PCIM: Learning Pixel Attributions via Pixel-wise Channel Isolation Mixing in High Content Imaging

Deep Neural Networks (DNNs) have shown remarkable success in various computer vision tasks. However, their black-box nature often leads to difficulty in interpreting their decisions, creating an unfilled need for methods to explain the decisions, and ultimately forming a barrier to their wide acceptance especially in biomedical applications. This work introduces a novel method, Pixel-wise Channel Isolation Mixing (PCIM), to calculate pixel attribution maps, highlighting the image parts most crucial for a classification decision but without the need to extract internal network states or gradients. Unlike existing methods, PCIM treats each pixel as a distinct input channel and trains a blending layer to mix these pixels, reflecting specific classifications. This unique approach allows the generation of pixel attribution maps for each image, but agnostic to the choice of the underlying classification network. Benchmark testing on three application relevant, diverse high content Imaging datasets show state-of-the-art performance, particularly for model fidelity and localization ability in both, fluorescence and bright field High Content Imaging. PCIM contributes as a unique and effective method for creating pixel-level attribution maps from arbitrary DNNs, enabling interpretability and trust.

Learning Channel Importance for High Content Imaging with Interpretable Deep Input Channel Mixing

Uncovering novel drug candidates for treating complex diseases remain one of the most challenging tasks in early discovery research. To tackle this challenge, biopharma research established a standardized high content imaging protocol that tags different cellular compartments per image channel. In order to judge the experimental outcome, the scientist requires knowledge about the channel importance with respect to a certain phenotype for decoding the underlying biology. In contrast to traditional image analysis approaches, such experiments are nowadays preferably analyzed by deep learning based approaches which, however, lack crucial information about the channel importance. To overcome this limitation, we present a novel approach which utilizes multi-spectral information of high content images to interpret a certain aspect of cellular biology. To this end, we base our method on image blending concepts with alpha compositing for an arbitrary number of channels. More specifically, we introduce DCMIX, a lightweight, scaleable and end-to-end trainable mixing layer which enables interpretable predictions in high content imaging while retaining the benefits of deep learning based methods. We employ an extensive set of experiments on both MNIST and RXRX1 datasets, demonstrating that DCMIX learns the biologically relevant channel importance without scarifying prediction performance.