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Novel Morphological Phenotypes Discovery in High-Content Screens Using Underused Features

Cell-based high-content screening (HCS) is a powerful high-throughput technology for studying cellular processes through the analysis of complex cellular morphology. A typical large-scale HCS screen can generate many novel morphological phenotypes. It is challenging to identify novel phenotypes due to the huge volume of data and the lack of domain knowledge. This paper presents a new strategy that discovers novel phenotypes using underused image features, which are defined as those not fully utilized by the existing phenotypes. Our approach was successfully applied to a data set generated in a genetic HCS of Drosophila BG-2 cells to discover novel phenotypes and make interesting predictions.