Anne E. Carpenter

Marzieh Haghighi, Mario C. Cruz, Erin Weisbart et al.

Various strategies for label-scarce object detection have been explored by the computer vision research community. These strategies mainly rely on assumptions that are specific to natural images and not directly applicable to the biological and biomedical vision domains. For example, most semi-supervised learning strategies rely on a small set of labeled data as a confident source of ground truth. In many biological vision applications, however, the ground truth is unknown and indirect information might be available in the form of noisy estimations or orthogonal evidence. In this work, we frame a crucial problem in spatial transcriptomics - decoding barcodes from In-Situ-Sequencing (ISS) images - as a semi-supervised object detection (SSOD) problem. Our proposed framework incorporates additional available sources of information into a semi-supervised learning framework in the form of privileged information. The privileged information is incorporated into the teacher's pseudo-labeling in a teacher-student self-training iteration. Although the available privileged information could be data domain specific, we have introduced a general strategy of pseudo-labeling enhanced by privileged information (PLePI) and exemplified the concept using ISS images, as well on the COCO benchmark using extra evidence provided by CLIP.

John Arevalo, Ellen Su, Anne E Carpenter et al.

Drug-target interaction (DTI) prediction is crucial for identifying new therapeutics and detecting mechanisms of action. While structure-based methods accurately model physical interactions between a drug and its protein target, cell-based assays such as Cell Painting can better capture complex DTI interactions. This paper introduces MOTIVE, a Morphological cOmpound Target Interaction Graph dataset comprising Cell Painting features for 11,000 genes and 3,600 compounds, along with their relationships extracted from seven publicly available databases. We provide random, cold-source (new drugs), and cold-target (new genes) data splits to enable rigorous evaluation under realistic use cases. Our benchmark results show that graph neural networks that use Cell Painting features consistently outperform those that learn from graph structure alone, feature-based models, and topological heuristics. MOTIVE accelerates both graph ML research and drug discovery by promoting the development of more reliable DTI prediction models. MOTIVE resources are available at https://github.com/carpenter-singh-lab/motive.

Gang Liu, Srijit Seal, John Arevalo et al.

Predicting drug efficacy and safety in vivo requires information on biological responses (e.g., cell morphology and gene expression) to small molecule perturbations. However, current molecular representation learning methods do not provide a comprehensive view of cell states under these perturbations and struggle to remove noise, hindering model generalization. We introduce the Information Alignment (InfoAlign) approach to learn molecular representations through the information bottleneck method in cells. We integrate molecules and cellular response data as nodes into a context graph, connecting them with weighted edges based on chemical, biological, and computational criteria. For each molecule in a training batch, InfoAlign optimizes the encoder's latent representation with a minimality objective to discard redundant structural information. A sufficiency objective decodes the representation to align with different feature spaces from the molecule's neighborhood in the context graph. We demonstrate that the proposed sufficiency objective for alignment is tighter than existing encoder-based contrastive methods. Empirically, we validate representations from InfoAlign in two downstream applications: molecular property prediction against up to 27 baseline methods across four datasets, plus zero-shot molecule-morphology matching.

Jane Hung, Deepali Ravel, Stefanie C. P. Lopes et al.

Deep learning based models have had great success in object detection, but the state of the art models have not yet been widely applied to biological image data. We apply for the first time an object detection model previously used on natural images to identify cells and recognize their stages in brightfield microscopy images of malaria-infected blood. Many micro-organisms like malaria parasites are still studied by expert manual inspection and hand counting. This type of object detection task is challenging due to factors like variations in cell shape, density, and color, and uncertainty of some cell classes. In addition, annotated data useful for training is scarce, and the class distribution is inherently highly imbalanced due to the dominance of uninfected red blood cells. We use Faster Region-based Convolutional Neural Network (Faster R-CNN), one of the top performing object detection models in recent years, pre-trained on ImageNet but fine tuned with our data, and compare it to a baseline, which is based on a traditional approach consisting of cell segmentation, extraction of several single-cell features, and classification using random forests. To conduct our initial study, we collect and label a dataset of 1300 fields of view consisting of around 100,000 individual cells. We demonstrate that Faster R-CNN outperforms our baseline and put the results in context of human performance.