Daily Papers

Protein language models (PLMs) encode rich biological information, yet their internal neuron representations are poorly understood. We introduce the first automated framework for labeling every neuron in a PLM with biologically grounded natural language descriptions. Unlike prior approaches relying on sparse autoencoders or manual annotation, our method scales to hundreds of thousands of neurons, revealing individual neurons are selectively sensitive to diverse biochemical and structural properties. We then develop a novel neuron activation-guided steering method to generate proteins with desired traits, enabling convergence to target biochemical properties like molecular weight and instability index as well as secondary and tertiary structural motifs, including alpha helices and canonical Zinc Fingers. We finally show that analysis of labeled neurons in different model sizes reveals PLM scaling laws and a structured neuron space distribution.

We introduce ProofGrid, a benchmark suite for evaluating LLM reasoning through machine-checkable proofs rather than final answers alone. ProofGrid contains 15 tasks spanning proof writing, proof checking, proof masking, and proof gap-filling. Tasks are expressed in minimal formal notation, especially NDL, a compact natural-deduction language that fits in short prompts and supports precise, auditable verification. This yields mechanical, reproducible, and fine-grained evaluation rather than judgments by humans or LLMs. ProofGrid covers a calibrated difficulty spectrum, from foundational reasoning tests to structurally rich challenge tasks that no current model solves, while minimizing reliance on domain knowledge, solver delegation, and long-context artifacts. We also develop a comparative framework for reasoning benchmarks and use it to situate ProofGrid relative to existing work in terms of representation, verification guarantees, and reasoning depth. Methodologically, we introduce an instrumented proof-checking pipeline that tolerates minor surface deviations while locating the first substantive reasoning failure, improving measurement resolution and separating proof planning from low-level execution noise. Using this pipeline, we evaluate a broad range of open and proprietary models. Results show rapid progress but substantial remaining limits: frontier models perform well on several foundational tasks, yet difficult tasks, especially those requiring global combinatorial reasoning or low-level proof synthesis, remain far from solved. We also identify epistemic instability, where models generate flawed proofs yet correctly reject those local inferences in isolation, and formalize this with an Epistemic Stability Index. Finally, we complement accuracy with 2PL IRT analyses, Wright maps, and a normalized task-discrimination measure based on Fisher information.

Genome engineering has achieved remarkable sequence-level precision, yet predicting the transcriptomic state that a cell will occupy after perturbation remains an open problem. Single-cell CRISPR screens measure how far cells move from their unperturbed state, but this effect magnitude ignores a fundamental question: do the cells move together? Two perturbations with identical magnitude can produce qualitatively different outcomes if one drives cells coherently along a shared trajectory while the other scatters them across expression space. We introduce a geometric stability metric, Shesha, that quantifies the directional coherence of single-cell perturbation responses as the mean cosine similarity between individual cell shift vectors and the mean perturbation direction. Across five CRISPR datasets (2,200+ perturbations spanning CRISPRa, CRISPRi, and pooled screens), stability correlates strongly with effect magnitude (Spearman ρ=0.75-0.97), with a calibrated cross-dataset correlation of 0.97. Crucially, discordant cases where the two metrics decouple expose regulatory architecture: pleiotropic master regulators such as CEBPA and GATA1 pay a "geometric tax," producing large but incoherent shifts, while lineage-specific factors such as KLF1 produce tightly coordinated responses. After controlling for magnitude, geometric instability is independently associated with elevated chaperone activation (HSPA5/BiP; ρ_{partial}=-0.34 and -0.21 across datasets), and the high-stability/high-stress quadrant is systematically depleted. The magnitude-stability relationship persists in scGPT foundation model embeddings, confirming it is a property of biological state space rather than linear projection. Perturbation stability provides a complementary axis for hit prioritization in screens, phenotypic quality control in cell manufacturing, and evaluation of in silico perturbation predictions.

Reasoning failures in large language models (LLMs) are typically measured only at the end of a generation, yet many failures manifest as a process-level breakdown: the model "loses the thread" mid-reasoning. We study whether such breakdowns are detectable from inference-time observables available in standard APIs (token log probabilities), without any training or fine-tuning. We define a simple instability signal that combines consecutive-step distributional shift (JSD) and uncertainty (entropy), summarize each trace by its peak instability strength, and show that this signal reliably predicts failure. Across GSM8K and HotpotQA, instability strength predicts wrong answers with above-chance AUC and yields monotonic bucket-level accuracy decline at scale across model sizes. Crucially, we show that instability is not uniformly harmful: early instability can reflect subsequent stabilization and a correct final answer (corrective instability), whereas late instability is more often followed by failure (destructive instability), even at comparable peak magnitudes, indicating that recoverability depends not only on how strongly the distribution changes but also on when such changes occur relative to the remaining decoding horizon. The method is model-agnostic, training-free, and reproducible, and is presented as a diagnostic lens rather than a corrective or control mechanism.

Pathology Foundation Models (FMs) hold great promise for healthcare. Before they can be used in clinical practice, it is essential to ensure they are robust to variations between medical centers. We measure whether pathology FMs focus on biological features like tissue and cancer type, or on the well known confounding medical center signatures introduced by staining procedure and other differences. We introduce the Robustness Index. This novel robustness metric reflects to what degree biological features dominate confounding features. Ten current publicly available pathology FMs are evaluated. We find that all current pathology foundation models evaluated represent the medical center to a strong degree. Significant differences in the robustness index are observed. Only one model so far has a robustness index greater than one, meaning biological features dominate confounding features, but only slightly. A quantitative approach to measure the influence of medical center differences on FM-based prediction performance is described. We analyze the impact of unrobustness on classification performance of downstream models, and find that cancer-type classification errors are not random, but specifically attributable to same-center confounders: images of other classes from the same medical center. We visualize FM embedding spaces, and find these are more strongly organized by medical centers than by biological factors. As a consequence, the medical center of origin is predicted more accurately than the tissue source and cancer type. The robustness index introduced here is provided with the aim of advancing progress towards clinical adoption of robust and reliable pathology FMs.

Prediction models can exhibit sensitivity with respect to training data: small changes in the training data can produce models that assign conflicting predictions to individual data points during test time. In this work, we study this sensitivity in recommender systems, where users' recommendations are drastically altered by minor perturbations in other unrelated users' interactions. We introduce a measure of stability for recommender systems, called Rank List Sensitivity (RLS), which measures how rank lists generated by a given recommender system at test time change as a result of a perturbation in the training data. We develop a method, CASPER, which uses cascading effect to identify the minimal and systematical perturbation to induce higher instability in a recommender system. Experiments on four datasets show that recommender models are overly sensitive to minor perturbations introduced randomly or via CASPER - even perturbing one random interaction of one user drastically changes the recommendation lists of all users. Importantly, with CASPER perturbation, the models generate more unstable recommendations for low-accuracy users (i.e., those who receive low-quality recommendations) than high-accuracy ones.

Nowadays, software systems tend to include Artificial Intelligence (AI) components. Changes in the operational environment have been known to negatively impact the stability of AI-enabled software systems by causing unintended changes in behavior. However, how an environment configuration impacts the behavior of such systems has yet to be explored. Understanding and quantifying the degree of instability caused by different environment settings can help practitioners decide the best environment configuration for the most stable AI systems. To achieve this goal, we performed experiments with eight different combinations of three key environment variables (operating system, Python version, and CPU architecture) on 30 open-source AI-enabled systems using the Travis CI platform. We determine the existence and the degree of instability introduced by each configuration using three metrics: the output of an AI component of the system (model performance), the time required to build and run the system (processing time), and the cost associated with building and running the system (expense). Our results indicate that changes in environment configurations lead to instability across all three metrics; however, it is observed more frequently with respect to processing time and expense rather than model performance. For example, between Linux and MacOS, instability is observed in 23\%, 96.67\%, and 100\% of the studied projects in model performance, processing time, and expense, respectively. Our findings underscore the importance of identifying the optimal combination of configuration settings to mitigate drops in model performance and reduce the processing time and expense before deploying an AI-enabled system.

Recent studies empirically demonstrate the positive relationship between the transferability of neural networks and the within-class variation of the last layer features. The recently discovered Neural Collapse (NC) phenomenon provides a new perspective of understanding such last layer geometry of neural networks. In this paper, we propose a novel metric, named Variability Collapse Index (VCI), to quantify the variability collapse phenomenon in the NC paradigm. The VCI metric is well-motivated and intrinsically related to the linear probing loss on the last layer features. Moreover, it enjoys desired theoretical and empirical properties, including invariance under invertible linear transformations and numerical stability, that distinguishes it from previous metrics. Our experiments verify that VCI is indicative of the variability collapse and the transferability of pretrained neural networks.

Large language models (LLMs) are increasingly deployed in settings where reasoning, such as multi-step problem solving and chain-of-thought, is essential. Yet, current evaluation practices overwhelmingly report single-run accuracy while ignoring the intrinsic uncertainty that naturally arises from stochastic decoding. This omission creates a blind spot because practitioners cannot reliably assess whether a method's reported performance is stable, reproducible, or cost-consistent. We introduce ReasonBENCH, the first benchmark designed to quantify the underlying instability in LLM reasoning. ReasonBENCH provides (i) a modular evaluation library that standardizes reasoning frameworks, models, and tasks, (ii) a multi-run protocol that reports statistically reliable metrics for both quality and cost, and (iii) a public leaderboard to encourage variance-aware reporting. Across tasks from different domains, we find that the vast majority of reasoning strategies and models exhibit high instability. Notably, even strategies with similar average performance can display confidence intervals up to four times wider, and the top-performing methods often incur higher and less stable costs. Such instability compromises reproducibility across runs and, consequently, the reliability of reported performance. To better understand these dynamics, we further analyze the impact of prompts, model families, and scale on the trade-off between solve rate and stability. Our results highlight reproducibility as a critical dimension for reliable LLM reasoning and provide a foundation for future reasoning methods and uncertainty quantification techniques. ReasonBENCH is publicly available at https://github.com/au-clan/ReasonBench .