Anna Yeaton

Adalberto Claudio Quiros, Nicolas Coudray, Anna Yeaton et al.

Definitive cancer diagnosis and management depend upon the extraction of information from microscopy images by pathologists. These images contain complex information requiring time-consuming expert human interpretation that is prone to human bias. Supervised deep learning approaches have proven powerful for classification tasks, but they are inherently limited by the cost and quality of annotations used for training these models. To address this limitation of supervised methods, we developed Histomorphological Phenotype Learning (HPL), a fully blue{self-}supervised methodology that requires no expert labels or annotations and operates via the automatic discovery of discriminatory image features in small image tiles. Tiles are grouped into morphologically similar clusters which constitute a library of histomorphological phenotypes, revealing trajectories from benign to malignant tissue via inflammatory and reactive phenotypes. These clusters have distinct features which can be identified using orthogonal methods, linking histologic, molecular and clinical phenotypes. Applied to lung cancer tissues, we show that they align closely with patient survival, with histopathologically recognised tumor types and growth patterns, and with transcriptomic measures of immunophenotype. We then demonstrate that these properties are maintained in a multi-cancer study. These results show the clusters represent recurrent host responses and modes of tumor growth emerging under natural selection. Code, pre-trained models, learned embeddings, and documentation are available to the community at https://github.com/AdalbertoCq/Histomorphological-Phenotype-Learning

Anna Yeaton, Rahul G. Krishnan, Rebecca Mieloszyk et al. · harvard, microsoft-research

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.

Adalberto Claudio Quiros, Nicolas Coudray, Anna Yeaton et al.

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