Interpretable neural architecture search and transfer learning for understanding CRISPR-Cas9 off-target enzymatic reactions.

Finely tuned enzymatic pathways control cellular processes, and their dysregulation can lead to disease. Developing predictive and interpretable models for these pathways is challenging because of the complexity of the pathways and of the cellular and genomic contexts. Here we introduce Elektrum, a deep learning framework that addresses these challenges with data-driven and biophysically interpretable models for determining the kinetics of biochemical systems.

Interpretable neural architecture search and transfer learning for understanding CRISPR/Cas9 off-target enzymatic reactions.

Finely-tuned enzymatic pathways control cellular processes, and their dysregulation can lead to disease. Creating predictive and interpretable models for these pathways is challenging because of the complexity of the pathways and of the cellular and genomic contexts. Here we introduce , a deep learning framework which addresses these challenges with data-driven and biophysically interpretable models for determining the kinetics of biochemical systems.

Comparison of explicit and mean-field models of cytoskeletal filaments with crosslinking motors.

In cells, cytoskeletal filament networks are responsible for cell movement, growth, and division. Filaments in the cytoskeleton are driven and organized by crosslinking molecular motors. In reconstituted cytoskeletal systems, motor activity is responsible for far-from-equilibrium phenomena such as active stress, self-organized flow, and spontaneous nematic defect generation.

Mechanisms of chromosome biorientation and bipolar spindle assembly analyzed by computational modeling.

The essential functions required for mitotic spindle assembly and chromosome biorientation and segregation are not fully understood, despite extensive study. To illuminate the combinations of ingredients most important to align and segregate chromosomes and simultaneously assemble a bipolar spindle, we developed a computational model of fission-yeast mitosis. Robust chromosome biorientation requires progressive restriction of attachment geometry, destabilization of misaligned attachments, and attachment force dependence.

Theory of Cytoskeletal Reorganization during Cross-Linker-Mediated Mitotic Spindle Assembly.

Cells grow, move, and respond to outside stimuli by large-scale cytoskeletal reorganization. A prototypical example of cytoskeletal remodeling is mitotic spindle assembly, during which microtubules nucleate, undergo dynamic instability, bundle, and organize into a bipolar spindle. Key mechanisms of this process include regulated filament polymerization, cross-linking, and motor-protein activity.