Macaque genotype-phenotype resources: A prismatic portal into human biology and disease

Macaque genotype-phenotype resources: A prismatic portal into human biology and disease Non-human primates serve as indispensable models in biomedical research due to their high degree of genetic, physiological, and behavioral similarity to humans (Yao, 2022).Macaques are among the most widely used species in studies of drug efficacy, disease mechanisms, and neural function (National Academies of Sciences, Engineering, and Medicine et al., 2023).However, recent increases in global demand, compounded by public health emergencies such as the COVID-19 pandemic, have resulted in widespread shortages and escalating costs (Grimm, 2023).A more persistent constraint is the limited availability of macaques with well-documented genotypic and phenotypic profiles, which restricts experimental reproducibility and reduces the reliability of research results (Bimber et al., 2019).To address this dual quantitative and qualitative crisis, a macaque biobank integrating large-scale phenotypic and multi-omics datasets is imperative to support standardized, reproducible research (Figure 1).Such a resource enables precise stratification and selection of individuals based on defined traits or genotypes relevant to specific drug responses, disease susceptibility, or other experimental variables, thereby minimizing inter-individual variability and enhancing experimental reproducibility and translational relevance.It also facilitates the discovery of naturally occurring macaque models harboring clinically relevant variants or spontaneous pathological phenotypes, reducing reliance on labor-intensive, ethically constrained artificial engineering of disease models.Following the establishment of the Big Monkey Facility (Yao, 2022), the Macaque Biobank project was initiated to generate a comprehensive dataset from a large cohort of originally wild-caught and bred individuals.The first phase has yielded important findings regarding the genetic basis of phenotypic variation and enabled the identification of spontaneous models using a reverse-genomics approach (Zhang et al., 2025).However, phenotypic data collection in macaques presents distinct methodological challenges that differ fundamentally from those encountered in human biobanking.A key constraint arises from the inability of macaques to cooperate voluntarily with examination procedures, necessitating physical restraint or chemical sedation even for basic measurements.These interventions inevitably induce stress responses that significantly disrupt baseline physiological states, leading to alterations in heart rate, blood pressure, and