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Neural Network Approaches for Reducing Healthcare Costs Kimberly Robasky Translational Research Scientist, Renaissance Computing Institute Adjunct Professor, Department of Genetics Adjunct Professor, School of Information and Library Science Core Faculty, Carolina Health Informatics Program University of North Carolina, Chapel Hill [email protected]

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Page 1: Neural Network Approaches for Reducing Healthcare Costs · 2019-06-21 · Neural Network Approaches for Reducing Healthcare Costs Kimberly Robasky Translational Research Scientist,

Neural Network Approachesfor Reducing Healthcare Costs

Kimberly RobaskyTranslational Research Scientist, Renaissance Computing InstituteAdjunct Professor, Department of GeneticsAdjunct Professor, School of Information and Library ScienceCore Faculty, Carolina Health Informatics ProgramUniversity of North Carolina, Chapel [email protected]

mailto:[email protected]
Page 2: Neural Network Approaches for Reducing Healthcare Costs · 2019-06-21 · Neural Network Approaches for Reducing Healthcare Costs Kimberly Robasky Translational Research Scientist,

Who is RENCI?

Carolina is at “the epicenter of computer science and data science” because of the work of the Renaissance Computing Institute

~ Executive Vice Chancellor and Provost Robert A. BlouinUNC University Gazette, June 2019

Page 3: Neural Network Approaches for Reducing Healthcare Costs · 2019-06-21 · Neural Network Approaches for Reducing Healthcare Costs Kimberly Robasky Translational Research Scientist,

Key Partners

Page 4: Neural Network Approaches for Reducing Healthcare Costs · 2019-06-21 · Neural Network Approaches for Reducing Healthcare Costs Kimberly Robasky Translational Research Scientist,

What is Translational Science?

https://www.nsf.gov/eng/iip/innovation.pdf

“Valley of Death”

Source: Haendel, et al

Often depicted as an iterative process from basic science and engineering research at the start to production and marketing at the end.(NSF, IBID)

Translational research may involve prototyping, proof-of-concept tests, or scale-up and implementation (NSF 2010b)

https://www.nsf.gov/eng/iip/innovation.pdf
Page 5: Neural Network Approaches for Reducing Healthcare Costs · 2019-06-21 · Neural Network Approaches for Reducing Healthcare Costs Kimberly Robasky Translational Research Scientist,

Overview

Promise of Precision Medicine

Challenge of Clinical Trials

Burdens and Blessings of Genomic Data

Reducing Healthcare Costs with Emerging Technologies

Page 6: Neural Network Approaches for Reducing Healthcare Costs · 2019-06-21 · Neural Network Approaches for Reducing Healthcare Costs Kimberly Robasky Translational Research Scientist,

Precision Medicine: One Size does not fit all

Source: Quiagen

Page 7: Neural Network Approaches for Reducing Healthcare Costs · 2019-06-21 · Neural Network Approaches for Reducing Healthcare Costs Kimberly Robasky Translational Research Scientist,

Clinical Trials In a Nutshell

Phase ApproximateSuccess Rate

1 70%

2 33%

3 25-30%

Phase1-3: 6-7%

• Most expensive phase of failure: Phase 4

• Most common source of PMA failure: hepatotoxicity [source: FDA]

Effect on body

Safety10+ subjects, weeks

Effectiveness

100+ subjects, months

Scale-up

1,000+ subjects, years

Long term safety

continuous

Phase 0

Phase 1

Phase 2

Phase 3

Phase 4

Page 8: Neural Network Approaches for Reducing Healthcare Costs · 2019-06-21 · Neural Network Approaches for Reducing Healthcare Costs Kimberly Robasky Translational Research Scientist,

NDA: New Drug Approval Application Timeline

• Is it safe & effective? -trials

• Is the labelling appropriate? (prescriptive)

• Are the manufacturing practices adequate?-GMP

Page 9: Neural Network Approaches for Reducing Healthcare Costs · 2019-06-21 · Neural Network Approaches for Reducing Healthcare Costs Kimberly Robasky Translational Research Scientist,

How Can We 1. Reduce Clinical Trial Costs and 2. Improve Outcomes?

Page 10: Neural Network Approaches for Reducing Healthcare Costs · 2019-06-21 · Neural Network Approaches for Reducing Healthcare Costs Kimberly Robasky Translational Research Scientist,

Genomic Biomarkers Impact Survival

Cell 2015 161, 205-214DOI: (10.1016/j.cell.2015.03.030)

Copyright © 2015 Elsevier Inc. Terms and Conditions

Therapy Response Rate

Toxicity Long term survival

“Standard” chemotherapy

Lower Higher Lower

“Targeted” therapy

Higher Lower Moderate

http://www.elsevier.com/termsandconditions
Page 11: Neural Network Approaches for Reducing Healthcare Costs · 2019-06-21 · Neural Network Approaches for Reducing Healthcare Costs Kimberly Robasky Translational Research Scientist,

Clinical Panels

Solid and circulating tumor gene panels

Diagnostics for dermatology, cardiology, immunology, and more

Neonatal carrier screening panel

Clinical exomes, Oncology, neurology, others

Oncomine

Cancer panels, exomes, transcriptomes

Page 12: Neural Network Approaches for Reducing Healthcare Costs · 2019-06-21 · Neural Network Approaches for Reducing Healthcare Costs Kimberly Robasky Translational Research Scientist,

In Home Kits

Color: cancer risk

Celmatix: fertility

Page 13: Neural Network Approaches for Reducing Healthcare Costs · 2019-06-21 · Neural Network Approaches for Reducing Healthcare Costs Kimberly Robasky Translational Research Scientist,

More In Home Kits

Page 14: Neural Network Approaches for Reducing Healthcare Costs · 2019-06-21 · Neural Network Approaches for Reducing Healthcare Costs Kimberly Robasky Translational Research Scientist,

Is Genome Interpretation a Solved Problem?

Page 15: Neural Network Approaches for Reducing Healthcare Costs · 2019-06-21 · Neural Network Approaches for Reducing Healthcare Costs Kimberly Robasky Translational Research Scientist,

Genomic variant prioritization, reporting incidental findings: not a solved problem

The American Journal of Human Genetics 2016 98, 1067-

1076DOI: (10.1016/j.ajhg.2016.03.024)

Page 16: Neural Network Approaches for Reducing Healthcare Costs · 2019-06-21 · Neural Network Approaches for Reducing Healthcare Costs Kimberly Robasky Translational Research Scientist,

Why Is Genome Interpretation So Challenging?

Page 17: Neural Network Approaches for Reducing Healthcare Costs · 2019-06-21 · Neural Network Approaches for Reducing Healthcare Costs Kimberly Robasky Translational Research Scientist,

Genomic Data ExplosionGenomic Data Explosion

Page 18: Neural Network Approaches for Reducing Healthcare Costs · 2019-06-21 · Neural Network Approaches for Reducing Healthcare Costs Kimberly Robasky Translational Research Scientist,

Genomic Data ExplosionGenomic Data Explosion

Page 19: Neural Network Approaches for Reducing Healthcare Costs · 2019-06-21 · Neural Network Approaches for Reducing Healthcare Costs Kimberly Robasky Translational Research Scientist,

Genomic Data ExplosionGenomic Data Explosion

Page 20: Neural Network Approaches for Reducing Healthcare Costs · 2019-06-21 · Neural Network Approaches for Reducing Healthcare Costs Kimberly Robasky Translational Research Scientist,

Genomic Data ExplosionGenomic Data Explosion

Page 21: Neural Network Approaches for Reducing Healthcare Costs · 2019-06-21 · Neural Network Approaches for Reducing Healthcare Costs Kimberly Robasky Translational Research Scientist,

Genomic Data ExplosionGenomic Data Explosion

Page 22: Neural Network Approaches for Reducing Healthcare Costs · 2019-06-21 · Neural Network Approaches for Reducing Healthcare Costs Kimberly Robasky Translational Research Scientist,

Genomic Data ExplosionGenomic Data Explosion

Page 23: Neural Network Approaches for Reducing Healthcare Costs · 2019-06-21 · Neural Network Approaches for Reducing Healthcare Costs Kimberly Robasky Translational Research Scientist,

Genomic Data Explosion

Source: xcode

Genomic Data Explosion

Page 24: Neural Network Approaches for Reducing Healthcare Costs · 2019-06-21 · Neural Network Approaches for Reducing Healthcare Costs Kimberly Robasky Translational Research Scientist,

So Much Data!

90% of all data existing today was created in the last two years and…people create 2.5 quintillion bytes of data per day. (To visualize this number, according to a post from Yappn Corp, imagine covering the surface of the Earth with pennies — five times.)

~ Stan Ahalt, RENCI DirectorUNC University GazetteJune 2019

Page 25: Neural Network Approaches for Reducing Healthcare Costs · 2019-06-21 · Neural Network Approaches for Reducing Healthcare Costs Kimberly Robasky Translational Research Scientist,

What Can Help Overcome the Challenges of Genome Interpretation?

Page 26: Neural Network Approaches for Reducing Healthcare Costs · 2019-06-21 · Neural Network Approaches for Reducing Healthcare Costs Kimberly Robasky Translational Research Scientist,
Page 27: Neural Network Approaches for Reducing Healthcare Costs · 2019-06-21 · Neural Network Approaches for Reducing Healthcare Costs Kimberly Robasky Translational Research Scientist,

Standard Bioinformatics Visualizations

https://www.r-bloggers.com/7-interactive-bioinformatics-plots-made-in-python-and-r/

Page 28: Neural Network Approaches for Reducing Healthcare Costs · 2019-06-21 · Neural Network Approaches for Reducing Healthcare Costs Kimberly Robasky Translational Research Scientist,

Bill Gates to Francis Collins at ASHG 2017:

Good thing we're in a world now with Infinite compute and storage; geneticists are one of the few people in the world can fill it.

Page 29: Neural Network Approaches for Reducing Healthcare Costs · 2019-06-21 · Neural Network Approaches for Reducing Healthcare Costs Kimberly Robasky Translational Research Scientist,

Neural Network “Perceptron”, a.k.a, “Node”

Page 30: Neural Network Approaches for Reducing Healthcare Costs · 2019-06-21 · Neural Network Approaches for Reducing Healthcare Costs Kimberly Robasky Translational Research Scientist,

Simplified Neural Network: Many Nodes

f

f

f

f

f

f

f

f

Sharp teeth

Furry

Woof

Is Dog

Sharp teeth

Furry Woof Is Dog

1 1 1 1

1 0 1 1

0 1 0 0

Hidden Layer 1

Hidden Layer 2

Output Layer

Input Layer

Features Target

Training Data

Features

Page 31: Neural Network Approaches for Reducing Healthcare Costs · 2019-06-21 · Neural Network Approaches for Reducing Healthcare Costs Kimberly Robasky Translational Research Scientist,

Neural Network: Training a Discriminator

f

f

f

f

f

f

f

f

Pixel1

Pixel2

Pixel3

Is Fake

Pixel1 Pixel2 Pixel3 Is Fake

1 1 1 1

1 0 1 1

0 1 0 0

Hidden Layer 1

Hidden Layer 2

Output Layer

Input Layer

Features Target

Training Data

Page 32: Neural Network Approaches for Reducing Healthcare Costs · 2019-06-21 · Neural Network Approaches for Reducing Healthcare Costs Kimberly Robasky Translational Research Scientist,

Generative Adversarial Networks

Real Data

Discriminator (D)

Generator

NoiseGeneratedData

Legend

Neural Net

Was D fooled?

Page 33: Neural Network Approaches for Reducing Healthcare Costs · 2019-06-21 · Neural Network Approaches for Reducing Healthcare Costs Kimberly Robasky Translational Research Scientist,

Generative Adversarial Networks

Real Data

Discriminator (D)

Generator

NoiseGeneratedData

Legend

Neural Net

Was D fooled?

ForgerGoal: Minimize Discriminator’s accuracy

DetectiveGoal: Distinguish fake from real

Page 34: Neural Network Approaches for Reducing Healthcare Costs · 2019-06-21 · Neural Network Approaches for Reducing Healthcare Costs Kimberly Robasky Translational Research Scientist,

Can a NN learn how to make realistic data without labels?

Page 35: Neural Network Approaches for Reducing Healthcare Costs · 2019-06-21 · Neural Network Approaches for Reducing Healthcare Costs Kimberly Robasky Translational Research Scientist,

ThisPersonDoesNotExist.com

Page 36: Neural Network Approaches for Reducing Healthcare Costs · 2019-06-21 · Neural Network Approaches for Reducing Healthcare Costs Kimberly Robasky Translational Research Scientist,

WhichFaceIsReal.com

Page 37: Neural Network Approaches for Reducing Healthcare Costs · 2019-06-21 · Neural Network Approaches for Reducing Healthcare Costs Kimberly Robasky Translational Research Scientist,

WhichFaceIsReal.com

Page 38: Neural Network Approaches for Reducing Healthcare Costs · 2019-06-21 · Neural Network Approaches for Reducing Healthcare Costs Kimberly Robasky Translational Research Scientist,

Preliminary Simulated RNASeq Data

Manuscript In Preparation

Page 39: Neural Network Approaches for Reducing Healthcare Costs · 2019-06-21 · Neural Network Approaches for Reducing Healthcare Costs Kimberly Robasky Translational Research Scientist,

Designing DNA with GANs

GAN (left) can generate “designs” that lay well over the known data, but expand the space of what is known with knew DNA sequence candidates (right)

Killoran, Lee, Delong, Duvenaud, Frey, 2017

Page 40: Neural Network Approaches for Reducing Healthcare Costs · 2019-06-21 · Neural Network Approaches for Reducing Healthcare Costs Kimberly Robasky Translational Research Scientist,

Can a Neural Net teach us what it learned?

Page 41: Neural Network Approaches for Reducing Healthcare Costs · 2019-06-21 · Neural Network Approaches for Reducing Healthcare Costs Kimberly Robasky Translational Research Scientist,

Example of Self-Explaining NN: DCell

Ma, Nature Methods, 2018

Dcell’s Neural Network architecture mimics the known hierarchical organization of the data and the perceptronshelp to explain the results.

Page 42: Neural Network Approaches for Reducing Healthcare Costs · 2019-06-21 · Neural Network Approaches for Reducing Healthcare Costs Kimberly Robasky Translational Research Scientist,

Review

Promise of Precision Medicine

Challenge of Clinical Trials

Burdens and Blessings of Genomic Data

Reducing Healthcare Costs with Emerging Technologies

Page 43: Neural Network Approaches for Reducing Healthcare Costs · 2019-06-21 · Neural Network Approaches for Reducing Healthcare Costs Kimberly Robasky Translational Research Scientist,

Take-aways

Promise of Precision Medicine

Right drug, right patient, right timeChallenge of Clinical Trials:

Costly, time consuming, failures – need biomarkersBurdens and Blessings of Genomic Data

New biomarkers, but so much data!Reducing Healthcare Costs with Emerging Technologies:

GANs can learn genomic data distributions,

Make them report back findings

Page 44: Neural Network Approaches for Reducing Healthcare Costs · 2019-06-21 · Neural Network Approaches for Reducing Healthcare Costs Kimberly Robasky Translational Research Scientist,

Next steps: How can you help?

1. Learn oneDevelop knowledge about Analytical and Visualization tools

GANS original source: Goodfellow, 2014Neural Networks: Coursera Applied Bioinformatics: SILS 890-259 (contact me for pre-requisites)

Practice the languagePython/R courses: Solo Learn, Data Camp

2. Do oneInternship/Practicum

3. Teach oneFor RENCI, Contact me – be patient, but be [email protected]


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