Cancer is the second leading cause of death in the world. Diagnosing cancer early on can save many lives. Pathologists have to look at tissue microarray (TMA) images manually to identify tumors, which can be time-consuming, inconsistent and subjective. Existing automatic algorithms either have not achieved the accuracy level of a pathologist or require substantial human involvements. A major challenge is that TMA images with different shapes, sizes, and locations can have the same score. Learning staining patterns in TMA images requires a huge number of images, which are severely limited due to privacy and regulation concerns in medical organizations. TMA images from different cancer types may share certain common characteristics, but combining them directly harms the accuracy due to heterogeneity in their staining patterns. Transfer learning is an emerging learning paradigm that allows borrowing strength from similar problems. However, existing approaches typically require a large sample from similar learning problems, while TMA images of different cancer types are often available in small sample size and further existing algorithms are limited to transfer learning from one similar problem. We propose a new transfer learning algorithm that could learn from multiple related problems, where each problem has a small sample and can have a substantially different distribution from the original one. The proposed algorithm has made it possible to break the critical accuracy barrier (the 75% accuracy level of pathologists), with a reported accuracy of 75.9% on breast cancer TMA images from the Stanford Tissue Microarray Database. It is supported by recent developments in transfer learning theory and empirical evidence in clustering technology. This will allow pathologists to confidently adopt automatic algorithms in recognizing tumors consistently with a higher accuracy in real time.

Tissue microarray (TMA) images have emerged as an important high-throughput tool for cancer study and the validation of biomarkers. Efforts have been dedicated to further improve the accuracy of TACOMA, a cutting-edge automatic scoring algorithm for TMA images. One major advance is due to deepTacoma, an algorithm that incorporates suitable deep representations of a group nature. Inspired by the recent advance in semi-supervised learning and deep learning, we propose mfTacoma to learn alternative deep representations in the context of TMA image scoring. In particular, mfTacoma learns the low-dimensional manifolds, a common latent structure in high dimensional data. Deep representation learning and manifold learning typically requires large data. By encoding deep representation of the manifolds as regularizing features, mfTacoma effectively leverages the manifold information that is potentially crude due to small data. Our experiments show that deep features by manifolds outperforms two alternatives -- deep features by linear manifolds with principal component analysis or by leveraging the group property.

Tissue microarray (TMA) images have been used increasingly often in cancer studies and the validation of biomarkers. TACOMA---a cutting-edge automatic scoring algorithm for TMA images---is comparable to pathologists in terms of accuracy and repeatability. Here we consider how this algorithm may be further improved. Inspired by the recent success of deep learning, we propose to incorporate representations learnable through computation. We explore representations of a group nature through unsupervised learning, e.g., hierarchical clustering and recursive space partition. Information carried by clustering or spatial partitioning may be more concrete than the labels when the data are heterogeneous, or could help when the labels are noisy. The use of such information could be viewed as regularization in model fitting. It is motivated by major challenges in TMA image scoring---heterogeneity and label noise, and the cluster assumption in semi-supervised learning. Using this information on TMA images of breast cancer, we have reduced the error rate of TACOMA by about 6%. Further simulations on synthetic data provide insights on when such representations would likely help. Although we focus on TMAs, learnable representations of this type are expected to be applicable in other settings.