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Nithin Parsan

Publications and source records attributed to Nithin Parsan.

4 recordsLinked to original sources

BenchBench-Protocol: Evaluating Real-World Wet-Lab Protocol Reasoning and Modification

We introduce BenchBench-Protocol, a benchmark for large language models of 149 protocol-modification tasks recovered from modifications that scientists made to published protocols during real experimental work. Adapting a published protocol to a new experiment is a routine task for a wet-lab scientist, and a correct modification requires accounting for prior choices and downstream steps. Recent life-science benchmarks have moved toward open-ended, rubric-graded tasks, but tasks are typically elicited from experts rather than reconstructed from real-world modifications. BenchBench-Protocol tasks are derived from differences between a published protocol and a version a scientist modified, which provides the basis for the query and the weighted rubric elements for a correct response. The benchmark draws from 96 source protocols across nine domains of wet-lab biology and only includes tasks rated highly after review by domain experts. We evaluate nine closed and open models; Claude Opus 5 scores highest at 59.2% normalized rubric score, with other models between 34.1% and 47.1%, and the benchmark remains unsaturated when taking the best of ten attempts. As models are increasingly helpful in life-sciences research, evaluating them on routine wet-lab tasks becomes correspondingly important. We present BenchBench-Protocol as both a grounded assessment of wet-lab reasoning and evidence for the utility of real-world experiments to construct benchmark tasks.

cs.AI

Mechanistic Interpretability of Antibody Language Models Using SAEs

Sparse autoencoders (SAEs) are a mechanistic interpretability technique that have been used to provide insight into learned concepts within large protein language models. Here, we employ TopK and Ordered SAEs to investigate autoregressive antibody language models, and steer their generation. We show that TopK SAEs can reveal biologically meaningful latent features, but high feature-concept correlation does not guarantee causal control over generation. In contrast, Ordered SAEs impose a hierarchical structure that reliably identifies steerable features, but at the expense of more complex and less interpretable activation patterns. These findings advance the mechanistic interpretability of domain-specific protein language models and suggest that, while TopK SAEs suffice for mapping latent features to concepts, Ordered SAEs are preferable when precise generative steering is required.

cs.LG

Enforcing Orderedness to Improve Feature Consistency

Sparse autoencoders (SAEs) have been widely used for interpretability of neural networks, but their learned features often vary across seeds and hyperparameter settings. We introduce Ordered Sparse Autoencoders (OSAE), which extend Matryoshka SAEs by (1) establishing a strict ordering of latent features and (2) deterministically using every feature dimension, avoiding the sampling-based approximations of prior nested SAE methods. Theoretically, we show that OSAEs resolve permutation non-identifiability in settings of sparse dictionary learning where solutions are unique (up to natural symmetries). Empirically on Gemma2-2B and Pythia-70M, we show that OSAEs can help improve consistency compared to Matryoshka baselines.

cs.LG

Towards Interpretable Protein Structure Prediction with Sparse Autoencoders

Protein language models have revolutionized structure prediction, but their nonlinear nature obscures how sequence representations inform structure prediction. While sparse autoencoders (SAEs) offer a path to interpretability here by learning linear representations in high-dimensional space, their application has been limited to smaller protein language models unable to perform structure prediction. In this work, we make two key advances: (1) we scale SAEs to ESM2-3B, the base model for ESMFold, enabling mechanistic interpretability of protein structure prediction for the first time, and (2) we adapt Matryoshka SAEs for protein language models, which learn hierarchically organized features by forcing nested groups of latents to reconstruct inputs independently. We demonstrate that our Matryoshka SAEs achieve comparable or better performance than standard architectures. Through comprehensive evaluations, we show that SAEs trained on ESM2-3B significantly outperform those trained on smaller models for both biological concept discovery and contact map prediction. Finally, we present an initial case study demonstrating how our approach enables targeted steering of ESMFold predictions, increasing structure solvent accessibility while fixing the input sequence. To facilitate further investigation by the broader community, we open-source our code, dataset, pretrained models https://github.com/johnyang101/reticular-sae , and visualizer https://sae.reticular.ai .

q-bio.BM