Showing 1–9 of 9 results for author: Padigela, H

PLUTO-4: Frontier Pathology Foundation Models

Authors: Harshith Padigela, Shima Nofallah, Atchuth Naveen Chilaparasetti, Ryun Han, Andrew Walker, Judy Shen, Chintan Shah, Blake Martin, Aashish Sood, Elliot Miller, Ben Glass, Andy Beck, Harsha Pokkalla, Syed Ashar Javed

Abstract: Foundation models trained on large-scale pathology image corpora have demonstrated strong transfer capabilities across diverse histopathology tasks. Building on this progress, we introduce PLUTO-4, our next generation of pathology foundation models that extend the Pathology-Universal Transformer (PLUTO) to frontier scale. We share two complementary Vision Transformer architectures in the PLUTO-4 f… ▽ More Foundation models trained on large-scale pathology image corpora have demonstrated strong transfer capabilities across diverse histopathology tasks. Building on this progress, we introduce PLUTO-4, our next generation of pathology foundation models that extend the Pathology-Universal Transformer (PLUTO) to frontier scale. We share two complementary Vision Transformer architectures in the PLUTO-4 family: a compact and efficient PLUTO-4S model optimized for multi-scale deployment using a FlexiViT setup with 2D-RoPE embeddings, and a frontier-scale PLUTO-4G model trained with a single patch size to maximize representation capacity and stability. Both models are pretrained using a self-supervised objective derived from DINOv2 on a large multi-institutional corpus containing 551,164 WSIs from 137,144 patients across over 50 institutions, spanning over 60 disease types and over 100 stains. Comprehensive evaluation across public and internal benchmarks demonstrates that PLUTO-4 achieves state-of-the-art performance on tasks requiring varying spatial and biological context, including tile classification, segmentation, and slide-level diagnosis. The compact PLUTO-4S provides high-throughput and robust performance for practical deployment, while PLUTO-4G establishes new performance frontiers across multiple pathology benchmarks, including an 11% improvement in dermatopathology diagnosis. These diverse improvements underscore PLUTO-4's potential to transform real-world applications as a backbone for translational research and diagnostic use cases. △ Less

Submitted 11 November, 2025; v1 submitted 4 November, 2025; originally announced November 2025.

ML-Dev-Bench: Comparative Analysis of AI Agents on ML development workflows

Authors: Harshith Padigela, Chintan Shah, Dinkar Juyal

Abstract: In this report, we present ML-Dev-Bench, a benchmark aimed at testing agentic capabilities on applied Machine Learning development tasks. While existing benchmarks focus on isolated coding tasks or Kaggle-style competitions, ML-Dev-Bench tests agents' ability to handle the full complexity of ML development workflows. The benchmark assesses performance across critical aspects including dataset hand… ▽ More In this report, we present ML-Dev-Bench, a benchmark aimed at testing agentic capabilities on applied Machine Learning development tasks. While existing benchmarks focus on isolated coding tasks or Kaggle-style competitions, ML-Dev-Bench tests agents' ability to handle the full complexity of ML development workflows. The benchmark assesses performance across critical aspects including dataset handling, model training, improving existing models, debugging, and API integration with popular ML tools. We evaluate three agents - ReAct, Openhands, and AIDE - on a diverse set of 30 tasks, providing insights into their strengths and limitations in handling practical ML development challenges. We open source the benchmark for the benefit of the community at \href{https://github.com/ml-dev-bench/ml-dev-bench}{https://github.com/ml-dev-bench/ml-dev-bench}. △ Less

Submitted 19 February, 2025; v1 submitted 2 February, 2025; originally announced February 2025.

Learning biologically relevant features in a pathology foundation model using sparse autoencoders

Authors: Nhat Minh Le, Ciyue Shen, Neel Patel, Chintan Shah, Darpan Sanghavi, Blake Martin, Alfred Eng, Daniel Shenker, Harshith Padigela, Raymond Biju, Syed Ashar Javed, Jennifer Hipp, John Abel, Harsha Pokkalla, Sean Grullon, Dinkar Juyal

Abstract: Pathology plays an important role in disease diagnosis, treatment decision-making and drug development. Previous works on interpretability for machine learning models on pathology images have revolved around methods such as attention value visualization and deriving human-interpretable features from model heatmaps. Mechanistic interpretability is an emerging area of model interpretability that foc… ▽ More Pathology plays an important role in disease diagnosis, treatment decision-making and drug development. Previous works on interpretability for machine learning models on pathology images have revolved around methods such as attention value visualization and deriving human-interpretable features from model heatmaps. Mechanistic interpretability is an emerging area of model interpretability that focuses on reverse-engineering neural networks. Sparse Autoencoders (SAEs) have emerged as a promising direction in terms of extracting monosemantic features from polysemantic model activations. In this work, we trained a Sparse Autoencoder on the embeddings of a pathology pretrained foundation model. We found that Sparse Autoencoder features represent interpretable and monosemantic biological concepts. In particular, individual SAE dimensions showed strong correlations with cell type counts such as plasma cells and lymphocytes. These biological representations were unique to the pathology pretrained model and were not found in a self-supervised model pretrained on natural images. We demonstrated that such biologically-grounded monosemantic representations evolved across the model's depth, and the pathology foundation model eventually gained robustness to non-biological factors such as scanner type. The emergence of biologically relevant SAE features was generalizable to an out-of-domain dataset. Our work paves the way for further exploration around interpretable feature dimensions and their utility for medical and clinical applications. △ Less

Submitted 16 December, 2024; v1 submitted 15 July, 2024; originally announced July 2024.

PLUTO: Pathology-Universal Transformer

Authors: Dinkar Juyal, Harshith Padigela, Chintan Shah, Daniel Shenker, Natalia Harguindeguy, Yi Liu, Blake Martin, Yibo Zhang, Michael Nercessian, Miles Markey, Isaac Finberg, Kelsey Luu, Daniel Borders, Syed Ashar Javed, Emma Krause, Raymond Biju, Aashish Sood, Allen Ma, Jackson Nyman, John Shamshoian, Guillaume Chhor, Darpan Sanghavi, Marc Thibault, Limin Yu, Fedaa Najdawi , et al. (8 additional authors not shown)

Abstract: Pathology is the study of microscopic inspection of tissue, and a pathology diagnosis is often the medical gold standard to diagnose disease. Pathology images provide a unique challenge for computer-vision-based analysis: a single pathology Whole Slide Image (WSI) is gigapixel-sized and often contains hundreds of thousands to millions of objects of interest across multiple resolutions. In this wor… ▽ More Pathology is the study of microscopic inspection of tissue, and a pathology diagnosis is often the medical gold standard to diagnose disease. Pathology images provide a unique challenge for computer-vision-based analysis: a single pathology Whole Slide Image (WSI) is gigapixel-sized and often contains hundreds of thousands to millions of objects of interest across multiple resolutions. In this work, we propose PathoLogy Universal TransfOrmer (PLUTO): a light-weight pathology FM that is pre-trained on a diverse dataset of 195 million image tiles collected from multiple sites and extracts meaningful representations across multiple WSI scales that enable a large variety of downstream pathology tasks. In particular, we design task-specific adaptation heads that utilize PLUTO's output embeddings for tasks which span pathology scales ranging from subcellular to slide-scale, including instance segmentation, tile classification, and slide-level prediction. We compare PLUTO's performance to other state-of-the-art methods on a diverse set of external and internal benchmarks covering multiple biologically relevant tasks, tissue types, resolutions, stains, and scanners. We find that PLUTO matches or outperforms existing task-specific baselines and pathology-specific foundation models, some of which use orders-of-magnitude larger datasets and model sizes when compared to PLUTO. Our findings present a path towards a universal embedding to power pathology image analysis, and motivate further exploration around pathology foundation models in terms of data diversity, architectural improvements, sample efficiency, and practical deployability in real-world applications. △ Less

Submitted 13 May, 2024; originally announced May 2024.

Synthetic DOmain-Targeted Augmentation (S-DOTA) Improves Model Generalization in Digital Pathology

Authors: Sai Chowdary Gullapally, Yibo Zhang, Nitin Kumar Mittal, Deeksha Kartik, Sandhya Srinivasan, Kevin Rose, Daniel Shenker, Dinkar Juyal, Harshith Padigela, Raymond Biju, Victor Minden, Chirag Maheshwari, Marc Thibault, Zvi Goldstein, Luke Novak, Nidhi Chandra, Justin Lee, Aaditya Prakash, Chintan Shah, John Abel, Darren Fahy, Amaro Taylor-Weiner, Anand Sampat

Abstract: Machine learning algorithms have the potential to improve patient outcomes in digital pathology. However, generalization of these tools is currently limited by sensitivity to variations in tissue preparation, staining procedures and scanning equipment that lead to domain shift in digitized slides. To overcome this limitation and improve model generalization, we studied the effectiveness of two Syn… ▽ More Machine learning algorithms have the potential to improve patient outcomes in digital pathology. However, generalization of these tools is currently limited by sensitivity to variations in tissue preparation, staining procedures and scanning equipment that lead to domain shift in digitized slides. To overcome this limitation and improve model generalization, we studied the effectiveness of two Synthetic DOmain-Targeted Augmentation (S-DOTA) methods, namely CycleGAN-enabled Scanner Transform (ST) and targeted Stain Vector Augmentation (SVA), and compared them against the International Color Consortium (ICC) profile-based color calibration (ICC Cal) method and a baseline method using traditional brightness, color and noise augmentations. We evaluated the ability of these techniques to improve model generalization to various tasks and settings: four models, two model types (tissue segmentation and cell classification), two loss functions, six labs, six scanners, and three indications (hepatocellular carcinoma (HCC), nonalcoholic steatohepatitis (NASH), prostate adenocarcinoma). We compared these methods based on the macro-averaged F1 scores on in-distribution (ID) and out-of-distribution (OOD) test sets across multiple domains, and found that S-DOTA methods (i.e., ST and SVA) led to significant improvements over ICC Cal and baseline on OOD data while maintaining comparable performance on ID data. Thus, we demonstrate that S-DOTA may help address generalization due to domain shift in real world applications. △ Less

Submitted 3 May, 2023; originally announced May 2023.

SC-MIL: Supervised Contrastive Multiple Instance Learning for Imbalanced Classification in Pathology

Authors: Dinkar Juyal, Siddhant Shingi, Syed Ashar Javed, Harshith Padigela, Chintan Shah, Anand Sampat, Archit Khosla, John Abel, Amaro Taylor-Weiner

Abstract: Multiple Instance learning (MIL) models have been extensively used in pathology to predict biomarkers and risk-stratify patients from gigapixel-sized images. Machine learning problems in medical imaging often deal with rare diseases, making it important for these models to work in a label-imbalanced setting. In pathology images, there is another level of imbalance, where given a positively labeled… ▽ More Multiple Instance learning (MIL) models have been extensively used in pathology to predict biomarkers and risk-stratify patients from gigapixel-sized images. Machine learning problems in medical imaging often deal with rare diseases, making it important for these models to work in a label-imbalanced setting. In pathology images, there is another level of imbalance, where given a positively labeled Whole Slide Image (WSI), only a fraction of pixels within it contribute to the positive label. This compounds the severity of imbalance and makes imbalanced classification in pathology challenging. Furthermore, these imbalances can occur in out-of-distribution (OOD) datasets when the models are deployed in the real-world. We leverage the idea that decoupling feature and classifier learning can lead to improved decision boundaries for label imbalanced datasets. To this end, we investigate the integration of supervised contrastive learning with multiple instance learning (SC-MIL). Specifically, we propose a joint-training MIL framework in the presence of label imbalance that progressively transitions from learning bag-level representations to optimal classifier learning. We perform experiments with different imbalance settings for two well-studied problems in cancer pathology: subtyping of non-small cell lung cancer and subtyping of renal cell carcinoma. SC-MIL provides large and consistent improvements over other techniques on both in-distribution (ID) and OOD held-out sets across multiple imbalanced settings. △ Less

Submitted 9 September, 2023; v1 submitted 23 March, 2023; originally announced March 2023.

Additive MIL: Intrinsically Interpretable Multiple Instance Learning for Pathology

Authors: Syed Ashar Javed, Dinkar Juyal, Harshith Padigela, Amaro Taylor-Weiner, Limin Yu, Aaditya Prakash

Abstract: Multiple Instance Learning (MIL) has been widely applied in pathology towards solving critical problems such as automating cancer diagnosis and grading, predicting patient prognosis, and therapy response. Deploying these models in a clinical setting requires careful inspection of these black boxes during development and deployment to identify failures and maintain physician trust. In this work, we… ▽ More Multiple Instance Learning (MIL) has been widely applied in pathology towards solving critical problems such as automating cancer diagnosis and grading, predicting patient prognosis, and therapy response. Deploying these models in a clinical setting requires careful inspection of these black boxes during development and deployment to identify failures and maintain physician trust. In this work, we propose a simple formulation of MIL models, which enables interpretability while maintaining similar predictive performance. Our Additive MIL models enable spatial credit assignment such that the contribution of each region in the image can be exactly computed and visualized. We show that our spatial credit assignment coincides with regions used by pathologists during diagnosis and improves upon classical attention heatmaps from attention MIL models. We show that any existing MIL model can be made additive with a simple change in function composition. We also show how these models can debug model failures, identify spurious features, and highlight class-wise regions of interest, enabling their use in high-stakes environments such as clinical decision-making. △ Less

Submitted 16 October, 2022; v1 submitted 3 June, 2022; originally announced June 2022.

Investigating the Successes and Failures of BERT for Passage Re-Ranking

Authors: Harshith Padigela, Hamed Zamani, W. Bruce Croft

Abstract: The bidirectional encoder representations from transformers (BERT) model has recently advanced the state-of-the-art in passage re-ranking. In this paper, we analyze the results produced by a fine-tuned BERT model to better understand the reasons behind such substantial improvements. To this aim, we focus on the MS MARCO passage re-ranking dataset and provide potential reasons for the successes and… ▽ More The bidirectional encoder representations from transformers (BERT) model has recently advanced the state-of-the-art in passage re-ranking. In this paper, we analyze the results produced by a fine-tuned BERT model to better understand the reasons behind such substantial improvements. To this aim, we focus on the MS MARCO passage re-ranking dataset and provide potential reasons for the successes and failures of BERT for retrieval. In more detail, we empirically study a set of hypotheses and provide additional analysis to explain the successful performance of BERT. △ Less

Submitted 5 May, 2019; originally announced May 2019.

A Systematic Classification of Knowledge, Reasoning, and Context within the ARC Dataset

Authors: Michael Boratko, Harshit Padigela, Divyendra Mikkilineni, Pritish Yuvraj, Rajarshi Das, Andrew McCallum, Maria Chang, Achille Fokoue-Nkoutche, Pavan Kapanipathi, Nicholas Mattei, Ryan Musa, Kartik Talamadupula, Michael Witbrock

Abstract: The recent work of Clark et al. introduces the AI2 Reasoning Challenge (ARC) and the associated ARC dataset that partitions open domain, complex science questions into an Easy Set and a Challenge Set. That paper includes an analysis of 100 questions with respect to the types of knowledge and reasoning required to answer them; however, it does not include clear definitions of these types, nor does… ▽ More The recent work of Clark et al. introduces the AI2 Reasoning Challenge (ARC) and the associated ARC dataset that partitions open domain, complex science questions into an Easy Set and a Challenge Set. That paper includes an analysis of 100 questions with respect to the types of knowledge and reasoning required to answer them; however, it does not include clear definitions of these types, nor does it offer information about the quality of the labels. We propose a comprehensive set of definitions of knowledge and reasoning types necessary for answering the questions in the ARC dataset. Using ten annotators and a sophisticated annotation interface, we analyze the distribution of labels across the Challenge Set and statistics related to them. Additionally, we demonstrate that although naive information retrieval methods return sentences that are irrelevant to answering the query, sufficient supporting text is often present in the (ARC) corpus. Evaluating with human-selected relevant sentences improves the performance of a neural machine comprehension model by 42 points. △ Less

Submitted 4 February, 2019; v1 submitted 1 June, 2018; originally announced June 2018.

Comments: Presented at the Machine Reading for Question Answering (MRQA 2018) Workshop at the 55th Annual Meeting of the Association for Computational Linguistics (ACL 2018). 11 pages, 5 tables, 4 figures. Added missing citations in the latest draft