Tracing dynamic biological processes during phase transition

Phase transition widely exists in the biological world, such as transformation of cell cycle phases, cell differentiation stages, disease development, and so on. Such a nonlinear phenomenon is considered as the conversion of a biological system from one phenotype/state to another. Studies on the molecular mechanisms of biological phase transition have attracted much attention, in particular, on different genotypes (or expression variations) in a specific phase, but with less of focus on cascade changes of genes' functions (or system state) during the phase shift or transition process. However, it is a fundamental but important mission to trace the temporal characteristics of a biological system during a specific phase transition process, which can offer clues for understanding dynamic behaviors of living organisms.

By overcoming the hurdles of traditional time segmentation and temporal biclustering methods, a causal process model (CPM) in the present work is proposed to study the biological phase transition in a systematic manner, i.e. first, we make gene-specific segmentation on time-course expression data by developing a new boundary gene estimation scheme, and then infer functional cascade dynamics by constructing a temporal block network. After the computational validation on synthetic data, CPM was used to analyze the well-known Yeast cell cycle data. It was found that the dynamics of the boundary genes are periodic and consistent with the phases of the cell cycle, and the temporal block network indeed demonstrates a meaningful cascade structure of the enriched biological functions. In addition, we further studied protein modules based on the temporal block network, which reflect temporal features in different cycles.

All of these results demonstrate that CPM is effective and efficient comparing to traditional methods, and is able to elucidate essential regulatory mechanism of a biological system even with complicated nonlinear phase transitions.