Chang, H.-T. | bioRxiv Science

bioRxiv2024

The Taiwan Precision Medicine Initiative: A Cohort for Large-Scale Studies

The Taiwan Precision Medicine Initiative (TPMI), a project initiated by the Academia Sinica in collaboration with 16 major medical centers around Taiwan, has recruited 565,390 participants who consented to provide DNA samples for genetic profiling and grant access to their electronic medical records (EMR) for studies to develop precision medicine. Access to the EMR is both retrospective and prospective, allowing researchers to conduct prospective studies over time. Genetic profiling is done with population-optimized SNP arrays for the Han Chinese populations that enable genetic analyses such as genome-wide association, phenome-wide association, and polygenic risk score studies to evaluate common disease risk and pharmacogenetic response. Furthermore, the TPMI participants agree to be contacted for future research opportunities related to their genetic risks and receive personalized genetic risk profiles with health management recommendations. TPMI has established the TPMI Data Access Platform (TDAP), a central database and analysis platform that both safeguards the security of the data and facilitates academic research. The TPMI is the largest non-European cohort that merges genetic profiles with EMR in the world. With a cohort that can be followed over time, it can be utilized to validate genetic risk prediction models, conduct clinical trials to show the efficacy of risk-based health management, and optimize health policies based on genetic risks. In this report, we describe the TPMI study design, the population and genetic characteristics of the TPMI cohort, and the power it provides to conduct crucial studies in developing precision medicine on a population and personal level. As Han Chinese represent almost 20% of the worlds population, the results of TPMI studies will benefit >1.4 billion people around the world and serve as a model for developing population-based precision medicine.

genetics↗

bioRxiv2020

Phenotype Spectrum reflects Synergies among the Cell Architecture over Stages of the Cell Cycle

The heterogeneity of cell phenotypes remains a barrier in progressing cell research and a challenge in conquering cancer-related drug resistance. Cell morphology, the most direct property of cell phenotype, evolves along the progression of the cell cycle; meanwhile, cell motility, the dynamic property of cell phenotype, also alters over the cell cycle. However, a quantifiable research understanding the strict relationship between the cell cycle and cell migration is missing. Herein, we separately elucidate the correspondence of single NIH 3T3 fibroblast migratory behaviors with the G1, S, and G2 phases of the cell cycle, an underlying property of proliferation. The results show that synergies among the highly spatiotemporal arrangements of signals in Rho GTPases and cyclin-dependent kinase inhibitors, p21Cip1, and p27Kip1 coordinates proliferation and migration. Taken together, we explain the synergies among these processes through providing an interactive molecular mechanism between the cell cycle and cell migration and demonstrate that both cell morphology and the dynamic subcellular behavior are homogenous within each stage of the cell cycle phases, posing potential implications in countering drug resistance.

cell biology↗