Self-supervised learning unveils morphological clusters behind lung cancer types and prognosis

Histopathological images of tumors contain abundant information about how tumors grow and how they interact with their micro-environment. Characterizing and improving our understanding of phenotypes could reveal factors related to tumor progression and their underpinning biological processes, ultimately improving diagnosis and treatment. In recent years, the field of histological deep learning applications has seen great progress, yet most of these applications focus on a supervised approach, relating tissue and associated sample annotations. Supervised approaches have their impact limited by two factors. Firstly, high-quality labels are expensive in time and effort, which makes them not easily scalable. Secondly, these methods focus on predicting annotations from histological images, fundamentally restricting the discovery of new tissue phenotypes. These limitations emphasize the importance of using new methods that can characterize tissue by the features enclosed in the image, without pre-defined annotation or supervision. We present Phenotype Representation Learning (PRL), a methodology to extract histomorphological phenotypes through self-supervised learning and community detection. PRL creates phenotype clusters by identifying tissue patterns that share common morphological and cellular features, allowing to describe whole slide images through compositional representations of cluster contributions. We used this framework to analyze histopathology slides of LUAD and LUSC lung cancer subtypes from TCGA and NYU cohorts. We show that PRL achieves a robust lung subtype prediction providing statistically relevant phenotypes for each lung subtype. We further demonstrate the significance of these phenotypes in lung adenocarcinoma overall and recurrence free survival, relating clusters with patient outcomes, cell types, grown patterns, and omic-based immune signatures.

Hierarchical Optimal Transport for Comparing Histopathology Datasets

Scarcity of labeled histopathology data limits the applicability of deep learning methods to under-profiled cancer types and labels. Transfer learning allows researchers to overcome the limitations of small datasets by pre-training machine learning models on larger datasets similar to the small target dataset. However, similarity between datasets is often determined heuristically. In this paper, we propose a principled notion of distance between histopathology datasets based on a hierarchical generalization of optimal transport distances. Our method does not require any training, is agnostic to model type, and preserves much of the hierarchical structure in histopathology datasets imposed by tiling. We apply our method to H&E stained slides from The Cancer Genome Atlas from six different cancer types. We show that our method outperforms a baseline distance in a cancer-type prediction task. Our results also show that our optimal transport distance predicts difficulty of transferability in a tumor vs.normal prediction setting.

Adversarial learning of cancer tissue representations

Deep learning based analysis of histopathology images shows promise in advancing the understanding of tumor progression, tumor micro-environment, and their underpinning biological processes. So far, these approaches have focused on extracting information associated with annotations. In this work, we ask how much information can be learned from the tissue architecture itself. We present an adversarial learning model to extract feature representations of cancer tissue, without the need for manual annotations. We show that these representations are able to identify a variety of morphological characteristics across three cancer types: Breast, colon, and lung. This is supported by 1) the separation of morphologic characteristics in the latent space; 2) the ability to classify tissue type with logistic regression using latent representations, with an AUC of 0.97 and 85% accuracy, comparable to supervised deep models; 3) the ability to predict the presence of tumor in Whole Slide Images (WSIs) using multiple instance learning (MIL), achieving an AUC of 0.98 and 94% accuracy. Our results show that our model captures distinct phenotypic characteristics of real tissue samples, paving the way for further understanding of tumor progression and tumor micro-environment, and ultimately refining histopathological classification for diagnosis and treatment. The code and pretrained models are available at: https://github.com/AdalbertoCq/Adversarial-learning-of-cancer-tissue-representations