From Genes to Insights

A TRANSFORMATIVE DECADE OF PHENOTYPING AT THE CZECH CENTRE FOR PHENOGENOMICS

Over the past decade, the phenotyping at the Czech Centre for Phenogenomics (CCP) has undergone a profound transformation, mirroring the broader evolution of functional genomics. What began as the development of standardized phenotyping pipelines has evolved into a robust scientific ecosystem that bridges gene discovery, disease mechanisms, and preclinical translation.

In the early years, a significant portion of our effort was dedicated to establishing the foundational technological platform. We optimized individual phenotyping assays, standardized workflows, enforced rigorous quality control, documented metadata meticulously, and ensured comprehensive training for our team to operate within a strictly reproducible environment. Even at this stage, our ambitions extended beyond routine service. By 2016, while refining many pipelines, the team embarked on its first systematic phenotyping of International Mouse Phenotyping Consortium (IMPC) cohorts, formally joining the global initiative to assign biological functions to mammalian genes. From the outset, our emphasis has been not only on throughput but also on depth, interpretability, and biological context.

As the years progressed, the complexity and scale of our phenotyping expanded significantly. We added secondary and tertiary assays, incorporated new expert domains, and gradually integrated hypothesis-driven projects. Specialized units were developed to address the need for studying both baseline physiology and pathological states. We established dedicated platforms for cancer models and patient-derived xenografts, thereby enabling direct interactions with clinically relevant disease biology. During the COVID-19 crisis, we swiftly responded to urgent societal needs by building capacity for infectious disease models under BSL-3 conditions. This expansion required both new infrastructure and a fundamental broadening of expertise and mindset.

Today, our phenotyping efforts have achieved a scale and maturity that would have been hard to envision at the outset. We have phenotyped over 600 genes to date, maintaining an impressive pace of 60 to 80 new genes each year. Our work encompasses more than 1,000 physiological parameters, showcasing the extensive analytical capabilities of the CCP. Phenotyping is no longer viewed as a linear downstream process following model generation; rather, it has become a central intellectual activity that shapes experimental design, guides interpretation, and frames biological questions.

Increasingly, the experience gained through large-scale phenotyping has been leveraged for translational and preclinical research. We have learned to navigate from complex, multidimensional phenotypic data to identify actionable disease mechanisms and potential therapeutic targets. A significant milestone was reached in 2025 when we conducted our first large-scale gene therapy safety study under full Good Laboratory Practice (GLP) conditions. The findings from this study directly supported the initiation of a clinical trial with our first patients, marking a pivotal shift from experimental modeling to tangible medical impact.

Throughout this decade-long journey, a consistent philosophy has guided the team’s development. Phenotyping has never been regarded as a mere technical service or an isolated module within a larger organization. Instead, it has been nurtured as a creative scientific environment driven by curiosity, critical thinking, and close collaboration. Our team members routinely transition between standardized pipelines, technology development, data exploration across the vast IMPC landscape, and participation in ambitious preclinical projects. This continuity of expertise allows experimental results to be interpreted within a coherent scientific framework, rather than as disjointed datasets. It is precisely this integration, encompassing routine phenotyping, methodological innovation, disease modeling, and preclinical testing, that has empowered the CCP to evolve from a functional genomics platform into a genuine engine of translational discovery.