Dimensional reduction of phenotypes from 53 000 mouse models reveals a diverse landscape of gene function.

Animal models have long been used to study gene function and the impact of genetic mutations on phenotype. Through the research efforts of thousands of research groups, systematic curation of published literature and high-throughput phenotyping screens, the collective body of knowledge for the mouse now covers the majority of protein-coding genes. We here collected data for over 53 000 mouse models with mutations in over 15 000 genomic markers and characterized by more than 254 000 annotations using more than 9000 distinct ontology terms. We investigated dimensional reduction and embedding techniques as means to facilitate access to this diverse and high-dimensional information. Our analyses provide the first visual maps of the landscape of mouse phenotypic diversity. We also summarize some of the difficulties in producing and interpreting embeddings of sparse phenotypic data. In particular, we show that data preprocessing, filtering and encoding have as much impact on the final embeddings as the process of dimensional reduction. Nonetheless, techniques developed in the context of dimensional reduction create opportunities for explorative analysis of this large pool of public data, including for searching for mouse models suited to study human diseases.
Availability and Implementation: Source code for analysis scripts is available on GitHub at https://github.com/tkonopka/mouse-embeddings. The data underlying this article are available in Zenodo at https://doi.org/10.5281/zenodo.4916171.
Contact: t.konopka@qmul.ac.uk.
Supplementary Information: Supplementary data are available at Bioinformatics Advances online.
(© The Author(s) 2021. Published by Oxford University Press.)