Major depressive disorder (MDD) is a critical cause of morbidity and disability with an economic cost hundreds billions dollars each year, necessitating more effective treatment strategies novel approaches to translational research. A notable barrier in addressing this public health threat involves reliable identification the disorder, as many affected individuals remain undiagnosed or misdiagnosed. An objective blood-based diagnostic test using transcript levels panel markers would provide...

Computational models are most impactful when they explain and characterize biological phenomena that non-intuitive, unexpected, or difficult to study experimentally. Countless equation-based have been built for these purposes, but we yet realize the extent which rules-based offer an intuitive framework encourages computational experimental collaboration. We develop ARCADE, a multi-scale agent-based model interrogate emergent behavior of heterogeneous cell agents within dynamic...

Chimeric antigen receptor (CAR) T-cell therapy shows promise for treating liquid cancers and increasingly solid tumors as well. While potential design strategies exist to address translational challenges, including the lack of unique tumor antigens presence an immunosuppressive microenvironment, testing all possible choices in vitro vivo is prohibitively expensive, time consuming, laborious. To this gap, we extended modeling framework ARCADE (Agent-based Representation Cells And Dynamic...

Thermotropic liquid crystals are typically thought of as requiring a rigid core and flexible side‐chains to exhibit crystallinity, but precedent does exist for retaining crystalline nature without these in highly conjugated, para‐substituted aromatic structures, albeit at relatively high temperatures (> 300 °C). Hence, this work aims establish molecular design criteria promoting crystallinity heteroaromatic, fully core‐only calamitic sufficiently low phase transition temperatures. The...

The dynamic bending and twisting of actin drives numerous cellular processes. To compare how different spatial scales in models capture these dynamics, we developed two filaments: one at monomer-scale using ReaDDy fiber-scale Cytosim. Simulating filament compression across a range velocities, found divergence between the monomer- simulations; notably, simulations more effectively captured supertwist, characteristic helical structure, but higher computational cost. Such comparisons can aid...

Cells do not exist in isolation; they continuously act within and react to their environment. And this environment is static; it adapts responds cells. Here, we investigate how vascular structure function impact emergent cell population behavior using an agent-based model (ABM). Our ABM enables researchers "mix match" agents, subcellular modules, microenvironment components ranging from simple nutrient sources complex, realistic architectures that accurately capture hemodynamics. We use...

High throughput screening by fluorescence activated cell sorting (FACS) is a common task in protein engineering and directed evolution. It can also be rate-limiting step if high false positive or negative rates necessitate multiple rounds of enrichment. Current FACS software requires the user to define gates intuition practically limited two dimensions. In cases when enrichment are required, cannot forecast effort required.We have developed CellSort, support vector machine (SVM) algorithm...

Network inference algorithms aim to uncover key regulatory interactions governing cellular decision-making, disease progression and therapeutic interventions. Having an accurate blueprint of this regulation is essential for understanding controlling cell behavior. However, the utility impact these approaches are limited because ways in which various factors shape outcomes remain largely unknown.We identify systematically evaluate determinants performance-including network properties,...

Computational models enable scientists to understand observed dynamics, uncover rules underlying behaviors, predict experimental outcomes, and generate new hypotheses. There are countless modeling approaches that can be used characterize biological systems, further multiplied when accounting for the variety of model design choices. Many studies focus on impact parameters output performance; fewer investigate choices insight. Here we demonstrate why should deliberate intentional in context...

The promiscuity of G-protein-coupled receptors (GPCRs) has broad implications in disease, pharmacology and biosensing. Promiscuity is a particularly crucial consideration for protein engineering, where the ability to modulate model essential developing desirable proteins. Here, we present methodologies (i) modifying GPCR using directed evolution (ii) predicting receptor response identifying important peptide features quantitative structure-activity relationship models grouping-exhaustive...

Abstract Motivation Emergent biological dynamics derive from the evolution of lower-level spatial and temporal processes. A long-standing challenge for scientists engineers is identifying simple low-level rules that give rise to complex higher-level dynamics. High-resolution data acquisition enables this identification has evolved at a rapid pace both experimental computational approaches. Simultaneously harnessing resolution managing expense emerging technologies—e.g. live cell imaging,...

Abstract Motivation Emergent biological dynamics derive from the evolution of lower-level spatial and temporal processes. A long-standing challenge for scientists engineers is identifying simple low-level rules that give rise to complex higher-level dynamics. High-resolution data acquisition enables this identification has evolved at a rapid pace both experimental computational approaches. Simultaneously harnessing resolution managing expense emerging technologies—e.g. live cell imaging,...

Abstract Iterating between data-driven research and generative computational models is a powerful approach for emulating biological systems, testing hypotheses, gaining deeper understanding of these systems. We developed hybrid agent-based model (ABM) that integrates Cellular Potts Model (CPM) designed to investigate cell shape colony dynamics in human induced pluripotent stem (hiPS cell) colonies. This aimed first mimic then explore the observed real-world hiPS cultures. Initial outputs...

Abstract Chimeric antigen receptor (CAR) T-cell therapy shows promise for treating liquid cancers and increasingly solid tumors as well. While potential design strategies exist to address translational challenges, including the lack of unique tumor antigens presence an immunosuppressive microenvironment, testing all possible choices in vitro vivo is prohibitively expensive, time consuming, laborious. To this gap, we extended modeling framework ARCADE (Agent-based Representation Cells And...