The International Mouse Phenotyping Consortium (IMPC) is a $500 million world-wide partnership of research institutions focused on understanding the function of every gene in the mouse genome by looking at the effect on the mice when that gene is removed (knocked out; KO). Almost every gene found in one species so far has been found in a closely related form in the other. Of the approximately 4,000 genes that have been studied, less than 10 are found in one species but not in the other. Thus, by studying mice KOs we hope we can infer function of the same human gene. The IMPC identified immunophenotyping by flow cytometry (FCM) as one of ~30 phenotyping assays to understand each gene’s function. This cutting-edge genomics research is generating the largest ever FCM dataset. The full quantitative potential of the IMPC FCM effort can only be realized with mechanisms to effectively analyze, interpret and share the data. We addressed these shortcomings by developing algorithms tools for (1) Customizing data analysis pipelines for high-throughput processing of IMPC FCM data; (2) Identifying the genes with and specific cell populations responsible for immune system functioning; (3) Extending a public FCM database to include IMPC data.
By the end of the project, they put together a manuscript submitting to Cell (IF 32), where they quantitatively monitored and assessed the multi-organ immune responses of 400 individual genes to multiple challenges from thousands of age-matched, co-located KO mice. They demonstrated a major fraction of the genome contributes to an individual’s immune system, found the profound sex effect on the immune system functional genes, emphasizing the value of stratifying human subjects by the combination of immune monitoring and genotype and sex. They leveraged their findings to a successful GC 2015 BCB project, and formed a spin-off company (Cytapex Bioinformatics Inc) providing flow cytometry data analysis services worldwide to researchers, clinicians, contract research organizations and large pharmaceutical organizations.