Transcriptomics-guided Slide Representation Learning in Computational Pathology

TL;DR

This paper introduces Tangle, a multimodal pre-training method that leverages gene expression profiles to improve slide embedding learning in computational pathology, demonstrating superior performance in few-shot and retrieval tasks.

Contribution

The paper presents Tangle, a novel multimodal pre-training strategy that aligns histology images with gene expression data to enhance slide representation learning.

Findings

Tangle outperforms supervised and SSL baselines in few-shot learning.

Tangle achieves better prototype-based classification results.

Tangle significantly improves slide retrieval performance.

Abstract

Self-supervised learning (SSL) has been successful in building patch embeddings of small histology images (e.g., 224x224 pixels), but scaling these models to learn slide embeddings from the entirety of giga-pixel whole-slide images (WSIs) remains challenging. Here, we leverage complementary information from gene expression profiles to guide slide representation learning using multimodal pre-training. Expression profiles constitute highly detailed molecular descriptions of a tissue that we hypothesize offer a strong task-agnostic training signal for learning slide embeddings. Our slide and expression (S+E) pre-training strategy, called Tangle, employs modality-specific encoders, the outputs of which are aligned via contrastive learning. Tangle was pre-trained on samples from three different organs: liver (n=6,597 S+E pairs), breast (n=1,020), and lung (n=1,012) from two different species (Homo sapiens and Rattus norvegicus). Across three independent test datasets consisting of 1,265 breast WSIs, 1,946 lung WSIs, and 4,584 liver WSIs, Tangle shows significantly better few-shot performance compared to supervised and SSL baselines. When assessed using prototype-based classification and slide retrieval, Tangle also shows a substantial performance improvement over all baselines. Code available at https://github.com/mahmoodlab/TANGLE.