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How to Make a Computer Think for You Jeff Knisley, The Institute for Quantitative Biology, East Tennessee State University ALABAMA MAA STATE DINNER AND LECTURE, Feb, 2006 Soma Dendrites Synapses Axon This is a Neuron Signals Propagate from Dendrites to Soma Signals Decay at

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how to make a computer think for you

How to Make a Computer Think for You

Jeff Knisley, The Institute for Quantitative Biology, East Tennessee State University


this is a neuron





This is a Neuron

Signals Propagate from

Dendrites to Soma

Signals Decay at

Soma if below a

Certain threshold

signals may arrive close together
Signals May Arrive Close Together

If threshold exceeded,

then neuron “fires,”

sending a signal

along its axon.

artificial neural network ann
Artificial Neural Network (ANN)
  • Made of artificial neurons, each of which
    • Sums inputs from other neurons
    • Compares sum to threshold
    • Sends signal to other neurons if above threshold
  • Synapses have weights
    • Model relative ion collections
    • Model efficacy (strength) of synapse
artificial neuron
Artificial Neuron


firing function




hopfield network

Choose ith neuron at random and calculate its new state

Hopfield Network




with weights

wij between ith

and jth neurons

Blue = 1

White = 0


Define the energy to be

Theorem: If the weights are symmetric, then the Energy

decreases each time a neuron fires.

  • Handwriting Recognition
  • Universal Classifier
  • Expert Systems
    • Rule-based rather than sequential programs
    • Air traffic control, Industrial Controls
  • Robotics
    • Usually using a 3-layer network
3 layer neural network
3 Layer Neural Network

The output layer may

consist of a single





(is usually much larger)

neural nets can think
Neural Nets can “Think”
  • A Neural Network can “think” for itself
    • Can be trained (programmed) to make decisions
    • Can be trained to classify information

This tiny 3-Dimensional

Artificial Neural Network,

modeled after neural networks

in the human brain, is helping

machines better visualize

their surroundings.

the mars rovers
The Mars Rovers
  • Must choose where to explore
    • Programmed to avoid “rough” terrain
    • Programmed to choose “smooth” terrain
  • ANN decides between “rough” and “smooth”
    • “rough” and “smooth” are ambiguous
    • Programmingis by means of many “examples”(lessons)
illustration colors terrains










Illustration: Colors = Terrains
  • As a robot moves, it defines 8 squares of size A that define directions it can move in
    • It should avoid red (rough) terrain
    • It should prefer green (smooth) terrain
    • It should be indifferent to blue (normal) terrain
  • It is impossible to program every possible shade and variation
    • Instead, a neural network is constructed
    • Terrain Block – Color class input/output patterns are used to train the network
train ann to classify colors


we have a








Train ANN to Classify Colors

Training Set

Input OutputTerrain <R,G,B>












ann s can also think for us
ANN’s Can Also Think for Us
  • Mars Rovers do what Humans can do better
    • They do not “learn” on their own
    • They are taught by Humans who could make the same or better decisions in their place
    • They can use their “learning” independently
  • What about problems Humans can’t solve at all
    • Neural Networks can be used as savants dedicated to a single problem too complex for humans to decipher
    • Examples
      • Agent-Based Modeling
      • RNA, Protein Structures, DNA analysis
      • Data Mining
division of labor in wasps nests
Division of Labor in Wasps Nests
  • A Wasp can alternate between laborer, water forager, and pulp forager
    • Hypothesis: Individual wasps choose roles so that total water in the nest reaches equilibrium
    • Hypothesis: Pulp production is maximized when total water in the nest is stable
  • Limited confirmation of Hypotheses
    • (Karsai and Wenzel, 2002) System of 3 ode’s
    • (Karsai, *Phillips, and Knisley, 2005) Computer Simulation
ann wasp societies
ANN Wasp Societies
  • Problems with current models
    • Role assigned randomly w.r.t. a Weibull distribution
    • Parameters selected so model “works”
  • ANN: Role is a decision of each wasp
    • A wasp is a special type of Artificial Neuron
      • Wasp decides its own role
      • Wasp learns to make good choices
    • System is deterministic yet unpredictable

“I’m empty, I need water!”

“No luck, so I’m a water forager.”


“I’m so good at getting water, I think I should go forage for pulp.”

“I have water!”

division of labor by choice
Division of Labor by choice?
  • Numbers of foragers goes up and down
  • But water level in nest becomes stable
data mining
Data Mining
  • We often consider very large data sets
    • Microarrays contain about 20,000 data points
    • Typical studies use 70 – 100 microarrays
    • Most of the data is not relevant
  • ANN’s can be trained to find hidden patterns
    • Input layer = Genes
    • Network is trained repeatedly with microarrays collected in various physiological states
    • ANN’s predict which genes are responsible for a given state
ann s in data mining
ANN’s in Data Mining
  • Each neuron acts as a “linear classifier”
  • Competition among neurons via nonlinear firing function = “local linear classifying”
  • Method for Genes:
    • Train Network until it can classify between control and experimental groups
    • Eliminating weights sufficiently close to 0 does not change local classification scheme
  • First results obtained with a Perceptron ANN
simple perceptron model
Simple Perceptron Model

x1 = Gene 1


x2 = Gene 2



xn = Gene n

The output is the “physiological state” due to the relative gene expression levels used as inputs.

simple perceptron model25
Simple Perceptron Model
  • Features
    • The wi measure gene “significance”
    • Detects genes across n samples & references
    • Ref: Artificial Neural Networks for Reducing the Dimensionality of Gene Expression Data, A. Narayanan, et al. 2004.
  • Drawbacks
    • The Perceptron is a globaly linear classifier (i.e., only classifies linearly separable data)
    • We are now using a more sophisticated model
linearly separable data
Linearly Separable Data

Separation using Hyperplanes

how do we select w s
How do we select w’s
  • Define an energy function
    • x1,…,xn are inputs, y = output
    • t1,…,tm are the outputs associated with the patterns to be “learned”
    • y = s( S wixi - q) for a perceptron
    • Key: Neural networks minimize energy
back propagation
Back Propagation
  • Minimize the Energy Function
    • Choose wi so that
    • In practice, this is hard
  • Back Propagation: s = s(1-s)
    • For each pattern ti
      • Feed Forward and Calculate E
      • Increment weights using a delta rule:
    • Repeat until E is sufficiently close to 0
perceptron for microarray datamining
Perceptron for Microarray DataMining
  • Remove % of genes with synaptic weights that are close to 0
  • Create ANN classifier on reduced arrays
  • Repeat 1 and 2 until only the genes that most influence the classifer problem remain

Remaining genes are most important in classifying experimentals versus controls

functional viewpoint
Functional Viewpoint
  • ANN is a mapping f: Rn→ R
    • Can we train perceptron so that f(x1,…,xn) =1 if x vector is from a control and f(x1,…,xn) =0 if x is from an experimental?
    • Answer: Yes if data can be linearly separated, but no otherwise unless we use better ANN’s!
  • General ANN’s also have problems
    • Spurious states: (sometimes ANN’s get the wrong answer)
    • Hard Margins: Training set must be perfect
how do we select w s33
How do we select w’s
  • Define an energy function
    • t vectors are the information to be “learned”
    • Neural networks minimize energy
    • The “information” in the network is equivalent to the minima of the total squared energy function
back propagation34
Back Propagation
  • Minimize the Energy Function
    • Choose wj and aj so that
    • In practice, this is hard
  • Back Propagation with cont. sigmoidal
    • Feed Forward and Calculate E
    • Modify weights using a d rule
    • Repeat until E is sufficiently close to 0
ann as classifer
ANN as Classifer
  • (Cybenko) For any e>0, the function f(x1,…,xn) =1 if x vector is from a control and f(x1,…,xn) =0 if x is from an experimental can be approximated to within e by a multilayer neural network.
  • The weights no longer have the one-to-one correspondence to genes, so we test significance using Monte Carlo techniques.
ann and monte carlo methods
ANN and Monte Carlo Methods
  • Monte Carlo methods have been a big success story with ANN’s
    • Error estimates with network predictions
    • ANN’s are very fast in the forward direction
  • Example: ANN+MC implement and outperform Kalman Filters (recursive linear filters used in Navigation and elsewhere)(De Freitas J. F. G., et. al., 2000)
recall multilayer network
Recall: Multilayer Network







ajcorrespond to genes,

but do not directly depend

on a single gene.

N Genes

N node



na ve monte carlo ann method
Naïve Monte Carlo ANN Method
  • Randomly choose subset S of genes
  • Train using Back Propagation
  • Prune based on values of wj (or aj , or both)
  • Repeat 2-3 until a small subset of S remains
  • Increase “count” of genes in small subset
  • Repeat 1-5 until each gene has 95% probability of appearing at least some minimum number of times in a subset
  • Most frequent genes are the predicted
additional considerations
Additional Considerations
  • If a gene is up-regulated or down-regulated for a certain condition, then put it into a subset in step 1 with probability 1.
  • This is a simple-minded Bayesian method. Bayesian analysis can make it much better.
  • Algorithm distributes naturally across a multi-processor cluster or machine
    • Choose the subsets first
    • Distribute subsets to different machines
    • Tabulate the results from all the machines
  • ANN’s are designed to make decisions in similar fashion to how we make decisions
    • In this way, they can “think” for themselves
    • Can be considered supplements to existing hardware and software tools
  • The ability of ANN’s to make decisions allows them to think for us as well!
    • They can find patterns in large data sets that we humans would likely never uncover
    • They can “think” for days/months on end

Cybenko, G. Approximation by Superpositions of a sigmoidal function, Mathematics of Control, Signals, and Systems, 2(4),1989, p. 303-314.

De Freitas J. F. G., et. al. Sequential Monte Carlo Methods To Train Neural Network Models. Neural Computation, Volume 12, Number 4, 1 April 2000, pp. 955-993(39)

L. Glenn and J. Knisley, Solutions for Transients in Arbitrarily Branching and Tapering Cables, Modeling in the Neurosciences: From Biological Systems to Neuromimetic Robotics, ed. Lindsay, R., R. Poznanski, G.N.Reeke, J.R. Rosenberg, and O.Sporns, CRC Press, London, 2004.

A. Narayan, et. al Artificial Neural Networks for Reducing the Dimensionality of Gene Expression Data. Neurocomputing, 2004.