Validation of microphysiological systems for interpreting patient heterogeneity requires robust reproducibility analytics and experimental metadata
Mark T. Miedel, Mahboubeh Varmazyad, Mengying Xia, Maria Mori Brooks, Dillon Gavlock, Celeste E. Reese, Jaideep Behari, Alejandro Soto–Gutiérrez, Albert Gough, D. Lansing Taylor, Mark E. Schurdak
Abstract
Multi-cell-type, 3D microphysiological systems (MPS) that recapitulate normal organ/organ system functions and the progression of diseases are being applied in drug discovery and development programs to enable precision medicine. A critical step for this application is to demonstrate the reproducibility of the MPS and its ability to identify biologic/clinical heterogeneity from experimental variability, which requires capturing detailed metadata associated with MPS studies as well as a strong analytical approach for assessing reproducibility. Detailed metadata ensure that identical study parameters are being compared when evaluating reproducibility. We have developed the Pittsburgh reproducibility protocol (PReP), which uses a set of common statistical metrics, the coefficient of variation (CV), ANOVA, and intraclass correlation coefficient (ICC), in a pipeline as a standard approach to evaluate the intra- and interstudy reproducibility of MPS performance. The PReP can be employed to identify biological/clinical heterogeneity relevant to precision medicine.