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Niloofar Yousefi

Publications and source records attributed to Niloofar Yousefi.

At least 19 recordsLinked to original sources

Beyond Tokens: Probing Higher-Order Epistasis in Learned Protein Representations

Protein fitness landscapes contain nonlinear interactions in which mutation effects depend on other residues. We introduce ORBIT, an Order-Resolved Benchmarking of Interaction Transformations framework that separates interaction presence, representation accessibility, and functional recovery. ORBIT first validates Walsh-based diagnostics on synthetic landscapes with known interaction order, then analyzes the experimentally measured GB1 fitness landscape under the FLIP 2-vs-rest setting. We compare ridge regression, a standard MLP, independent tokens, nonlinear independent tokens, and Residual Interaction Tokenization (RIT). Across 20 paired training seeds, the primary two-hidden-layer comparison found no significant architecture differences in FLIP test R^2, third- or fourth-order functional recovery, or final-layer third- or fourth-order accessibility. However, RIT significantly increased pairwise accessibility at the token stage relative to both independent-token controls (Delta A_tok,2 = 0.2468, d_z = 1.67, Holm-adjusted p = 1.14 x 10^-5), without a detectable downstream higher-order advantage. A pre-specified depth/capacity analysis showed that deeper MLPs improved FLIP prediction, third-order functional recovery, and final-layer third-order accessibility; fourth-order accessibility also improved relative to the shallow MLP but remained below zero in absolute held-out R^2. ORBIT therefore reveals representation-level changes hidden by conventional prediction metrics and distinguishes early interaction-aware encoding from higher-order structure constructed by downstream nonlinear capacity.

q-bio.QM

Can We Trust In-Distribution Success? Locked Evaluation Reveals Transfer Failure and Sampling-Depth Entanglement in CRISPRi Perturbation Prediction

AI evaluation can support the wrong inference when an in-domain benchmark success does not survive distribution shift, or when the benchmark endpoint is entangled with a design factor. We study this problem in CRISPRi perturbation-effect prediction, evaluating a frozen Geneformer representation under a locked, pre-registered protocol: heads and model selection were frozen before test evaluation; the protocol required external outcome labels to remain withheld until final unblinding; and analysis-governing decisions were fixed before the evaluations they govern. In-distribution on the Virtual Cell Challenge (VCC), the frozen representation carries measurable predictive information beyond a dimension-matched random-feature control (Delta R^2 = +0.1645, 95% CI [+0.1375, +0.1920]), satisfying the pre-registered informativeness gate required before interpreting transfer. It then fails zero-shot transfer on both external screens (Spearman rho = -0.139 and -0.267), lying below that control on each. Adding a predefined magnitude block improves the representation externally (Delta rho = +0.032 and +0.143) but, under the frozen primary head, does not rescue transfer: both remain negative. A pre-registered, count-adjusted max-response secondary is positively associated with the outcome on both screens; we report it as correlational and secondary, not as a recovered magnitude signal. Finally, the VCC endpoint is strongly sample-size associated: a count-only linear model reaches R^2 = +0.4325, versus +0.2589 for the four magnitude scalars; adding those scalars to cell count improves R^2 by only +0.0017, so much of the aggregate-magnitude signal overlaps with cell count. This case study shows how locking the evaluation, harmonizing the measured endpoint, and separating primary from secondary evidence can change the inference supported by an AI benchmark.

cs.LG

BRIDGE: Bottleneck-Aware Regulator-Set Inference and Diagnosis for Cooperative Gene Regulatory Recovery

Cooperative gene regulation often depends on groups of regulators acting jointly, but most gene regulatory network (GRN) inference methods output pairwise regulator-target rankings. We introduce Bottleneck-Aware Regulator-Set Inference and Diagnosis (BRIDGE), a framework for complete regulator-set recovery, and Targeted Recovery Attribution for Cooperative Evaluation (TRACE), a diagnostic suite that attributes failures to retrieval, set-level scoring, decoding, and evaluation bottlenecks. TRACE includes a leak-free mechanism-mismatch cooperativity stress test in which cooperative targets are generated by random nonlinear mechanisms rather than product interactions. This design avoids feature-mechanism circularity: Residual higher-order set scoring (Residual HOS2) operates on raw expression vectors without handcrafted product-correlation features. Across 30 matched seed-cooperativity settings, Residual HOS2 improves Jaccard similarity from 0.382 to 0.460, recall from 0.522 to 0.597, and exact recovery from 0.053 to 0.113 over a decomposable pairwise set scorer (PairS2), although exact recovery remains low. On SERGIO DS3, oracle retrieval and TRACE show that candidate coverage is necessary but insufficient because set-level misranking remains the dominant source of exact-recovery failure. PairS2 proposal followed by Residual HOS2 reranking reduces HOS2-scored candidate sets by 94-97% while largely preserving exact-recovery behavior. These results distinguish edge ranking, candidate retrieval, set-level scoring, and exact cooperative regulator-set recovery as separate objectives.

cs.LG

Pre-Registered External Evaluation Yields a Consistent Partial-Replication Category across Three Transcriptomic Foundation Models

Transcriptomic foundation models are increasingly used as reusable cell and gene representations, but validating them on new data under weak supervision and distribution shift is hard: standard comparisons conflate genuine representation signal with model capacity, row-identity artifacts, gains over strong task-specific baselines, and outcome rules chosen after seeing the test set. We introduce a pre-registered, final-test-once evaluation framework that locks the outcome rule, seeds, and target-gene-grouped splits before any test data are seen, and scores each frozen representation against a strong expression baseline, a matched-capacity Gaussian control, and a within-split row-identity (shuffle) control; only the per-cell embedding-extraction step is model-specific. Applying it to three architecturally distinct models-Geneformer, scGPT, and UCE-across two external Replogle Perturb-seq datasets (RPE1 and K562), all three clear the capacity and row-identity controls by a wide margin, yet none reliably beats the expression baseline: the strongest (Geneformer) exceeds it by at most about $0.03$ test $R^2$ and clears the pre-registered four-of-five-seed threshold in neither dataset, while scGPT and UCE fall below it. All three therefore land in the same pre-registered partial-replication category-a consistent cross-architecture outcome, even though the baseline-relative gap differs in sign and magnitude across models. These representations carry real structure beyond trivial controls but, under this weak magnitude label, do not transfer past a simple strong baseline; the locked framework is reusable for any frozen transcriptomic representation by swapping only the extraction step.

q-bio.OT

Adaptive Multi-Expert Graph Transformer for Interpretable EEG-Based Diagnostics

Electroencephalographic (EEG) abnormalities arise from dynamic changes in neural synchrony across spatial and temporal scales, yet many computational approaches reduce these dynamics to static features. We present a Spatial Multi-Expert Graph Transformer that models each EEG recording as a sequence of dynamic functional connectivity graphs. Time-resolved connectivity is estimated using the weighted Phase Lag Index (wPLI), and hierarchical graph encoding aggregates information from electrode to regional and global levels. A multi-expert transformer architecture enables subtype-aware reasoning, with a gating mechanism adaptively fusing expert outputs for global abnormality prediction. Experiments on the TUAB dataset show competitive abnormal EEG detection performance and demonstrate the potential of dynamic graph modeling with adaptive expert fusion for interpretable, subtype-aware spatial--temporal analysis.

cs.LG

Right Knowledge, Wrong Answer: Characterizing Parametric Temporal Conflict in Open-Weight Language Models

Language models may encode both outdated facts and their newer replacements. We introduce Parametric Temporal Conflict (PTC), where the newer fact is present and recoverable, but the default forward pass prefers the outdated one. We release a deterministically verified benchmark of 8,746 Wikidata position-holder transitions and evaluate four open-weight language models across three families. A date-prefix prompt recovers the newer fact in 61-81% of PTC cases. Activation patching flips predictions in 72-85% of cases and localizes the preference to model-specific upper-layer regions. Residual-stream steering outperforms norm-matched random directions, indicating direction-specific representations. These results show that PTC reflects a localized representational preference rather than missing knowledge. Recovery is measured on oracle-identified conflicts because automatic detection remains unreliable. We release the benchmark, code, and statistics.

cs.LG

NEXUS: Structured Runtime Safety for Tool-Using LLM Agents

Tool-using LLM agents increasingly execute high-impact actions, making runtime safety monitoring essential. We present NEXUS (Neural EXecution Utility and Safety), a structured-plan safety monitor that applies a formal intervention policy to select among four actions: allow, block, request confirmation, or request revision. NEXUS combines deterministic safety rules, argument-level inspection, and a calibrated logistic-regression risk score for graded escalation. On a 128-instance synthetic benchmark, NEXUS achieves an F1 score of 0.949 and a 4-class intervention accuracy of 0.6406, outperforming rule-only intervention selection by 27.3 percentage points. It also improves over rule-only on R-Judge (F1 = 0.861 vs. 0.849), matches rule-only on AgentHarm due to threat-model limits, and achieves 0% ASR at 99% control allow on IPI. On the rule-blind NEXUS-Stress benchmark, NEXUS reaches an F1 score of 0.881, highlighting the difficulty of fine-grained intervention routing. With 0.205 ms median latency, NEXUS adds under 0.1% overhead to typical agent loops. Code, benchmarks, and the calibrated risk scorer are publicly released.

cs.AI

When Policies Cannot Be Retrained: A Unified Closed-Form View of Post-Training Steering in Offline Reinforcement Learning

Offline reinforcement learning (RL) can learn effective policies from fixed datasets, but deployment objectives may change after training, and in many applications the trained actor cannot be retrained because of data, cost, or governance constraints. We study deployment-time adaptation for frozen offline actors using Product-of-Experts (PoE) composition with a goal-conditioned prior. Our main practical finding is graceful degradation rather than universal performance gain: under degraded or random priors, precision-weighted composition remains anchored to the frozen actor, while additive and prior-only adaptation collapse, and a KL-budget selector often recovers a near-oracle operating point. We also make explicit a closed-form identity in the frozen-actor setting: for diagonal-Gaussian actors and priors, PoE with coefficient alpha yields the same deterministic policy as KL-regularized adaptation with beta = alpha / (1 - alpha), with posterior covariances differing only by a global scalar factor. Empirically, across four D4RL environments (3,900 MuJoCo episodes), we observe a 4/5/3 HELP/FROZEN/HURT split. Extending the analysis to six harder cells and two AntMaze diagnostics reveals an actor-competence ceiling: medium-expert remains HURT in all 9 cells at every tested alpha, while AntMaze with a behavior-cloned frozen actor yields zero success for all composition rules. Overall, PoE and KL-regularized adaptation are best viewed as a single actor-anchored safety mechanism for deployment-time steering.

cs.LG

BioDivergence: A Benchmark and Evaluation Framework for Hidden Contextual Contradictions in Biomedical Abstracts

Biomedical findings often seem to conflict across studies, but many of these differences are context-dependent rather than true contradictions. Variations in cohort, geography, assay protocol, disease subtype, and clinical setting can make both claims locally valid. Existing NLI and scientific claim-verification benchmarks reduce such cases to entailment, contradiction, or neutral, failing to capture the contextual structure behind divergence. To address this, we introduce BioDivergence, an evaluation framework with a six-class conflict taxonomy, a 13-axis divergence ontology, and four structured outputs per claim pair: conflict type, divergence axes, dominant confounder, and reconciliation explanation. We release BioDivergence-Silver-v1.0, an article-disjoint silver benchmark of 11,865 claim pairs across five biomedical domains, alongside a legacy deduplicated variant for comparison. Results show notable ranking differences between the two variants, with the fine-tuned reference model dropping about 12 points under the article-disjoint setting, while Mistral-7B-Instruct-v0.3 achieves 0.5523 accuracy and 0.3894 contextual-F1 on the 842-example primary test set. BioDivergence offers a more faithful way to distinguish contextual divergence from direct contradiction and to separate article-level memorization from genuine task learning.

cs.CL

Learning Stable Predictors from Weak Supervision under Distribution Shift

Learning from weak, proxy, or relative supervision is common when ground-truth labels are unavailable, but robustness under distribution shift remains poorly understood because the supervision mechanism itself may change across environments. We formalize this phenomenon as supervision drift, defined as changes in $P(y \mid x, c)$ across contexts, and study it in CRISPR-Cas13d transcriptomic perturbation experiments where guide efficacy is inferred indirectly from RNA-seq responses. Using publicly available data spanning two human cell lines and multiple post-induction timepoints, we construct a controlled non-IID benchmark with explicit domain (cell line) and temporal shifts, while reusing a fixed weak-label construction across all contexts to avoid changing targets. Across linear and tree-based models, weak supervision supports meaningful learning in-domain (ridge $R^2 = 0.356$, Spearman $\rho = 0.442$) and partial cross-cell-line transfer ($\rho \approx 0.40$). In contrast, temporal transfer collapses across all model classes considered, yielding negative $R^2$ and weak or near-zero $\rho$ (ridge $R^2 = -0.145$, $\rho = 0.008$; XGBoost $R^2 = -0.155$, $\rho = 0.056$; random forest $R^2 = -0.322$, $\rho = 0.139$). Additional robustness analyses using externally recomputed weak labels, shift-score quantification, and simple mitigation baselines preserve the same qualitative pattern. Feature-label association and feature-importance analyses remain relatively stable across cell lines but change sharply over time, indicating that failures arise from supervision drift rather than model capacity or simple covariate shift. These results show that strong in-domain performance under weak supervision can be misleading and motivate feature stability as a lightweight diagnostic for non-transferability before deployment.

cs.LG

BIOGEN: Evidence-Grounded Multi-Agent Reasoning Framework for Transcriptomic Interpretation in Antimicrobial Resistance

Interpreting gene clusters from RNA sequencing (RNA-seq) remains challenging, especially in antimicrobial resistance studies where mechanistic insight is important for hypothesis generation. Existing pathway enrichment methods can summarize co-expressed modules, but they often provide limited cluster-specific explanations and weak connections to supporting literature. We present BIOGEN, an evidence-grounded multi-agent framework for post hoc interpretation of RNA-seq transcriptional modules. BIOGEN combines biomedical retrieval, structured reasoning, and multi-critic verification to generate traceable cluster-level explanations with explicit evidence and confidence labels. On a primary Salmonella enterica dataset, BIOGEN achieved strong biological grounding, including BERTScore 0.689, Semantic Alignment Score 0.715, KEGG Functional Similarity 0.342, and a hallucination rate of 0.000, compared with 0.100 for an LLM-only baseline. Across four additional bacterial RNA-seq datasets, BIOGEN also maintained zero hallucination under the same fixed pipeline. In comparisons with representative open-source agentic AI baselines, BIOGEN was the only framework that consistently preserved zero hallucination across all five datasets. These findings suggest that retrieval alone is not enough for reliable biological interpretation, and that evidence-grounded orchestration is important for transparent and source-traceable transcriptomic reasoning.

q-bio.QM

Hybrid Diffusion Model for Breast Ultrasound Image Augmentation

We propose a hybrid diffusion-based augmentation framework to overcome the critical challenge of ultrasound data augmentation in breast ultrasound (BUS) datasets. Unlike conventional diffusion-based augmentations, our approach improves visual fidelity and preserves ultrasound texture by combining text-to-image generation with image-to-image (img2img) refinement, as well as fine-tuning with low-rank adaptation (LoRA) and textual inversion (TI). Our method generated realistic, class-consistent images on an open-source Kaggle breast ultrasound image dataset (BUSI). Compared to the Stable Diffusion v1.5 baseline, incorporating TI and img2img refinement reduced the Frechet Inception Distance (FID) from 45.97 to 33.29, demonstrating a substantial gain in fidelity while maintaining comparable downstream classification performance. Overall, the proposed framework effectively mitigates the low-fidelity limitations of synthetic ultrasound images and enhances the quality of augmentation for robust diagnostic modeling.

eess.IV

UAT-LITE: Inference-Time Uncertainty-Aware Attention for Pretrained Transformers

Neural NLP models are often miscalibrated and overconfident, assigning high confidence to incorrect predictions and failing to express uncertainty during internal evidence aggregation. This undermines selective prediction and high-stakes deployment. Post-hoc calibration methods adjust output probabilities but leave internal computation unchanged, while ensemble and Bayesian approaches improve uncertainty at substantial training or storage cost. We propose UAT-LITE, an inference-time framework that makes self-attention uncertainty-aware via Monte Carlo dropout in pretrained transformer classifiers. Unlike output-level calibration (e.g., TS), UAT-LITE injects epistemic uncertainty directly into attention, enabling uncertainty-aware routing during contextualization and token-level diagnostic signals beyond global logit rescaling. Token-level epistemic uncertainty is estimated from stochastic forward passes and used to modulate self-attention during contextualization, without modifying pretrained weights or training objectives. We additionally introduce a layer-wise variance decomposition to diagnose how predictive uncertainty accumulates across transformer depth. Across SQuAD 2.0 answerability, MNLI, and SST-2, UAT-LITE achieves an average relative ECE reduction of approximately 20% compared with a fine-tuned BERT-base baseline while preserving accuracy, and yields more informative uncertainty behavior for selective prediction under distribution shift.

cs.AI

Validating Interpretability in siRNA Efficacy Prediction: A Perturbation-Based, Dataset-Aware Protocol

Saliency maps are increasingly used as design guidance in siRNA efficacy prediction, yet attribution methods are rarely validated before motivating sequence edits. We introduce a pre-synthesis gate: a protocol for counterfactual sensitivity faithfulness that tests whether mutating high-saliency positions changes model output more than composition-matched controls. Cross-dataset transfer reveals two failure modes that would otherwise go undetected: faithful-but-wrong (saliency valid, predictions fail) and inverted saliency (top-saliency edits less impactful than random). Strikingly, models trained on mRNA-level assays collapse on a luciferase reporter dataset, demonstrating that protocol shifts can silently invalidate deployment. Across four benchmarks, 19/20 fold instances pass; the single failure shows inverted saliency. A biology-informed regularizer (BioPrior) strengthens saliency faithfulness with modest, dataset-dependent predictive trade-offs. Our results establish saliency validation as essential pre-deployment practice for explanation-guided therapeutic design. Code is available at https://github.com/shadi97kh/BioPrior.

q-bio.GN

MedBayes-Lite: A Clinical Uncertainty Governance Layer for Risk-Aware Medical Decision Support

Clinical language models often assign high confidence to incorrect predictions, particularly in high-severity and out-of-distribution cases. We present MedBayes-Lite, a retraining-free uncertainty governance layer for transformer-based clinical predictors. It combines Monte Carlo dropout, predictive calibration, and confidence-guided abstention to defer low-confidence predictions for human review, adding no trainable parameters. Evaluated on MedMCQA and MedQA-USMLE, MedBayes-Lite reduces expected calibration error by 0.23 to 0.33 and drives harmful overconfident errors (confident, incorrect, high-severity predictions) toward zero. Under domain shift from MedMCQA to MedQA-USMLE, it reduces confident high-severity errors from about 21% to near zero while roughly halving calibration drift. We also introduce the Clinical Uncertainty Score (CUS), which strongly correlates with harmful overconfidence (r approximately 0.88). Although the framework does not improve risk-coverage ranking, and temperature scaling or deep ensembles may provide advantages in calibration cost or risk ranking, MedBayes-Lite offers a practical calibration-and-abstention layer that reduces confident high-severity errors in clinical question-answering benchmarks.

cs.AI

FlowNIB: An Information Bottleneck Analysis of Bidirectional vs. Unidirectional Language Models

Bidirectional language models have better context understanding and perform better than unidirectional models on natural language understanding tasks, yet the theoretical reasons behind this advantage remain unclear. In this work, we investigate this disparity through the lens of the Information Bottleneck (IB) principle, which formalizes a trade-off between compressing input information and preserving task-relevant content. We propose FlowNIB, a dynamic and scalable method for estimating mutual information during training that addresses key limitations of classical IB approaches, including computational intractability and fixed trade-off schedules. Theoretically, we show that bidirectional models retain more mutual information and exhibit higher effective dimensionality than unidirectional models. To support this, we present a generalized framework for measuring representational complexity and prove that bidirectional representations are strictly more informative under mild conditions. We further validate our findings through extensive experiments across multiple models and tasks using FlowNIB, revealing how information is encoded and compressed throughout training. Together, our work provides a principled explanation for the effectiveness of bidirectional architectures and introduces a practical tool for analyzing information flow in deep language models.

cs.CL

Explainable Detection of Implicit Influential Patterns in Conversations via Data Augmentation

In the era of digitalization, as individuals increasingly rely on digital platforms for communication and news consumption, various actors employ linguistic strategies to influence public perception. While models have become proficient at detecting explicit patterns, which typically appear in texts as single remarks referred to as utterances, such as social media posts, malicious actors have shifted toward utilizing implicit influential verbal patterns embedded within conversations. These verbal patterns aim to mentally penetrate the victim's mind in order to influence them, enabling the actor to obtain the desired information through implicit means. This paper presents an improved approach for detecting such implicit influential patterns. Furthermore, the proposed model is capable of identifying the specific locations of these influential elements within a conversation. To achieve this, the existing dataset was augmented using the reasoning capabilities of state-of-the-art language models. Our designed framework resulted in a 6% improvement in the detection of implicit influential patterns in conversations. Moreover, this approach improved the multi-label classification tasks related to both the techniques used for influence and the vulnerability of victims by 33% and 43%, respectively.

cs.CL

RoCoFT: Efficient Finetuning of Large Language Models with Row-Column Updates

We propose RoCoFT, a parameter-efficient fine-tuning method for large-scale language models (LMs) based on updating only a few rows and columns of the weight matrices in transformers. Through extensive experiments with medium-size LMs like BERT and RoBERTa, and larger LMs like Bloom-7B, Llama2-7B, and Llama2-13B, we show that our method gives comparable or better accuracies than state-of-art PEFT methods while also being more memory and computation-efficient. We also study the reason behind the effectiveness of our method with tools from neural tangent kernel theory. We empirically demonstrate that our kernel, constructed using a restricted set of row and column parameters, are numerically close to the full-parameter kernel and gives comparable classification performance. Ablation studies are conducted to investigate the impact of different algorithmic choices, including the selection strategy for rows and columns as well as the optimal rank for effective implementation of our method.

cs.CL