Multilevel Artificial Neural Network Training for Spatially Correlated Learning

Multigrid modeling algorithms are a technique used to accelerate relaxation models running on a hierarchy of similar graphlike structures. We introduce and demonstrate a new method for training neural networks which uses multilevel methods. Using an objective function derived from a graph-distance metric, we perform orthogonally-constrained optimization to find optimal prolongation and restriction maps between graphs. We compare and contrast several methods for performing this numerical optimization, and additionally present some new theoretical results on upper bounds of this type of objective function. Once calculated, these optimal maps between graphs form the core of Multiscale Artificial Neural Network (MsANN) training, a new procedure we present which simultaneously trains a hierarchy of neural network models of varying spatial resolution. Parameter information is passed between members of this hierarchy according to standard coarsening and refinement schedules from the multiscale modelling literature. In our machine learning experiments, these models are able to learn faster than default training, achieving a comparable level of error in an order of magnitude fewer training examples.Comment: Manuscript (24 pages) and Supplementary Material (4 pages). Updated January 2019 to reflect new formulation of MsANN structure and new training procedur

Prospects for Declarative Mathematical Modeling of Complex Biological Systems

Declarative modeling uses symbolic expressions to represent models. With such expressions one can formalize high-level mathematical computations on models that would be difficult or impossible to perform directly on a lower-level simulation program, in a general-purpose programming language. Examples of such computations on models include model analysis, relatively general-purpose model-reduction maps, and the initial phases of model implementation, all of which should preserve or approximate the mathematical semantics of a complex biological model. The potential advantages are particularly relevant in the case of developmental modeling, wherein complex spatial structures exhibit dynamics at molecular, cellular, and organogenic levels to relate genotype to multicellular phenotype. Multiscale modeling can benefit from both the expressive power of declarative modeling languages and the application of model reduction methods to link models across scale. Based on previous work, here we define declarative modeling of complex biological systems by defining the operator algebra semantics of an increasingly powerful series of declarative modeling languages including reaction-like dynamics of parameterized and extended objects; we define semantics-preserving implementation and semantics-approximating model reduction transformations; and we outline a "meta-hierarchy" for organizing declarative models and the mathematical methods that can fruitfully manipulate them

Tracking Cell Signals in Fluorescent Images

In this paper we present the techniques for tracking cell signal in GFP (Green Fluorescent Protein) images of growing cell colonies. We use such tracking for both data extraction and dynamic modeling of intracellular processes. The techniques are based on optimization of energy functions, which simultaneously determines cell correspondences, while estimating the mapping functions. In addition to spatial mappings such as affine and Thin-Plate Spline mapping, the cell growth and cell division histories must be estimated as well. Different levels of joint optimization are discussed. The most unusual tracking feature addressed in this paper is the possibility of one-to-two correspondences caused by cell division. A novel extended softassign algorithm for solutions of one-to-many correspondences is detailed in this paper. The techniques are demonstrated on three sets of data: growing bacillus Subtillus and e-coli colonies and a developing plant shoot apical meristem. The techniques are currently used by biologists for data extraction and hypothesis formation

Model reduction for stochastic CaMKII reaction kinetics in synapses by graph-constrained correlation dynamics.

A stochastic reaction network model of Ca(2+) dynamics in synapses (Pepke et al PLoS Comput. Biol. 6 e1000675) is expressed and simulated using rule-based reaction modeling notation in dynamical grammars and in MCell. The model tracks the response of calmodulin and CaMKII to calcium influx in synapses. Data from numerically intensive simulations is used to train a reduced model that, out of sample, correctly predicts the evolution of interaction parameters characterizing the instantaneous probability distribution over molecular states in the much larger fine-scale models. The novel model reduction method, 'graph-constrained correlation dynamics', requires a graph of plausible state variables and interactions as input. It parametrically optimizes a set of constant coefficients appearing in differential equations governing the time-varying interaction parameters that determine all correlations between variables in the reduced model at any time slice