**DEEP LEARNING FOR MEDICAL DATA**

Andrew Beam, PhD

Senior Fellow/Head of Machine Learning

Flagship Pioneering

twitter: @AndrewLBeam

**WHAT IS DEEP LEARNING?**

#
**What is ****Artificial**** Intelligence?**

#
**What is Machine Learning****?**

Machine learning is a class of algorithms that learn how to do a task directly from data

Data = features (aka variables or inputs) and labels (aka the 'right' answer or outputs)

The algorithm is 'trained' to produce the correct output for a given input

#
**What is Machine Learning****?**

Features

ML Algorithm

Label

Cat

Dog

#
**What is Machine Learning****?**

Features

ML Algorithm

Label

“(Revenge of the Sith) marks a distinct improvement on the last two episodes, but only in the same way that dying from natural causes is preferable to crucifixion.”

Sentiment:

Negative

#
**What is Machine Learning****?**

Features

ML Algorithm

Label

"I'm sorry Dave,

I can't do that"

#
**What is Machine Learning****?**

Features

ML Algorithm

Label

"I'm sorry Dave,

I can't do that"

ML = box that takes input and produces output

#
**What is Machine Learning****?**

Features

ML Algorithm

Label

"I'm sorry Dave,

I can't do that"

ML = box that takes input and produces output

**WHAT IS DEEP LEARNING?**

Deep learning is a specific kind of **machine learning**

- Machine learning automatically learns relationships using data

- Deep learning refers to large *neural networks*

- These neural networks have millions of parameters and hundreds of *layers* (e.g. they are structurally deep)

- **Most important**: Deep learning is not magic!

**WHAT IS A NEURAL NET?**

**NEURAL NETWORK STRUCTURE**

**NEURAL NETWORK STRUCTURE**

Say we want to build a model to predict the likelihood of a have a heart attack (MI) based on blood pressure (BP) and BMI

**NEURAL NET STRUCTURE**

A neural net is a modular way to build a classifier

Inputs

Output

Probability of MI

**WHAT IS AN ARTIFICIAL NEURON?**

The neuron is the basic functional unit a neural network

Inputs

Output

Probability of MI

**WHAT IS AN ARTIFICIAL NEURON?**

The neuron is the basic functional unit a neural network

A neuron does two things, and only two things

**WHAT IS AN ARTIFICIAL NEURON?**

The neuron is the basic functional unit a neural network

Weight for

A neuron does two things, and only two things

Weight for

1) Weighted sum of inputs

**WHAT IS AN ARTIFICIAL NEURON?**

The neuron is the basic functional unit a neural network

Weight for

A neuron does two things, and only two things

Weight for

1) Weighted sum of inputs

2) Nonlinear transformation

**WHAT IS AN ARTIFICIAL NEURON?**

is known as the *activation* function

Sigmoid

Hyperbolic Tangent

**WHAT IS AN ARTIFICIAL NEURON?**

**Summary**: A neuron produces a single number that is a nonlinear transformation of its input connections

A neuron does two things, and only two things

= a number

**WHAT IS AN ARTIFICIAL NEURON?**

**Summary**: A neuron produces a single number that is a nonlinear transformation of its input connections

A neuron does two things, and only two things

= a number

**This simple formula allows for an amazing amount of expressiveness**

# PERCEPTRON BY HAND

**PERCEPTRONS**

Let's say we'd like to have a single neuron learn a function

y

X1 | X2 | y |
---|---|---|

0 | 0 | 0 |

0 | 1 | 1 |

1 | 0 | 1 |

1 | 1 | 1 |

Observations

**PERCEPTRONS**

How do we make a prediction for each observations?

y

X1 | X2 | y |
---|---|---|

0 | 0 | 0 |

0 | 1 | 1 |

1 | 0 | 1 |

1 | 1 | 1 |

Assume we have the following values

w1 | w2 | b |
---|---|---|

1 | -1 | -0.5 |

Observations

**Predictions**

For the first observation:

Assume we have the following values

w1 | w2 | b |
---|---|---|

1 | -1 | -0.5 |

**Predictions**

For the first observation:

Assume we have the following values

w1 | w2 | b |
---|---|---|

1 | -1 | -0.5 |

First compute the weighted sum:

**Predictions**

For the first observation:

Assume we have the following values

w1 | w2 | b |
---|---|---|

1 | -1 | -0.5 |

First compute the weighted sum:

Transform to probability:

**Predictions**

For the first observation:

Assume we have the following values

w1 | w2 | b |
---|---|---|

1 | -1 | -0.5 |

First compute the weighted sum:

Transform to probability:

Round to get prediction:

**Predictions**

Putting it all together:

Assume we have the following values

w1 | w2 | b |
---|---|---|

1 | -1 | -0.5 |

X1 | X2 | y | h | p | |
---|---|---|---|---|---|

0 | 0 | 0 | -0.5 | 0.38 | 0 |

0 | 1 | 1 | |||

1 | 0 | 1 | |||

1 | 1 | 1 |

Fill out this table

**Predictions**

Putting it all together:

Assume we have the following values

w1 | w2 | b |
---|---|---|

1 | -1 | -0.5 |

X1 | X2 | y | h | p | |
---|---|---|---|---|---|

0 | 0 | 0 | -0.5 | 0.38 | 0 |

0 | 1 | 1 | -1.5 | 0.18 | 0 |

1 | 0 | 1 | 0.5 | 0.62 | 1 |

1 | 1 | 1 | -0.5 | 0.38 | 0 |

Fill out this table

**Room for Improvement**

Our neural net isn't so great... how do we make it better?

What do I even mean by better?

**Room for Improvement**

Let's define how we want to *measure* the network's performance.

There are many ways, but let's use *squared-error*:

**Room for Improvement**

Let's define how we want to *measure* the network's performance.

There are many ways, but let's use *squared-error*:

Now we need to find values for that make this error as small as possible

**ALL OF ML IN ONE SLIDE**

Our task is *learning *values for such the the difference between the predicted and actual values is as small as possible.

**Learning from Data**

So, how we find the "best" values for

**Learning from Data**

So, how we find the "best" values for

hint: calculus

**Learning from Data**

Recall (without PTSD) that the *derivative* of a function tells you how it is changing at any given location.

If the derivative is positive, it means it's going up.

If the derivative is negative, it means it's going down.

**Learning from Data**

Simple strategy:

- Start with initial values for

- Take partial derivatives of loss function

with respect to

- Subtract the derivative (also called the *gradient)* from each

**Learning from Data**

Simple strategy:

- Start with initial values for

- Take partial derivatives of loss function

with respect to

- Subtract the derivative (also called the *gradient)* from each

To the whiteboard!

**Learning Rules for each Parameter**

Gradient for

Gradient for

Gradient for

Update for

Update for

Update for

**Learning Rules for each Parameter**

Gradient for

Gradient for

Gradient for

Update for

Update for

Update for

Fill in new table!

https://bit.ly/2ux5DLJ

**Learning Rules for each Parameter**

Gradient for

Gradient for

Gradient for

Update for

Update for

Update for

Fill in new table!

https://bit.ly/2ux5DLJ

Solution:

https://bit.ly/2FHpH4z

**THE BACKPROPAGATION ALGORITHM**

**A Simple Perceptron in R**

```
train <- function(X,y,w,b,iter=10,lr=1) {
w_new <- w
b_new <- b
for(i in 1:iter) {
preds <- plogis(X %*% w_new + b_new)
grad_w1 <- (preds - y)*preds*(1 - preds)*X[,1]
grad_w2 <- (preds - y)*preds*(1 - preds)*X[,2]
grad_b <- (preds - y)*(preds*(1 - preds))
w_new[1] <- w_new[1] - lr*sum(grad_w1)
w_new[2] <- w_new[2] - lr*sum(grad_w2)
b_new <- b_new - lr*sum(grad_b)
error <- (y - preds)^2
print(paste0("Error at iteration ",i,": ",mean(error)))
}
return(list(w=w_new,b=b_new))
}
X <- rbind(c(0,0),c(0,1),c(1,0),c(1,1))
y <- c(0,1,1,1)
w <- as.vector(c(1,-1))
b <- -0.5
train(X,y,w,b)
```

https://bit.ly/2JLDJ9m

**Another Example**

X1 | X2 | y |
---|---|---|

0 | 0 | 0 |

0 | 1 | 0 |

1 | 0 | 0 |

1 | 1 | 1 |

**Final Example**

X1 | X2 | y |
---|---|---|

0 | 0 | 0 |

0 | 1 | 1 |

1 | 0 | 1 |

1 | 1 | 0 |

**What Happened?**

Why didn't this work?

**What Happened?**

Why didn't this work?

Is this relationship "harder" in some sense?

**What Happened?**

Why didn't this work?

Is this relationship "harder" in some sense?

Let's plot it and see.

**NEURAL NETWORK STRUCTURE**

Inputs

Output

Neural nets are organized into layers

Probability of MI

**NEURAL NETWORK STRUCTURE**

Inputs

Output

Neural nets are organized into layers

Probability of MI

**NEURAL NETWORK STRUCTURE**

Inputs

Output

Input Layer

Neural nets are organized into layers

Probability of MI

**NEURAL NETWORK STRUCTURE**

Inputs

Output

Neural nets are organized into layers

1st Hidden Layer

Input Layer

Probability of MI

**NEURAL NETWORK STRUCTURE**

Inputs

Output

Neural nets are organized into layers

A single hidden unit

1st Hidden Layer

Input Layer

Probability of MI

**NEURAL NETWORK STRUCTURE**

Inputs

Output

Input Layer

Neural nets are organized into layers

1st Hidden Layer

A single hidden unit

2nd Hidden Layer

Probability of MI

**NEURAL NETWORK STRUCTURE**

Inputs

Output

Input Layer

Neural nets are organized into layers

1st Hidden Layer

A single hidden unit

2nd Hidden Layer

Output Layer

Probability of MI

**IN CLASS ASSIGNMENT**

**MODERN DEEP LEARNING**

Neural networks are one of the oldest ideas in machine learning and AI

- Date back to 1940s

- Long history of "hype" cycles - boom and bust

- Were *not* state of the are machine learning technique for most of their existence

- Why are they popular now?

**MODERN DEEP LEARNING**

Several key advancements have enabled the modern deep learning revolution

GPU enable training of huge neural nets on extremely large datasets

Several key advancements have enabled the modern deep learning revolution

**MODERN DEEP LEARNING**

**Transfer Learning**

Train big model

on large dataset

Refine model

on smaller dataset

Several key advancements have enabled the modern deep learning revolution

Methodological advancements have made deeper networks easier to train

**Architecture**

**Optimizers**

**Activation Functions**

**MODERN DEEP LEARNING**

Several key advancements have enabled the modern deep learning revolution

Easy to use frameworks dramatically lower the barrier to entry

**Automatic differentiation** allows easy prototyping

**MODERN DEEP LEARNING**

**+**

**Deep Learning Comes of Age**

**CONVOLUTIONAL NEURAL NETWORKS**

**CONVOLUTIONAL NEURAL NETS (CNNs)**

Dates back to the late 1980s

- Responsible for Deep Learning revival
- Invented by in 1989 Yann Lecun at Bell Labs - "Lenet"
- Integrated into handwriting recognition systems

in the 90s - Huge flurry of activity after the Alexnet paper

**THE BREAKTHROUGH (2012)**

**Imagenet Database**

- Millions of labeled images
- Objects in images fall into 1 of a possible 1,000 categories
- Relatively high-resolution
- Bounding boxes giving exact location of object - useful for both classification and localization

** Large Scale Visual **

**Recognition Challenge (ILSVRC)**

- Annual Imagenet Challenge starting in 2010
- Successor to smaller PASCAL VOC challenge
- Many tracks including classification and localization
- Standardized training and test set. Competitors upload predictions for test set and are automatically scored

**THE BREAKTHROUGH (2012)**

Pivotal event occurred in 2012 which laid the blueprint for successful deep learning model

- Massive amounts of labeled images
- Training with GPUs
- Methodological innovations that enabled training deeper networks while minimizing overfitting

**THE BREAKTHROUGH (2012)**

In 2011, a misclassification rate of 25% was near state of the art on ILSVRC

In 2012, Geoff Hinton and two graduate students, Alex Krizhevsky and Ilya Sutskever, entered ILSVRC with one of the first deep neural networks trained on GPUs, now known as "**Alexnet**"

Result: An error rate of 16%, nearly half what the second place entry was able to achieve.

The computer vision world immediately took notice

**THE ILSVRC AFTERMATH (2012-2014)**

Alexnet paper has ~ 37,000 citations since being published in 2012!

**Most algorithms expect "tabular" data**

**WHY CNNS WORK**

y | X1 | X2 | X3 | X4 |
---|---|---|---|---|

0 | 7 | 52 | 17 | 654 |

0 | 23 | 2752 | 4 | 1 |

1 | 786 | 27 | 0 | 5 |

0 | 354 | 7527 | 89 | 68 |

**The problem with tabular data**

**What is this a picture of?**

**WHY CNNS WORK**

**What is this a picture of?**

**The problem with tabular data**

**WHY CNNS WORK**

**What is this a picture of?**

**Tabular data throws away too much information!**

**The problem with tabular data**

**WHY CNNS WORK**

**CONVOLUTIONAL NEURAL NETS**

Images are just 2D arrays of numbers

Goal is to build f(image) = 1

**CONVOLUTIONAL NEURAL NETS**

CNNs look at small connected groups of pixels using "filters"

Image credit: http://deeplearning.stanford.edu/wiki/index.php/Feature_extraction_using_convolution

Images have a *local correlation structure*

Near by pixels are likely to be more similar than pixels that are far away

CNNs exploit this through convolutions of small image patches

**WHY DO CNNs WORK SO WELL?**

- Based on solid image priors
- Exploit properties of images, e.g. local correlations and invariances
- Mimic generative distribution with augmentation to reduce over fitting
- Results in end-to-end visual recognition system trained with SGD on GPUs: pixels in -> classifications out

CNNs exploit strong prior information about images

**ALPHAGO DISCUSSION**

**DEEP LEARNING HAS MASTERED GO**

Source: https://deepmind.com/blog/alphago-zero-learning-scratch/

Human data no longer needed

**DEEP LEARNING HAS MASTERED GO**

**DEEP LEARNING HAS MASTERED GO**

**SUMMARY & CONCLUSIONS**

**CONCLUSIONS**

- Deep learning models are like legos, but you need to know what blocks you have and how they fit together
- Could potentially impact many fields -> understand concepts so you have deep learning "insurance"
- Impact of medical imaging seems inevitable
- Prereqs: Data (lots) + GPUs (more = better)

**Review Articles**

**Additional Resources**

http://beamandrew.github.io

#### HMS Computational Medicine Lecture (March 2020)

By beamandrew

# HMS Computational Medicine Lecture (March 2020)

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