Systematic exploration of cell morphological phenotypes associated with a transcriptomic query

Cell morphological phenotypes, including shape, size, intensity, and texture of cellular compartments have been shown to change in response to perturbation with small molecule compounds. Image-based cell profiling or cell morphological profiling has been used to associate changes of cell morphological features with alterations in cellular function and to infer molecular mechanisms of action. Recently, the Library of Integrated Network-based Cellular Signatures (LINCS) Project has measured gene expression and performed image-based cell profiling on cell lines treated with 9515 unique compounds. These data provide an opportunity to study the interdependence between transcription and cell morphology. Previous methods to investigate cell phenotypes have focused on targeting candidate genes as components of known pathways, RNAi morphological profiling, and cataloging morphological defects; however, these methods do not provide an explicit model to link transcriptomic changes with corresponding alterations in morphology. To address this, we propose a cell morphology enrichment analysis to assess the association between transcriptomic alterations and changes in cell morphology. Additionally, for a new transcriptomic query, our approach can be used to predict associated changes in cellular morphology. We demonstrate the utility of our method by applying it to cell morphological changes in a human bone osteosarcoma cell line.