this dilemma is not a one-dimensional tradeoff. The usual picture collapses three inequivalent objects – parameter-ensemble coverage, fixed-
circuit entangling response, and local gradient moments – into one scalar narrative. For a fixed
circuit probed by Haar-product inputs, EP is a global two-copy mean of the output-
entanglement distribution, whereas entangling-power deviation (EPD) is a global four-copy fluctuation descriptor. Gradient variance, however, is a local two-copy contraction selected by a parameter light cone and a cost observable. This moment hierarchy yields an analytic separation: equal EP need not imply equal trainability, as witnessed by equal-EP
circuits with different EPDs and different gradient variances. These separations turn EP and EPD into a two-dial design rule for PQC ansatzes: EP measures how far the
circuit has moved along the coverage dial, while EPD monitors whether input-dependent variability remains. We find that ansatz routes can reach high, Haar-like coverage before EPD and gradient variance collapse, showing that coverage and BP activation are distinct crossover events. The EP/EPD framework thus breaks the apparent one-dimensional expressibility-trainability tradeoff into a practical design rule: search for highly expressive PQCs in the window where coverage is high but BP-like homogenization has not yet erased trainable structure.
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All authors Kyoungho Cho, Yu-Seong Jeon, Jinhyoung Lee, Jeongho Bang
Machine Learning
Minimum Block Width for Universal Approximation by Residual Neural Networks with Inner Width One
Qi Zhou, Xuan Zhou and Xiao-Song Yang
In this paper, we study the universal approximation property of residual neural networks. For input and output dimensions $d_x$ and $d_y$, and LeakyReLU, ReLU, ReLU-like activation functions, the upper and lower bounds of the minimum block width are established. To achieve $L^p$ approximation $(1\leq p <+\infty)$ on any compact set, we show that the exact minimum block width is $\max\{d_x,d_y\}$ when each residual branch has inner width 1. Furthermore, we show that residual neural networks with block width $\min\{d_x+d_y, \max\{2d_x+1,d_y\}\}$ can achieve uniform approximation on any compact set under the constraint that each residual branch has inner width 1. Besides, for any activation function family, we prove that there exist functions that cannot be approximated by residual neural networks with block width less than $\max\{d_x, d_y\}$, both in the $L^p$ sense and the uniform sense, regardless of inner width. Consequently, for LeakyReLU, ReLU, ReLU-like activation functions and $d_y\geq 2d_x+1$, the exact minimum block width for uniform approximation is $d_y$ when each residual branch has inner width 1.
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Machine Learning
Score Distributions, Not Cells: Evaluating Single-Cell Perturbations Under Class Overlap
Youssef Marrakchi, Davide D'Ascenzo and Sebastiano Cultrera di Montesano
Most classification problems assume the classes are roughly separable, so that an individual sample can usually be assigned to one class. Single-
cell perturbation data violates this assumption: two perturbations can produce different populations of
cells while overlapping so much that an individual
cell could belong to either. Per-
cell accuracy then measures this overlap rather than model quality. We see this on Tahoe-100M and the Virtual
Cell Challenge, where a linear classifier, an MLP, and a
Transformer all plateau near macro-F1 0.2-0.3 even though almost every pair of perturbations is statistically distinguishable. The fix is to score perturbations across the whole population rather than
cell by
cell. We average a classifier's per-
cell probability vectors over all
cells of a perturbation to form a population profile, then rank candidate perturbations by this profile; we call the resulting score the Classifier Discrimination Score (CDS). Taking the top-ranked class recovers the winning perturbation. It needs no retraining, costs linear time in the number of
cells, and recovers near-perfect identification from the same weak models. CDS differs from the pseudobulk-based Perturbation Discrimination Score (PDS) used in recent
benchmarks only in where the average is taken, raw gene expression for PDS versus a learned discriminative space for CDS, and identifies the true perturbation more reliably on both
datasets, with the gap widening as
cells grow scarce. Because a metric that misranks the ground truth will misrank the models scored against it, per-
cell accuracy and raw-pseudobulk scores should be used with caution when comparing perturbation models.
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Machine Learning · Cross-listed from cs.CL
MTEB-BR: A Text Embedding Benchmark for Brazilian Portuguese
Tardelli Ronan Coelho Stekel
Text
embeddings for Portuguese have no dedicated
benchmark: evaluation rests on translated corpora such as English MS MARCO or on thin
multilingual coverage, with native tasks scattered and unconsolidated. We introduce MTEB-BR, a
benchmark of 22 native Brazilian-Portuguese tasks across seven categories (classification, multilabel classification, pair classification, semantic textual similarity, clustering,
retrieval, and reranking), admitting only data created or found in Portuguese and excluding translations by construction. We evaluate 93 models spanning 23M to 27B parameters: 73 open-weight and 20 closed commercial APIs. Alongside the leaderboard we report a statistical layer for every headline comparison: per-task bootstrap confidence intervals, paired-bootstrap significance, a task- and instance-level discrimination analysis (how sharply each task separates models) adapted from Item Response Theory, and a cross-leaderboard correlation. Three findings stand out. The
benchmark cleanly separates about a dozen tiers of models, though the top six are statistically too close to order. An openly licensed, self-hostable model reaches that leading tier, so strong Portuguese
embedding quality does not require a commercial API. And a model's rank on the global
multilingual leaderboard predicts its Portuguese rank only moderately (Spearman rho = 0.75 over 55 shared models; one model ranks 3rd there and 49th here), so a native
benchmark measures something the
multilingual boards do not. We release every task, our code, and a public leaderboard, so practitioners can choose Portuguese
embedding models on native evidence.
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Machine Learning
Beyond the Need for Speed: Energy-Aware Code Generation via Simulation-Guided Reinforcement Learning
Saurabhsingh Rajput and Tushar Sharma
Code models strictly prioritize functional correctness, leaving software energy efficiency as an unoptimized byproduct. Training models to generate energy-efficient code requires reproducible feedback at scale, which physical hardware measurement cannot reliably provide due to variance. In this paper, we replace hardware profiling with a deterministic architectural simulation harness to build Green Tea, a corpus of $3.5$ million evaluations across $1{,}474$ C++ problems. We train an energy-aware code model via supervised fine-tuning on energy-contrastive pairs, followed by closed-loop reinforcement learning (GRPO) using simulation-in-the-loop feedback. To rigorously evaluate deployment readiness, we introduce the Correctness-Adjusted Reduction in Energy Total (CARET), a metric that explicitly penalizes code that sacrifices functionality for efficiency. On $143$ held-out problems, our simulation-in-the-loop pipeline achieves $12.63\%$ CARET, nearly tripling the gain of fine-tuning alone, and successfully beats the energy efficiency of human-expert references on $58.4\%$ of its valid outputs. Furthermore, our analysis exposes the IPC trap: standard throughput proxies like Instructions-Per-Cycle (IPC) actively misrank true energy efficiency on $67.8\%$ of problems, proving the absolute necessity of direct energy simulation. By releasing our
dataset and infrastructure, we bypass the $263{,}000$ CPU-hours required for reproduction, structurally empowering the community to deploy inherently energy-efficient code generation models.
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Machine Learning
A Few Teacher Steps Go a Long Way: Cost-Efficient On-Policy Data Augmentation for Agent Post-Training
Junze Ye, Jiayi Cheng, Miao Lu et al. (+3 more)
For LLM
agents, supervised fine-tuning is not only about teacher labels' quality, but also about which interaction contexts those labels condition on. Pure behavioral cloning uses full teacher demonstrations, creating a mismatch between teacher-induced contexts seen in training and student-induced contexts encountered at test time. Recent work addresses this mismatch by querying a teacher at contexts reached by the student, often with increasingly elaborate filtering of the teacher's continuations. We instead frame on-policy data construction as a budget-allocation problem: under matched supervision resources, should teacher output be spent on more start-to-finish demos, longer continuations, outcome filtering, or broader coverage of learner-induced contexts? We formalize this design space through the rollout policy, switch-time distribution, continuation horizon, filtering rules, and two complementary costs: teacher inference generated before filtering and teacher supervision retained for SFT. Across HotpotQA, ALFWorld, and Terminal-Bench-Dev, bounded unfiltered teacher continuations at learner-induced contexts improve over pure behavioral cloning at matched budgets. On HotpotQA and ALFWorld, where we run the full comparison, few-step continuations match or exceed success-filtered and critical-context-filtered alternatives. Our findings suggest that a few teacher steps, placed at learner-induced contexts, can be a more cost-efficient supervision allocation than longer or more heavily curated teacher completions.
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All authors Junze Ye, Jiayi Cheng, Miao Lu, Michal Mankowski, Jose Blanchet, Mohsen Bayati
Machine Learning · Cross-listed from cs.AI
Context-Masked Truncated Reasoning Audits for Answer-Key Dependence in LLM Tutors
Bonan Shen, Dingyan Shang, Youting Wang et al. (+2 more)
Large
language model (LLM) tutors may have access to teacher notes, answer keys, rubrics, or retrieved solutions while producing student-facing explanations. We study whether truncated
reasoning probes can distinguish direct access to such private context from answer information carried by the written explanation. Using Truncated
Reasoning AUC Evaluation (TRACE), we evaluate 1000 GSM8K problems under question-only, correct answer-key, and wrong answer-key contexts. When forced-answer probes retain the private key, answer-key TRACE AUC rises from 0.375 to 0.900, and the gold answer is recoverable with no explanation at all in 998 of 1000 cases. We then introduce a context-masked replay: answer-key-generated prefixes are probed under the corresponding question-only
prompt. Masking reduces 10% prefix accuracy from 0.997 to 0.126 and median AUC from 0.900 to 0.375, nearly matching question-only values of 0.113 and 0.375. On 746 pairs where both explanations end correctly, the masked mean AUC difference is $-0.0086$ with a 95% bootstrap interval spanning zero. Wrong keys still account for 272 of 387 incorrect final responses, showing that private artifacts can influence outputs even when early-prefix evidence disappears after masking. These results establish context masking as necessary for attributing early answer availability to an explanation rather than its hidden input.
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All authors Bonan Shen, Dingyan Shang, Youting Wang, Tao Ning, Bowen Liu
Machine Learning · Cross-listed from cs.CL
EEG-SpikeAgent: Agentic Closed-Loop Program Synthesis for Automated EEG Spike Detection
Sonali Santhosh, Kelly Shuhong Yu, Eugene Chang et al. (+3 more)
Automated detection of interictal epileptiform discharges in scalp electroencephalography (
EEG) is clinically important, but recent high-performing deep-learning models often trade interpretability for accuracy. We introduce
EEG-SpikeAgent, a closed-loop program-synthesis framework that uses a large
language model (LLM) agentic system to generate signal-processing features for spike detection in scalp
EEG. The system iteratively proposes one deterministic
EEG feature module at a time, executes the resulting code on
EEG to generate tabular features, evaluates performance via a tabular classifier, summarizes run-level metrics, and feeds structured diagnostics back to the model for refinement. Across iterations,
EEG-SpikeAgent proposes and refines candidate signal features and decision rules informed by model performance. We evaluated
EEG-SpikeAgent on VEPISET, a public 29-channel
dataset of 4-second epochs containing 2,516 discharge-containing and 22,933 non-discharge epochs. Across five-fold cross-validation with a gradient-boosted tree classifier,
agent-generated features achieved an area under the receiver operating characteristic curve of 0.935, balanced accuracy of 0.699, F1 score of 0.557, sensitivity of 0.401, and specificity of 0.996 at the default operating point. At an operating point with sensitivity 0.80, mean precision was 0.470 and mean specificity was 0.900. Artifact-aware feature generation improved balanced accuracy and F1 score over spike-only feature search. These results indicate that LLM-based program synthesis can automate
EEG feature engineering in auditable and inspectable code-driven manner for clinical and methodological review.
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All authors Sonali Santhosh, Kelly Shuhong Yu, Eugene Chang, Jonathan Kim, Kie Shidara, Danilo Bernardo
Machine Learning
Predicting Therapeutic Outcome via Aligning Patient-Specific Knowledge Graph and Gene-Level Perturbation Representations
Dongmin Bang, Sugyun An, Inyoung Sung et al. (+3 more)
Accurate prediction of patient-specific therapeutic response from pre-treatment transcriptomes is hindered by the scarcity of matched clinical response labels and post-treatment molecular profiles. Preclinical transfer-learning models can simulate drug-induced expression changes but are often hard to interpret and unstable, whereas knowledge-graph methods provide mechanistic context yet remain static and fail to capture drug-induced transcriptomic perturbation dynamics. We propose PREDIKTOR, a patient-centered multi-view framework that aligns a personalized network view with a transferable transcriptomic perturbation view to predict clinical drug response. For each patient, we construct an individualized gene regulatory network from tumor expression using DysRegNet and augment it with drug-target links from DrugBank; a graph neural encoder yields a drug-centric, mechanistically grounded
embedding. In parallel, a frozen condition-specific gene-gene
attention model pretrained on LINCS L1000 generates a simulated post-perturbation transcriptomic profile for the same patient-drug pair. We align the two views in a shared latent space via a CLIP-style contrastive objective with drug-context hard negatives, then concatenate the representations for end-to-end response classification. On TCGA, PREDIKTOR consistently outperforms state-of-the-art baselines under patient-, drug-, and tissue-split evaluations, and transfers zero-shot to the I-SPY2 trial, improving AUROC by 5.6% over competing methods. The aligned
embeddings yield stable gene and pathway attributions that recover known mechanisms, supporting actionable and interpretable precision oncology.
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All authors Dongmin Bang, Sugyun An, Inyoung Sung, Ilho Yun, Sun Kim, Sangseon Lee