Tx-LLM: A Large Language Model for Therapeutics

Developing therapeutics is a lengthy and expensive process that requires the satisfaction of many different criteria, and AI models capable of expediting the process would be invaluable. However, the majority of current AI approaches address only a narrowly defined set of tasks, often circumscribed within a particular domain. To bridge this gap, we introduce Tx-LLM, a generalist large language model (LLM) fine-tuned from PaLM-2 which encodes knowledge about diverse therapeutic modalities. Tx-LLM is trained using a collection of 709 datasets that target 66 tasks spanning various stages of the drug discovery pipeline. Using a single set of weights, Tx-LLM simultaneously processes a wide variety of chemical or biological entities(small molecules, proteins, nucleic acids, cell lines, diseases) interleaved with free-text, allowing it to predict a broad range of associated properties, achieving competitive with state-of-the-art (SOTA) performance on 43 out of 66 tasks and exceeding SOTA on 22. Among these, Tx-LLM is particularly powerful and exceeds best-in-class performance on average for tasks combining molecular SMILES representations with text such as cell line names or disease names, likely due to context learned during pretraining. We observe evidence of positive transfer between tasks with diverse drug types (e.g.,tasks involving small molecules and tasks involving proteins), and we study the impact of model size, domain finetuning, and prompting strategies on performance. We believe Tx-LLM represents an important step towards LLMs encoding biochemical knowledge and could have a future role as an end-to-end tool across the drug discovery development pipeline.

Semantic Loss Functions for Neuro-Symbolic Structured Prediction

Structured output prediction problems are ubiquitous in machine learning. The prominent approach leverages neural networks as powerful feature extractors, otherwise assuming the independence of the outputs. These outputs, however, jointly encode an object, e.g. a path in a graph, and are therefore related through the structure underlying the output space. We discuss the semantic loss, which injects knowledge about such structure, defined symbolically, into training by minimizing the network's violation of such dependencies, steering the network towards predicting distributions satisfying the underlying structure. At the same time, it is agnostic to the arrangement of the symbols, and depends only on the semantics expressed thereby, while also enabling efficient end-to-end training and inference. We also discuss key improvements and applications of the semantic loss. One limitations of the semantic loss is that it does not exploit the association of every data point with certain features certifying its membership in a target class. We should therefore prefer minimum-entropy distributions over valid structures, which we obtain by additionally minimizing the neuro-symbolic entropy. We empirically demonstrate the benefits of this more refined formulation. Moreover, the semantic loss is designed to be modular and can be combined with both discriminative and generative neural models. This is illustrated by integrating it into generative adversarial networks, yielding constrained adversarial networks, a novel class of deep generative models able to efficiently synthesize complex objects obeying the structure of the underlying domain.

Advancing Multimodal Medical Capabilities of Gemini

Many clinical tasks require an understanding of specialized data, such as medical images and genomics, which is not typically found in general-purpose large multimodal models. Building upon Gemini's multimodal models, we develop several models within the new Med-Gemini family that inherit core capabilities of Gemini and are optimized for medical use via fine-tuning with 2D and 3D radiology, histopathology, ophthalmology, dermatology and genomic data. Med-Gemini-2D sets a new standard for AI-based chest X-ray (CXR) report generation based on expert evaluation, exceeding previous best results across two separate datasets by an absolute margin of 1% and 12%, where 57% and 96% of AI reports on normal cases, and 43% and 65% on abnormal cases, are evaluated as "equivalent or better" than the original radiologists' reports. We demonstrate the first ever large multimodal model-based report generation for 3D computed tomography (CT) volumes using Med-Gemini-3D, with 53% of AI reports considered clinically acceptable, although additional research is needed to meet expert radiologist reporting quality. Beyond report generation, Med-Gemini-2D surpasses the previous best performance in CXR visual question answering (VQA) and performs well in CXR classification and radiology VQA, exceeding SoTA or baselines on 17 of 20 tasks. In histopathology, ophthalmology, and dermatology image classification, Med-Gemini-2D surpasses baselines across 18 out of 20 tasks and approaches task-specific model performance. Beyond imaging, Med-Gemini-Polygenic outperforms the standard linear polygenic risk score-based approach for disease risk prediction and generalizes to genetically correlated diseases for which it has never been trained. Although further development and evaluation are necessary in the safety-critical medical domain, our results highlight the potential of Med-Gemini across a wide range of medical tasks.

Security and Privacy Product Inclusion

In this paper, we explore the challenges of ensuring security and privacy for users from diverse demographic backgrounds. We propose a threat modeling approach to identify potential risks and countermeasures for product inclusion in security and privacy. We discuss various factors that can affect a user's ability to achieve a high level of security and privacy, including low-income demographics, poor connectivity, shared device usage, ML fairness, etc. We present results from a global security and privacy user experience survey and discuss the implications for product developers. Our work highlights the need for a more inclusive approach to security and privacy and provides a framework for researchers and practitioners to consider when designing products and services for a diverse range of users.

Speeding up and reducing memory usage for scientific machine learning via mixed precision

Scientific machine learning (SciML) has emerged as a versatile approach to address complex computational science and engineering problems. Within this field, physics-informed neural networks (PINNs) and deep operator networks (DeepONets) stand out as the leading techniques for solving partial differential equations by incorporating both physical equations and experimental data. However, training PINNs and DeepONets requires significant computational resources, including long computational times and large amounts of memory. In search of computational efficiency, training neural networks using half precision (float16) rather than the conventional single (float32) or double (float64) precision has gained substantial interest, given the inherent benefits of reduced computational time and memory consumed. However, we find that float16 cannot be applied to SciML methods, because of gradient divergence at the start of training, weight updates going to zero, and the inability to converge to a local minima. To overcome these limitations, we explore mixed precision, which is an approach that combines the float16 and float32 numerical formats to reduce memory usage and increase computational speed. Our experiments showcase that mixed precision training not only substantially decreases training times and memory demands but also maintains model accuracy. We also reinforce our empirical observations with a theoretical analysis. The research has broad implications for SciML in various computational applications.

Multi-Rate VAE: Train Once, Get the Full Rate-Distortion Curve

Variational autoencoders (VAEs) are powerful tools for learning latent representations of data used in a wide range of applications. In practice, VAEs usually require multiple training rounds to choose the amount of information the latent variable should retain. This trade-off between the reconstruction error (distortion) and the KL divergence (rate) is typically parameterized by a hyperparameter $\beta$. In this paper, we introduce Multi-Rate VAE (MR-VAE), a computationally efficient framework for learning optimal parameters corresponding to various $\beta$ in a single training run. The key idea is to explicitly formulate a response function that maps $\beta$ to the optimal parameters using hypernetworks. MR-VAEs construct a compact response hypernetwork where the pre-activations are conditionally gated based on $\beta$. We justify the proposed architecture by analyzing linear VAEs and showing that it can represent response functions exactly for linear VAEs. With the learned hypernetwork, MR-VAEs can construct the rate-distortion curve without additional training and can be deployed with significantly less hyperparameter tuning. Empirically, our approach is competitive and often exceeds the performance of multiple $\beta$-VAEs training with minimal computation and memory overheads.

Neuro-Symbolic Entropy Regularization

In structured prediction, the goal is to jointly predict many output variables that together encode a structured object -- a path in a graph, an entity-relation triple, or an ordering of objects. Such a large output space makes learning hard and requires vast amounts of labeled data. Different approaches leverage alternate sources of supervision. One approach -- entropy regularization -- posits that decision boundaries should lie in low-probability regions. It extracts supervision from unlabeled examples, but remains agnostic to the structure of the output space. Conversely, neuro-symbolic approaches exploit the knowledge that not every prediction corresponds to a valid structure in the output space. Yet, they does not further restrict the learned output distribution. This paper introduces a framework that unifies both approaches. We propose a loss, neuro-symbolic entropy regularization, that encourages the model to confidently predict a valid object. It is obtained by restricting entropy regularization to the distribution over only valid structures. This loss is efficiently computed when the output constraint is expressed as a tractable logic circuit. Moreover, it seamlessly integrates with other neuro-symbolic losses that eliminate invalid predictions. We demonstrate the efficacy of our approach on a series of semi-supervised and fully-supervised structured-prediction experiments, where we find that it leads to models whose predictions are more accurate and more likely to be valid.

Probabilistic Sufficient Explanations

Understanding the behavior of learned classifiers is an important task, and various black-box explanations, logical reasoning approaches, and model-specific methods have been proposed. In this paper, we introduce probabilistic sufficient explanations, which formulate explaining an instance of classification as choosing the "simplest" subset of features such that only observing those features is "sufficient" to explain the classification. That is, sufficient to give us strong probabilistic guarantees that the model will behave similarly when all features are observed under the data distribution. In addition, we leverage tractable probabilistic reasoning tools such as probabilistic circuits and expected predictions to design a scalable algorithm for finding the desired explanations while keeping the guarantees intact. Our experiments demonstrate the effectiveness of our algorithm in finding sufficient explanations, and showcase its advantages compared to Anchors and logical explanations.

Leveraging Unlabeled Data for Entity-Relation Extraction through Probabilistic Constraint Satisfaction

We study the problem of entity-relation extraction in the presence of symbolic domain knowledge. Such knowledge takes the form of an ontology defining relations and their permissible arguments. Previous approaches set out to integrate such knowledge in their learning approaches either through self-training, or through approximations that lose the precise meaning of the logical expressions. By contrast, our approach employs semantic loss which captures the precise meaning of a logical sentence through maintaining a probability distribution over all possible states, and guiding the model to solutions which minimize any constraint violations. With a focus on low-data regimes, we show that semantic loss outperforms the baselines by a wide margin.

Stochastic Optimization of Sorting Networks via Continuous Relaxations

Sorting input objects is an important step in many machine learning pipelines. However, the sorting operator is non-differentiable with respect to its inputs, which prohibits end-to-end gradient-based optimization. In this work, we propose NeuralSort, a general-purpose continuous relaxation of the output of the sorting operator from permutation matrices to the set of unimodal row-stochastic matrices, where every row sums to one and has a distinct arg max. This relaxation permits straight-through optimization of any computational graph involve a sorting operation. Further, we use this relaxation to enable gradient-based stochastic optimization over the combinatorially large space of permutations by deriving a reparameterized gradient estimator for the Plackett-Luce family of distributions over permutations. We demonstrate the usefulness of our framework on three tasks that require learning semantic orderings of high-dimensional objects, including a fully differentiable, parameterized extension of the k-nearest neighbors algorithm.