Content uploaded by Douglas G. Moore
Author content
All content in this area was uploaded by Douglas G. Moore on Aug 09, 2019
Content may be subject to copyright.
Pattern Regeneration in Coupled Networks
Douglas G. Moore1, Sara I. Walker1and Michael Levin2
1BEYOND Center, Arizona State University, Tempe, AZ 85281
2Allen Discovery Center, Tufts University, Medford, MA 02155
douglas.g.moore@asu.edu
Abstract
Many organisms such as planaria, axolotls and deer exhibit
prodigious regenerative abilities, being capable of regenerat-
ing complex organs or entire body plans. An understanding
of how these organisms store and modify their morphological
patterning information is necessary to identify modes of con-
trol and intervention. Insight into this process is key to the
development of novel biomedical applications. In this work,
we present the CANN(k) model: an abstract computational
model of pattern regeneration which couples an artificial neu-
ral network (ANN) with a k-color cellular automaton (CA).
The ANN provides a global information processing system
which generates state-dependent update rules for the CA. The
CANN(k) models are constructed to generate target patterns
which are stable under perturbations of the pattern. We gen-
erate ensembles of CANN(4) models for each of the 4-color
patterns, assess their sensitivity to changes of the ANN struc-
ture. This provides a novel model for understanding the im-
portant biological phenomenon of neural control of cellular
morphogenesis in development or regeneration.
Introduction
Many animals are capable of regenerating complex struc-
tures after amputation (Birnbaum and S´
anchez Alvarado,
2008). For example, planaria can regenerate their entire
body from a fragment as small as 1/279 of the original an-
imal (Handberg-Thorsager et al., 2008). Control of cellular
activity toward the creation and repair of complex anatom-
ical patterns is a central aspect of evolutionary biology as
well as birth defects, traumatic injury and cancer. The abil-
ity to intervene upon and effectively control these processes
is key to developing novel biomedical applications (Baddour
et al., 2012; Levin, 2011). Modes of control over the process
of large-scale, complex homeostasis are still lacking, despite
significant development in our understanding of the molec-
ular mechanisms necessary for these processes (Stocum and
Cameron, 2011). Specifically, while it is known that the ner-
vous system can guide complex morphogenesis (Herrera-
Rincon et al., 2017), the control dynamics of this process
are very poorly understood. An important open question is
whether regenerative processes require large-scale informa-
tion about the current state of the organism, or if information
local to each cell or tissue is sufficient. The answer to this
question will suggest the ideal level and method of interven-
tion necessary to control regenerative processes.
This work presents an abstract model of pattern regener-
ation that combines both global information processing and
local update rules to generate stable target patterns.
Methods and Results
The model of pattern regeneration considered here, referred
to as a CANN(k) model, is composed of two parts: a k-color
cellular automaton (CA), and a feed-forward artificial neu-
ral network (ANN). The k-color CA is a one-dimensional
array of cells, each of which can be in one of kstates (or col-
ors). The state of each cell is updated according to a nearest-
neighbor rule with the same rule applied to each cell concur-
rently. Traditionally, a fixed rule is applied at each time step,
and the process is iterated to generate a trajectory of states
that terminates in an attractor cycle, a sequence of states that
repeats indefinitely. The distinguishing characteristic of a
CANN(k) model is that the rule used at each time step is not
fixed. Instead, the state of the CA is provided as input to
the CANN(k)’s ANN which outputs the CA update rule to
use at the current time step. Another important choice for
these lattice-type models is the boundary conditions for the
ends of the CA lattice. Here we employ a fixed, open bound-
ary condition where each boundary cell uses an unchanging
“white” cell for its missing neighbor’s state. See Figure 1a
for a schematic representation of a CANN(k) model.
The objective is to better understand how morphological
patterns can be faithfully regenerated when the pattern is
perturbed. We say that the pattern, or particular sequence of
colored CA states, regenerates if it is recovered as a fixed-
point attractor under the model’s dynamics. If the pattern is
perturbed, will the system ultimately return to and retain the
desired pattern? In particular, given a desired target pattern
and a set of perturbations, we wish to construct and analyze
a CANN(k) model with the following three properties:
1. The target pattern is a fixed-point attractor of the dynamic.
2. Every admissible perturbation of the target pattern ulti-
mately converges to that target pattern.
3. No cell that is colored becomes white in the next time step
along any of the perturbed trajectories.
We employed a simulated annealing (SA) algorithm (Kirk-
patrick et al., 1983) to construct CANN(k) models which
satisfy all three criteria. The decision to employ SA for
training was based primarily on the constraint-based spec-
ification of the problem. A deterministic algorithm, such
as back-propagation, is ill-suited here as we are primarily
interested in the final pattern generated rather than the par-
ticular sequence of states in the time series, and we do no
have a well-defined training set. One advantage of the SA
approach is each model is endowed with an energy which
quantifies how well it solves the problem at hand. This pro-
vides a way of quantifying the difference in effectiveness
between two models. This energy is, in our case, defined in
terms of three factors which mirror the constraints above:
1. δis the fraction of cells of the target pattern that are not
fixed by the CANN(k) update rule.
2. κis the fraction of observed states that do not transition
into the target state after some number of time steps.
3. τis the fraction of observed states which introduce new
white cells.
We then define the energy as
E=αδ +βκ +γτ (1)
with 0≤α, β, γ ≤1and δ+κ+γ= 1. For this work,
we chose α=β= 4/9, and γ= 1/9, though these can
be adjusted freely. There is no strict guarantee that the SA
algorithm will find a solution; however, the energy in eq. (1)
ensures that the degenerate global minimum satisfies our de-
sired heuristic properties.
We generated ensembles of 100 CANN(4) models for
each of the 729 possible 6cell, 4-color ( , , and )
target patterns with no white cells. We limited the set of pat-
tern perturbations which must converge to the target pattern
to amputations of the desired pattern. An amputation is the
removal of a contiguous region from either end of the target
pattern, i.e. setting cells on either end of the array to white.
This limited type of perturbation roughly models a common
type of intervention biologists perform, and from which re-
generative organisms should recover. An example of an am-
putation and regeneration process is depicted in Figure 1b.
We then assessed the sensitivity of the resulting CANN(4)
models to small perturbations of the underlying ANN. This is
defined as the average change in energy of the model when
either one weight or one threshold of the ANN is modified,
and is distinct from the types of perturbations applied to the
CA state discussed above. We find that 6-cell CANN(4)
models exhibit an average sensitivity of 0.020 ±0.009. This
suggests that the target pattern remains a fixed-point under
small perturbations of the ANN, but that the system looses
the ability to properly regenerate from all amputations.
Subsequent work will include improving the training al-
(a) A CANN Model (b) Trajectory
Figure 1: (a) A 3-cell CANN(k) model consists of a cellular au-
tomaton (CA) and a feed-forward, artificial neural network. (i.) At
each time step, the state of the CA is provided as input into the
ANN. (ii.) The ANN processes that input and generates k3outputs
with values {0,...,k −1}. (iii.) The outputs are assembled into
a CA rule and (iv.) used to update the state of the CA. (b) An Ex-
ample 6-cell CANN(4) Trajectory. The top-most row represents
an extreme amputation (setting colored cells to white) of the target
pattern (bottom row). Each row from top to bottom represents suc-
cessive updates of the state according to the underlying CANN(4)
model. The final row is the fully regenerated, stable target pattern.
gorithms, either by choosing an alternative approach or
modifying the constraint-based energy function, assessing
the scalability of this approach, and performing a detailed
sensitivity analyses of generalized models.
Acknowledgements
This work was supported by the Templeton Foundation
(TWCF0089/AB55 and TWCF0140). M.L. gratefully ac-
knowledges support by the Allen Discovery Center program
through The Paul G. Allen Frontiers Group (12171).
References
Baddour, J. A., Sousounis, K., and Tsonis, P. A. (2012). Organ
repair and regeneration: an overview. Birth defects research.
Part C, Embryo today: reviews, 96(1):1–29.
Birnbaum, K. D. and S ´
anchez Alvarado, A. (2008). Slicing
across kingdoms: regeneration in plants and animals. Cell,
132(4):697–710.
Handberg-Thorsager, M., Fernandez, E., and Salo, E. (2008). Stem
cells and regeneration in planarians. Frontiers in bioscience:
a journal and virtual library, 13:6374–6394.
Herrera-Rincon, C., Pai, V. P., Moran, K. M., Lemire, J. M., and
Levin, M. (2017). The brain is required for normal muscle
and nerve patterning during early xenopus development. Na-
ture communications, 8(1):587.
Kirkpatrick, S., Gelatt, Jr, C. D., and Vecchi, M. P. (1983). Op-
timization by simulated annealing. Science, 220(4598):671–
680.
Levin, M. (2011). The wisdom of the body: future techniques and
approaches to morphogenetic fields in regenerative medicine,
developmental biology and cancer. Regenerative medicine,
6(6):667–673.
Stocum, D. L. and Cameron, J. A. (2011). Looking proximally and
distally: 100 years of limb regeneration and beyond. Devel-
opmental dynamics: an official publication of the American
Association of Anatomists, 240(5):943–968.