Amy Xiang Wang, Zakhar Shumaylov, Peter Zaika, Ferdia Sherry, Carola-Bibiane Schönlieb
Physics-informed neural operators (PINOs) have emerged as powerful tools for learning solution operators of partial differential equations (PDEs). Recent research has demonstrated that incorporating Lie point symmetry information can significantly enhance the training efficiency of PINOs, primarily through techniques like data, architecture, and loss augmentation. In this work, we focus on the latter, highlighting that point symmetries oftentimes result in no training signal, limiting their effectiveness in many problems. To address this, we propose a novel loss augmentation strategy that leverages evolutionary representatives of point symmetries, a specific class of generalized symmetries of the underlying PDE. These generalized symmetries provide a richer set of generators compared to standard symmetries, leading to a more informative training signal. We demonstrate that leveraging evolutionary representatives enhances the performance of neural operators, resulting in improved data efficiency and accuracy during training.
Chenyu Wang, Masatoshi Uehara, Yichun He, Amy Wang, Tommaso Biancalani, Avantika Lal, Tommi Jaakkola, Sergey Levine, Hanchen Wang, Aviv Regev
Recent studies have demonstrated the strong empirical performance of diffusion models on discrete sequences across domains from natural language to biological sequence generation. For example, in the protein inverse folding task, conditional diffusion models have achieved impressive results in generating natural-like sequences that fold back into the original structure. However, practical design tasks often require not only modeling a conditional distribution but also optimizing specific task objectives. For instance, we may prefer protein sequences with high stability. To address this, we consider the scenario where we have pre-trained discrete diffusion models that can generate natural-like sequences, as well as reward models that map sequences to task objectives. We then formulate the reward maximization problem within discrete diffusion models, analogous to reinforcement learning (RL), while minimizing the KL divergence against pretrained diffusion models to preserve naturalness. To solve this RL problem, we propose a novel algorithm, DRAKES, that enables direct backpropagation of rewards through entire trajectories generated by diffusion models, by making the originally non-differentiable trajectories differentiable using the Gumbel-Softmax trick. Our theoretical analysis indicates that our approach can generate sequences that are both natural-like and yield high rewards. While similar tasks have been recently explored in diffusion models for continuous domains, our work addresses unique algorithmic and theoretical challenges specific to discrete diffusion models, which arise from their foundation in continuous-time Markov chains rather than Brownian motion. Finally, we demonstrate the effectiveness of DRAKES in generating DNA and protein sequences that optimize enhancer activity and protein stability, respectively, important tasks for gene therapies and protein-based therapeutics.
Daniel McDuff, Mike Schaekermann, Tao Tu, Anil Palepu, Amy Wang, Jake Garrison, Karan Singhal, Yash Sharma, Shekoofeh Azizi, Kavita Kulkarni, Le Hou, Yong Cheng, Yun Liu, S Sara Mahdavi, Sushant Prakash, Anupam Pathak, Christopher Semturs, Shwetak Patel, Dale R Webster, Ewa Dominowska, Juraj Gottweis, Joelle Barral, Katherine Chou, Greg S Corrado, Yossi Matias, Jake Sunshine, Alan Karthikesalingam, Vivek Natarajan
An accurate differential diagnosis (DDx) is a cornerstone of medical care, often reached through an iterative process of interpretation that combines clinical history, physical examination, investigations and procedures. Interactive interfaces powered by Large Language Models (LLMs) present new opportunities to both assist and automate aspects of this process. In this study, we introduce an LLM optimized for diagnostic reasoning, and evaluate its ability to generate a DDx alone or as an aid to clinicians. 20 clinicians evaluated 302 challenging, real-world medical cases sourced from the New England Journal of Medicine (NEJM) case reports. Each case report was read by two clinicians, who were randomized to one of two assistive conditions: either assistance from search engines and standard medical resources, or LLM assistance in addition to these tools. All clinicians provided a baseline, unassisted DDx prior to using the respective assistive tools. Our LLM for DDx exhibited standalone performance that exceeded that of unassisted clinicians (top-10 accuracy 59.1% vs 33.6%, [p = 0.04]). Comparing the two assisted study arms, the DDx quality score was higher for clinicians assisted by our LLM (top-10 accuracy 51.7%) compared to clinicians without its assistance (36.1%) (McNemar's Test: 45.7, p < 0.01) and clinicians with search (44.4%) (4.75, p = 0.03). Further, clinicians assisted by our LLM arrived at more comprehensive differential lists than those without its assistance. Our study suggests that our LLM for DDx has potential to improve clinicians' diagnostic reasoning and accuracy in challenging cases, meriting further real-world evaluation for its ability to empower physicians and widen patients' access to specialist-level expertise.
Karan Singhal, Tao Tu, Juraj Gottweis, Rory Sayres, Ellery Wulczyn, Le Hou, Kevin Clark, Stephen Pfohl, Heather Cole-Lewis, Darlene Neal, Mike Schaekermann, Amy Wang, Mohamed Amin, Sami Lachgar, Philip Mansfield, Sushant Prakash, Bradley Green, Ewa Dominowska, Blaise Aguera y Arcas, Nenad Tomasev, Yun Liu, Renee Wong, Christopher Semturs, S. Sara Mahdavi, Joelle Barral, Dale Webster, Greg S. Corrado, Yossi Matias, Shekoofeh Azizi, Alan Karthikesalingam, Vivek Natarajan
Recent artificial intelligence (AI) systems have reached milestones in "grand challenges" ranging from Go to protein-folding. The capability to retrieve medical knowledge, reason over it, and answer medical questions comparably to physicians has long been viewed as one such grand challenge. Large language models (LLMs) have catalyzed significant progress in medical question answering; Med-PaLM was the first model to exceed a "passing" score in US Medical Licensing Examination (USMLE) style questions with a score of 67.2% on the MedQA dataset. However, this and other prior work suggested significant room for improvement, especially when models' answers were compared to clinicians' answers. Here we present Med-PaLM 2, which bridges these gaps by leveraging a combination of base LLM improvements (PaLM 2), medical domain finetuning, and prompting strategies including a novel ensemble refinement approach. Med-PaLM 2 scored up to 86.5% on the MedQA dataset, improving upon Med-PaLM by over 19% and setting a new state-of-the-art. We also observed performance approaching or exceeding state-of-the-art across MedMCQA, PubMedQA, and MMLU clinical topics datasets. We performed detailed human evaluations on long-form questions along multiple axes relevant to clinical applications. In pairwise comparative ranking of 1066 consumer medical questions, physicians preferred Med-PaLM 2 answers to those produced by physicians on eight of nine axes pertaining to clinical utility (p < 0.001). We also observed significant improvements compared to Med-PaLM on every evaluation axis (p < 0.001) on newly introduced datasets of 240 long-form "adversarial" questions to probe LLM limitations. While further studies are necessary to validate the efficacy of these models in real-world settings, these results highlight rapid progress towards physician-level performance in medical question answering.
Tao Tu, Anil Palepu, Mike Schaekermann, Khaled Saab, Jan Freyberg, Ryutaro Tanno, Amy Wang, Brenna Li, Mohamed Amin, Nenad Tomasev, Shekoofeh Azizi, Karan Singhal, Yong Cheng, Le Hou, Albert Webson, Kavita Kulkarni, S Sara Mahdavi, Christopher Semturs, Juraj Gottweis, Joelle Barral, Katherine Chou, Greg S Corrado, Yossi Matias, Alan Karthikesalingam, Vivek Natarajan
At the heart of medicine lies the physician-patient dialogue, where skillful history-taking paves the way for accurate diagnosis, effective management, and enduring trust. Artificial Intelligence (AI) systems capable of diagnostic dialogue could increase accessibility, consistency, and quality of care. However, approximating clinicians' expertise is an outstanding grand challenge. Here, we introduce AMIE (Articulate Medical Intelligence Explorer), a Large Language Model (LLM) based AI system optimized for diagnostic dialogue. AMIE uses a novel self-play based simulated environment with automated feedback mechanisms for scaling learning across diverse disease conditions, specialties, and contexts. We designed a framework for evaluating clinically-meaningful axes of performance including history-taking, diagnostic accuracy, management reasoning, communication skills, and empathy. We compared AMIE's performance to that of primary care physicians (PCPs) in a randomized, double-blind crossover study of text-based consultations with validated patient actors in the style of an Objective Structured Clinical Examination (OSCE). The study included 149 case scenarios from clinical providers in Canada, the UK, and India, 20 PCPs for comparison with AMIE, and evaluations by specialist physicians and patient actors. AMIE demonstrated greater diagnostic accuracy and superior performance on 28 of 32 axes according to specialist physicians and 24 of 26 axes according to patient actors. Our research has several limitations and should be interpreted with appropriate caution. Clinicians were limited to unfamiliar synchronous text-chat which permits large-scale LLM-patient interactions but is not representative of usual clinical practice. While further research is required before AMIE could be translated to real-world settings, the results represent a milestone towards conversational diagnostic AI.
Aya Abdelsalam Ismail, Tuomas Oikarinen, Amy Wang, Julius Adebayo, Samuel Stanton, Taylor Joren, Joseph Kleinhenz, Allen Goodman, Héctor Corrada Bravo, Kyunghyun Cho, Nathan C. Frey
We introduce Concept Bottleneck Protein Language Models (CB-pLM), a generative masked language model with a layer where each neuron corresponds to an interpretable concept. Our architecture offers three key benefits: i) Control: We can intervene on concept values to precisely control the properties of generated proteins, achieving a 3 times larger change in desired concept values compared to baselines. ii) Interpretability: A linear mapping between concept values and predicted tokens allows transparent analysis of the model's decision-making process. iii) Debugging: This transparency facilitates easy debugging of trained models. Our models achieve pre-training perplexity and downstream task performance comparable to traditional masked protein language models, demonstrating that interpretability does not compromise performance. While adaptable to any language model, we focus on masked protein language models due to their importance in drug discovery and the ability to validate our model's capabilities through real-world experiments and expert knowledge. We scale our CB-pLM from 24 million to 3 billion parameters, making them the largest Concept Bottleneck Models trained and the first capable of generative language modeling.
Peter Brodeur, Jacob M. Koshy, Anil Palepu, Khaled Saab, Ava Homiar, Roma Ruparel, Charles Wu, Ryutaro Tanno, Joseph Xu, Amy Wang, David Stutz, Wei-Hung Weng, Hannah M. Ferrera, David Barrett, Lindsey Crowley, Jihyeon Lee, Spencer E. Rittner, Ellery Wulczyn, Selena K. Zhang, Elahe Vedadi, Christine G. Kohn, Kavita Kulkarni, Vinay Kadiyala, Sara Mahdavi, Wendy Du, Jessica M. Williams, David Feinbloom, Renee Wong, Tao Tu, Petar Sirkovic, Alessio Orlandi, Christopher Semturs, Yun Liu, Juraj Gottweis, Dale R. Webster, Joëlle Barral, Katherine Chou, Pushmeet Kohli, Avinatan Hassidim, Yossi Matias, James Manyika, Rob Fields, Jonathan X. Li, Marc L. Cohen, Vivek Natarajan, Mike Schaekermann, Alan Karthikesalingam, Adam Rodman
Large language model (LLM)-based AI systems have shown promise for patient-facing diagnostic and management conversations in simulated settings. Translating these systems into clinical practice requires assessment in real-world workflows with rigorous safety oversight. We report a prospective, single-arm feasibility study of an LLM-based conversational AI, the Articulate Medical Intelligence Explorer (AMIE), conducting clinical history taking and presentation of potential diagnoses for patients to discuss with their provider at urgent care appointments at a leading academic medical center. 100 adult patients completed an AMIE text-chat interaction up to 5 days before their appointment. We sought to assess the conversational safety and quality, patient and clinician experience, and clinical reasoning capabilities compared to primary care providers (PCPs). Human safety supervisors monitored all patient-AMIE interactions in real time and did not need to intervene to stop any consultations based on pre-defined criteria. Patients reported high satisfaction and their attitudes towards AI improved after interacting with AMIE (p < 0.001). PCPs found AMIE's output useful with a positive impact on preparedness. AMIE's differential diagnosis (DDx) included the final diagnosis, per chart review 8 weeks post-encounter, in 90% of cases, with 75% top-3 accuracy. Blinded assessment of AMIE and PCP DDx and management (Mx) plans suggested similar overall DDx and Mx plan quality, without significant differences for DDx (p = 0.6) and appropriateness and safety of Mx (p = 0.1 and 1.0, respectively). PCPs outperformed AMIE in the practicality (p = 0.003) and cost effectiveness (p = 0.004) of Mx. While further research is needed, this study demonstrates the initial feasibility, safety, and user acceptance of conversational AI in a real-world setting, representing crucial steps towards clinical translation.
LearnLM Team, Abhinit Modi, Aditya Srikanth Veerubhotla, Aliya Rysbek, Andrea Huber, Brett Wiltshire, Brian Veprek, Daniel Gillick, Daniel Kasenberg, Derek Ahmed, Irina Jurenka, James Cohan, Jennifer She, Julia Wilkowski, Kaiz Alarakyia, Kevin R. McKee, Lisa Wang, Markus Kunesch, Mike Schaekermann, Miruna Pîslar, Nikhil Joshi, Parsa Mahmoudieh, Paul Jhun, Sara Wiltberger, Shakir Mohamed, Shashank Agarwal, Shubham Milind Phal, Sun Jae Lee, Theofilos Strinopoulos, Wei-Jen Ko, Amy Wang, Ankit Anand, Avishkar Bhoopchand, Dan Wild, Divya Pandya, Filip Bar, Garth Graham, Holger Winnemoeller, Mahvish Nagda, Prateek Kolhar, Renee Schneider, Shaojian Zhu, Stephanie Chan, Steve Yadlowsky, Viknesh Sounderajah, Yannis Assael
Today's generative AI systems are tuned to present information by default, rather than engage users in service of learning as a human tutor would. To address the wide range of potential education use cases for these systems, we reframe the challenge of injecting pedagogical behavior as one of \textit{pedagogical instruction following}, where training and evaluation examples include system-level instructions describing the specific pedagogy attributes present or desired in subsequent model turns. This framing avoids committing our models to any particular definition of pedagogy, and instead allows teachers or developers to specify desired model behavior. It also clears a path to improving Gemini models for learning -- by enabling the addition of our pedagogical data to post-training mixtures -- alongside their rapidly expanding set of capabilities. Both represent important changes from our initial tech report. We show how training with pedagogical instruction following produces a LearnLM model (available on Google AI Studio) that experts substantially prefer across a diverse set of learning scenarios, with average preference strengths of +31\% over GPT-4o, +11\% over Claude 3.5 Sonnet, and +13\% over the Gemini 1.5 Pro model on which LearnLM was based.
LearnLM Team, Google, :, Alicia Martín, Amir Globerson, Amy Wang, Anirudh Shekhawat, Anna Iurchenko, Anisha Choudhury, Avinatan Hassidim, Ayça Çakmakli, Ayelet Shasha Evron, Charlie Yang, Courtney Heldreth, Diana Akrong, Gal Elidan, Hairong Mu, Ian Li, Ido Cohen, Katherine Chou, Komal Singh, Lev Borovoi, Lidan Hackmon, Lior Belinsky, Michael Fink, Niv Efron, Preeti Singh, Rena Levitt, Shashank Agarwal, Shay Sharon, Tracey Lee-Joe, Xiaohong Hao, Yael Gold-Zamir, Yael Haramaty, Yishay Mor, Yoav Bar Sinai, Yossi Matias
Textbooks are a cornerstone of education, but they have a fundamental limitation: they are a one-size-fits-all medium. Any new material or alternative representation requires arduous human effort, so that textbooks cannot be adapted in a scalable manner. We present an approach for transforming and augmenting textbooks using generative AI, adding layers of multiple representations and personalization while maintaining content integrity and quality. We refer to the system built with this approach as Learn Your Way. We report pedagogical evaluations of the different transformations and augmentations, and present the results of a a randomized control trial, highlighting the advantages of learning with Learn Your Way over regular textbook usage.
Rory Sayres, Yuexing Hao, Abbi Ward, Amy Wang, Beverly Freeman, Serena Zhan, Diego Ardila, Jimmy Li, I-Ching Lee, Anna Iurchenko, Siyi Kou, Kartikeya Badola, Jimmy Hu, Bhawesh Kumar, Keith Johnson, Supriya Vijay, Justin Krogue, Avinatan Hassidim, Yossi Matias, Dale R. Webster, Sunny Virmani, Yun Liu, Quang Duong, Mike Schaekermann
Navigating health questions can be daunting in the modern information landscape. Large language models (LLMs) may provide tailored, accessible information, but also risk being inaccurate, biased or misleading. We present insights from 4 mixed-methods studies (total N=163), examining how people interact with LLMs for their own health questions. Qualitative studies revealed the importance of context-seeking in conversational AIs to elicit specific details a person may not volunteer or know to share. Context-seeking by LLMs was valued by participants, even if it meant deferring an answer for several turns. Incorporating these insights, we developed a "Wayfinding AI" to proactively solicit context. In a randomized, blinded study, participants rated the Wayfinding AI as more helpful, relevant, and tailored to their concerns compared to a baseline AI. These results demonstrate the strong impact of proactive context-seeking on conversational dynamics, and suggest design patterns for conversational AI to help navigate health topics.