Clinical significance of spatiotemporal transcriptional bursting and control.

The rapid development of technologies provides the potential to perform real-time visualization of transcriptional bursting patterns, superenhancer formation and sensitivity to perturbation, and interactions between enhancers, promoters, and regulators during the burst. The transcriptional bursting-induced fluctuation can modify cell capacities, cell-cell communications, cell responses to microenvironmental changes, and forms of cell death. A large number of clinical and translational studies describe the existence of heterogeneity among cells, tissues, and organs but mechanism-based understanding of how and why the heterogeneity exists and how it is formed.

Off-target genome editing: A new discipline of gene science and a new class of medicine.

With an increasing growth of genome editing, off-target effects such as non-specific genetic modifications resulting from the designed process of genome editing become a new discipline of gene science and new class medicine. The degree of short-term and long-term side effects and toxicity or dynamics of the primary and secondary off-target genome editing varies with the application of different methodologies of gene editing and measuring, readouts of genetic modifications, or comparison reference. Measurements of dynamic off-target effects caused directly or indirectly by genome editing are critical in clinical application of gene editing.

Systems heterogeneity: An integrative way to understand cancer heterogeneity.

The concept of systems heterogeneity was firstly coined and explained in the Special Issue, as a new alternative to understand the importance and complexity of heterogeneity in cancer. Systems heterogeneity can offer a full image of heterogeneity at multi-dimensional functions and multi-omics by integrating gene or protein expression, epigenetics, sequencing, phosphorylation, transcription, pathway, or interaction. The Special Issue starts with the roles of epigenetics in the initiation and development of cancer heterogeneity through the interaction between permanent genetic mutations and dynamic epigenetic alterations.

Prediction of dynamical drug sensitivity and resistance by module network rewiring-analysis based on transcriptional profiling.

Revealing functional reorganization or module rewiring between modules at network levels during drug treatment is important to systematically understand therapies and drug responses. The present article proposed a novel model of module network rewiring to characterize functional reorganization of a complex biological system, and described a new framework named as module network rewiring-analysis (MNR) for systematically studying dynamical drug sensitivity and resistance during drug treatment. MNR was used to investigate functional reorganization or rewiring on the module network, rather than molecular network or individual molecules.