An official website of the United States government
Biomedical knowledge graphs (KGs) encode rich, structured information critical for drug discovery tasks, but extracting meaningful insights from large-scale KGs remains challenging due to their complex structure. Existing biomedical subgraph retrieval methods are tailored for graph neural networks (GNNs), limiting compatibility with other paradigms, including large language models (LLMs). We introduce K-Paths, a model-agnostic retrieval framework that extracts structured, diverse, and biologically meaningful multi-hop paths from dense biomedical KGs. These paths enable prediction of unobserved drug-drug and drug-disease interactions, including those involving entities not seen during training, thus supporting inductive reasoning. K-Paths is training-free and employs a diversity-aware adaptation of Yen's algorithm to extract the K shortest loopless paths between entities in a query, prioritizing biologically relevant and relationally diverse connections. These paths serve as concise, interpretable reasoning chains that can be directly integrated with LLMs or GNNs to improve generalization, accuracy, and enable explainable inference. Experiments on benchmark datasets show that K-Paths improves zero-shot reasoning across state-of-the-art LLMs. For instance, Tx-Gemma 27B improves by 19.8 and 4.0 F1 points on interaction severity prediction and drug repurposing tasks, respectively. Llama 70B achieves gains of 8.5 and 6.2 points on the same tasks. K-Paths also boosts the training efficiency of EmerGNN, a state-of-the-art GNN, by reducing the KG size by 90% while maintaining predictive performance. Beyond efficiency, K-Paths bridges the gap between KGs and LLMs, enabling scalable and explainable LLM-augmented scientific discovery. We release our code and the retrieved paths as a benchmark for inductive reasoning.
more »
« less
This content will become publicly available on December 1, 2025
CancerGPT for few shot drug pair synergy prediction using large pretrained language models
Abstract Large language models (LLMs) have been shown to have significant potential in few-shot learning across various fields, even with minimal training data. However, their ability to generalize to unseen tasks in more complex fields, such as biology and medicine has yet to be fully evaluated. LLMs can offer a promising alternative approach for biological inference, particularly in cases where structured data and sample size are limited, by extracting prior knowledge from text corpora. Here we report our proposed few-shot learning approach, which uses LLMs to predict the synergy of drug pairs in rare tissues that lack structured data and features. Our experiments, which involved seven rare tissues from different cancer types, demonstrate that the LLM-based prediction model achieves significant accuracy with very few or zero samples. Our proposed model, the CancerGPT (with ~ 124M parameters), is comparable to the larger fine-tuned GPT-3 model (with ~ 175B parameters). Our research contributes to tackling drug pair synergy prediction in rare tissues with limited data, and also advancing the use of LLMs for biological and medical inference tasks.
more »
« less
- Award ID(s):
- 2505865
- PAR ID:
- 10631103
- Publisher / Repository:
- npj Digital Medicine
- Date Published:
- Journal Name:
- npj Digital Medicine
- Volume:
- 7
- Issue:
- 1
- ISSN:
- 2398-6352
- Format(s):
- Medium: X
- Sponsoring Org:
- National Science Foundation
More Like this
-
-
Advances in large language models (LLMs) have empowered a variety of applications. However, there is still a significant gap in research when it comes to understanding and enhancing the capabilities of LLMs in the field of mental health. In this work, we present a comprehensive evaluation of multiple LLMs on various mental health prediction tasks via online text data, including Alpaca, Alpaca-LoRA, FLAN-T5, GPT-3.5, and GPT-4. We conduct a broad range of experiments, covering zero-shot prompting, few-shot prompting, and instruction fine-tuning. The results indicate a promising yet limited performance of LLMs with zero-shot and few-shot prompt designs for mental health tasks. More importantly, our experiments show that instruction finetuning can significantly boost the performance of LLMs for all tasks simultaneously. Our best-finetuned models, Mental-Alpaca and Mental-FLAN-T5, outperform the best prompt design of GPT-3.5 (25 and 15 times bigger) by 10.9% on balanced accuracy and the best of GPT-4 (250 and 150 times bigger) by 4.8%. They further perform on par with the state-of-the-art task-specific language model. We also conduct an exploratory case study on LLMs' capability on mental health reasoning tasks, illustrating the promising capability of certain models such as GPT-4. We summarize our findings into a set of action guidelines for potential methods to enhance LLMs' capability for mental health tasks. Meanwhile, we also emphasize the important limitations before achieving deployability in real-world mental health settings, such as known racial and gender bias. We highlight the important ethical risks accompanying this line of research.more » « less
-
null (Ed.)The problem of learning to generalize on unseen classes during the training step, also known as few-shot classification, has attracted considerable attention. Initialization based methods, such as the gradient-based model agnostic meta-learning (MAML) [1], tackle the few-shot learning problem by “learning to fine-tune”. The goal of these approaches is to learn proper model initialization so that the classifiers for new classes can be learned from a few labeled examples with a small number of gradient update steps. Few shot meta-learning is well-known with its fast-adapted capability and accuracy generalization onto unseen tasks [2]. Learning fairly with unbiased outcomes is another significant hallmark of human intelligence, which is rarely touched in few-shot meta-learning. In this work, we propose a novel Primal-Dual Fair Meta-learning framework, namely PDFM, which learns to train fair machine learning models using only a few examples based on data from related tasks. The key idea is to learn a good initialization of a fair model’s primal and dual parameters so that it can adapt to a new fair learning task via a few gradient update steps. Instead of manually tuning the dual parameters as hyperparameters via a grid search, PDFM optimizes the initialization of the primal and dual parameters jointly for fair meta-learning via a subgradient primal-dual approach. We further instantiate an example of bias controlling using decision boundary covariance (DBC) [3] as the fairness constraint for each task, and demonstrate the versatility of our proposed approach by applying it to classification on a variety of three real-world datasets. Our experiments show substantial improvements over the best prior work for this setting.more » « less
-
Representation Learning), a novel multimodal meta-learning framework for few-shot learning in heterogeneous systems, designed for science and engineering problems where entities share a common underlying forward model but exhibit heterogeneity due to entity-specific characteristics. TAM-RL leverages an amortized training process with a modulation network and a base network to learn task-specific modulation parameters, enabling efficient adaptation to new tasks with limited data. We evaluate TAM-RL on two real-world environmental datasets: Gross Primary Product (GPP) prediction and streamflow forecasting, demonstrating significant improvements over existing meta-learning methods. On the FLUXNET dataset, TAM-RL improves RMSE by 18.9% over MMAML with just one month of few-shot data, while for streamflow prediction, it achieves an 8.21% improvement with one year of data. Synthetic data experiments further validate TAM-RL’s superior performance in heterogeneous task distributions, outperforming the baselines in the most heterogeneous setting. Notably, TAM-RL offers substantial computational efficiency, with at least 3x faster training times compared to gradient-based meta-learning approaches while being much simpler to train due to reduced complexity. Ablation studies highlight the importance of pretraining and adaptation mechanisms in TAM-RL’s performance. Keywords: Representation Learning, meta-learning, few-shot learning, environmental applications, time-series. DOI:10.1137/1.9781611978520.2more » « less
-
Abstract Designing for manufacturing poses significant challenges in part due to the computation bottleneck of Computer-Aided Manufacturing (CAM) simulations. Although deep learning as an alternative offers fast inference, its performance is dependently bounded by the need for abundant training data. Representation learning, particularly through pre-training, offers promise for few-shot learning, aiding in manufacturability tasks where data can be limited. This work introduces VIRL, a Volume-Informed Representation Learning approach to pre-train a 3D geometric encoder. The pretrained model is evaluated across four manufacturability indicators obtained from CAM simulations: subtractive machining (SM) time, additive manufacturing (AM) time, residual von Mises stress, and blade collisions during Laser Power Bed Fusion process. Across all case studies, the model pre-trained by VIRL shows substantial enhancements in generalizability, as measured by R2 regression results, with improved performance on limited data and superior predictive accuracy with larger datasets. Regarding deployment strategy, case-specific phenomenon exists where finetuning VIRL-pretrained models adversely affects AM tasks with limited data but benefits SM time prediction. Moreover, the efficacy of Low-rank adaptation (LoRA), which balances between probing and finetuning, is explored. LoRA shows stable performance akin to probing with limited data, while achieving a higher upper bound than probing as data size increases, without the computational costs of finetuning. Furthermore, static normalization of manufacturing indicators consistently performs well across tasks, while dynamic normalization enhances performance when a reliable task dependent input is available.more » « less
