Using Topological Data Analysis to Study Glandular Architecture - - PowerPoint PPT Presentation

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Using Topological Data Analysis to Study Glandular Architecture - - PowerPoint PPT Presentation

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Using Topological Data Analysis to Study Glandular Architecture Brittany Terese Fasy School of Computing, Montana State University 2 October 2016 TDA-Bio Workshop Seattle, Washington B. Fasy (MSU) TDA for Glandular Architecture 2 October

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SLIDE 1

Using Topological Data Analysis to Study Glandular Architecture

Brittany Terese Fasy

School of Computing, Montana State University

2 October 2016 TDA-Bio Workshop Seattle, Washington

  • B. Fasy (MSU)

TDA for Glandular Architecture 2 October 2016 1 / 22

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SLIDE 2

Joint Work With

Carola Wenk (Tulane, CS)

  • J. Quincy Brown (Tulane, BME)

0NSF DMS / NIH Planning Grant: 1557716 (MSU) and 1557750 (Tulane)

  • B. Fasy (MSU)

TDA for Glandular Architecture 2 October 2016 2 / 22

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SLIDE 3

Joint Work With

Carola Wenk (Tulane, CS)

  • J. Quincy Brown (Tulane, BME)

Andrew Sholl (Tulane Med) John Sheppard (MSU, CS) Brian Summa (Tulane, CS)

0NSF DMS / NIH Planning Grant: 1557716 (MSU) and 1557750 (Tulane)

  • B. Fasy (MSU)

TDA for Glandular Architecture 2 October 2016 2 / 22

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SLIDE 4

Joint Work With

Carola Wenk (Tulane, CS)

  • J. Quincy Brown (Tulane, BME)

Andrew Sholl (Tulane Med) John Sheppard (MSU, CS) Brian Summa (Tulane, CS) Pete Lawson (Tulane, BME) Eric Berry (MSU, Math) Sush Majhi (Tulane, Math) Alan Cleary (MSU, CS) Sawyer Payne(MSU, CS Undergrad)

0NSF DMS / NIH Planning Grant: 1557716 (MSU) and 1557750 (Tulane)

  • B. Fasy (MSU)

TDA for Glandular Architecture 2 October 2016 2 / 22

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SLIDE 5

The Problem: Qualitative Diagnosis and Prognosis

Prostate Cancer

The Question is Will He Outlive It?

More than 225, 000 cases per year (USA). One is seven men will be diagnosed. Treatments: surgery, chemo, radiation, harmone therapy. Either slowly-growing and benign or fast-growing and dangerous. Surgery / radiation benefits questionable for SG/B. Surgery / radiation side effects not desirable. ... therefore, active surveillance.

  • B. Fasy (MSU)

TDA for Glandular Architecture 2 October 2016 3 / 22

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SLIDE 6

The Problem: Qualitative Diagnosis and Prognosis

Prostate Cancer

Diagnosis

PCA

  • B. Fasy (MSU)

TDA for Glandular Architecture 2 October 2016 4 / 22

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SLIDE 7

The Problem: Qualitative Diagnosis and Prognosis

Prostate Cancer

Diagnosis

4+3 3+4 3+3 2+2 4+4 5+4 5+5 Radical Surveillance PCA

  • B. Fasy (MSU)

TDA for Glandular Architecture 2 October 2016 4 / 22

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SLIDE 8

The Problem: Qualitative Diagnosis and Prognosis

Prostate Cancer

Diagnosis

4+3 3+4 3+3 2+2 4+4 5+4 5+5 4+3 3+4 3+3 2+2 4+4 5+4 5+5 Radical Surveillance PCA

  • B. Fasy (MSU)

TDA for Glandular Architecture 2 October 2016 4 / 22

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SLIDE 9

The Problem: Qualitative Diagnosis and Prognosis

Prostate Cancer

Diagnosis

PCA Age S.M. Other Treatment 4+3 3+4 3+3 2+2 4+4 5+4 5+5 4+3 3+4 3+3 2+2 4+4 5+4 5+5 Radical Surveillance PCA

  • B. Fasy (MSU)

TDA for Glandular Architecture 2 October 2016 4 / 22

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SLIDE 10

The Problem: Qualitative Diagnosis and Prognosis

Biopsy and Prostectmy Slides

How to Describe Glandular Architecture

  • B. Fasy (MSU)

TDA for Glandular Architecture 2 October 2016 5 / 22

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SLIDE 11

The Problem: Qualitative Diagnosis and Prognosis

Gleason Grading

Grade 1: well-defined, nicely packed Grade 2: larger, more tissue, less uniform Grade 3: less defined glands, some cribriform Grade 4: fused glands, open lumens Grade 5: no glandular definition, sheets of cells

0Donald Gleason, 1966, image from The Gleason Grading System: A Complete Guide

for Pathologist and Clinicians by Eppstein

  • B. Fasy (MSU)

TDA for Glandular Architecture 2 October 2016 6 / 22

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SLIDE 12

The Problem: Qualitative Diagnosis and Prognosis

Gleason Grading

Grade 1: well-defined, nicely packed Grade 2: larger, more tissue, less uniform Grade 3: less defined glands Grade 4: fused glands, open lumens, cribriform Grade 5: no glandular definition, sheets of cells

02005 Consensus, image from The Gleason Grading System: A Complete Guide for

Pathologist and Clinicians by Eppstein

  • B. Fasy (MSU)

TDA for Glandular Architecture 2 October 2016 6 / 22

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SLIDE 13

The Problem: Qualitative Diagnosis and Prognosis

Learning to Grade

The Gleason Grading System: A Complete Guide for Pathologists and Clinicians

  • B. Fasy (MSU)

TDA for Glandular Architecture 2 October 2016 7 / 22

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SLIDE 14

The Problem: Qualitative Diagnosis and Prognosis

Glandular Architecture

Discrete-vs-Fused Glands

Gleason 3 Discrete glands. Gleason 4 Presence of fused glands.

0Image source: Eppstein, The Gleason Grading System

  • B. Fasy (MSU)

TDA for Glandular Architecture 2 October 2016 8 / 22

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SLIDE 15

The Problem: Qualitative Diagnosis and Prognosis

Glandular Architecture

Cribriform Pattern

Gleason 4 A gland with numerous small holes.

0Image source: Eppstein, The Gleason Grading System

  • B. Fasy (MSU)

TDA for Glandular Architecture 2 October 2016 9 / 22

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SLIDE 16

The Problem: Qualitative Diagnosis and Prognosis

Glandular Architecture

Glomeruloid Structures

Gleason 3,4 Intraluminal cribriform, single point of attachment.

0Image source:

http://www.nature.com/modpathol/journal/v17/n3/fig_tab/3800050f9.html

  • B. Fasy (MSU)

TDA for Glandular Architecture 2 October 2016 10 / 22

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SLIDE 17

The Problem: Qualitative Diagnosis and Prognosis

Glandular Architecture

Telescoping Glands

Gleason 3 Telescoping (gland in gland) may mimic Glumeroid. Gleason 4 Actual glumeroid pattern.

0Image source: Eppstein, The Gleason Grading System

  • B. Fasy (MSU)

TDA for Glandular Architecture 2 October 2016 11 / 22

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SLIDE 18

The Problem: Qualitative Diagnosis and Prognosis

Glandular Architecture

Distribution of Glandular Shape and Size

Gleason 1 Uniform distribution of gland

  • size. Round.

Gleason 3 Irregularly separated glands. Gleason 4 Poorly formed glands.

0Image source: Eppstein, The Gleason Grading System

  • B. Fasy (MSU)

TDA for Glandular Architecture 2 October 2016 12 / 22

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SLIDE 19

Methods: TDA

Persistent Homology

?

=

  • B. Fasy (MSU)

TDA for Glandular Architecture 2 October 2016 13 / 22

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SLIDE 20

Methods: TDA

Persistent Homology

?

=

  • B. Fasy (MSU)

TDA for Glandular Architecture 2 October 2016 13 / 22

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SLIDE 21

Methods: TDA

Quantifying the Process

TDA

  • B. Fasy (MSU)

TDA for Glandular Architecture 2 October 2016 14 / 22

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SLIDE 22

Methods: TDA

Quantifying the Process

TDA

  • B. Fasy (MSU)

TDA for Glandular Architecture 2 October 2016 14 / 22

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SLIDE 23

Methods: TDA

Quantifying the Process

TDA

  • B. Fasy (MSU)

TDA for Glandular Architecture 2 October 2016 14 / 22

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SLIDE 24

Methods: TDA

Quantifying the Process

TDA

Birth Death

  • B. Fasy (MSU)

TDA for Glandular Architecture 2 October 2016 14 / 22

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SLIDE 25

Methods: TDA

Quantifying the Process

TDA

Birth Death

  • B. Fasy (MSU)

TDA for Glandular Architecture 2 October 2016 14 / 22

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SLIDE 26

Methods: TDA

Quantifying the Process

TDA

Birth Death

Birth Death

  • B. Fasy (MSU)

TDA for Glandular Architecture 2 October 2016 14 / 22

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SLIDE 27

Methods: TDA

Quantifying the Process

TDA

Birth Death

Birth Death (Birth + Death)/2

20 40 60 80 100 120

  • B. Fasy (MSU)

TDA for Glandular Architecture 2 October 2016 14 / 22

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SLIDE 28

Methods: TDA

Functional and Vectorized Summaries

Birth Death

(Birth + Death)/2

20 40 60 80 100 120

  • B. Fasy (MSU)

TDA for Glandular Architecture 2 October 2016 15 / 22

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SLIDE 29

Methods: TDA

Aside: Hypothesis Testing

Upcoming Paper The Euler Characteristic curve seems to be the most discriminating among the functional summaries when using the Hotelling Testa.

aJoint work with Jessi Cisewski, Wojciech Hellwing, Mark Lovell, Alessandro

Rinaldo, Larry Wasserman, Mike Wu

  • B. Fasy (MSU)

TDA for Glandular Architecture 2 October 2016 16 / 22

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SLIDE 30

Methods: TDA

Collaboration

  • B. Fasy (MSU)

TDA for Glandular Architecture 2 October 2016 17 / 22

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SLIDE 31

Results: Towards Classification

Comparing Purely Graded Images

Initial Results

4 4 4 4 4 3 3 3 3 3 3 3 4 4 4 5 5 5 5 5 5 55 3 3 3 3 4 4 44 4

−9 −6 −3 −20 −15 −10 −5 5

  • B. Fasy (MSU)

TDA for Glandular Architecture 2 October 2016 18 / 22

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SLIDE 32

Other Problems:

Analyzing DeBruijn Graphs

Joint work with Alan Cleary and Brendan Mumey

CTGAACAGCTAGCAGTAGTGTAGGG

  • B. Fasy (MSU)

TDA for Glandular Architecture 2 October 2016 19 / 22

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SLIDE 33

Other Problems:

Analyzing DeBruijn Graphs

Joint work with Alan Cleary and Brendan Mumey

CTGAACAGCTAGCAGTAGTGTAGGG CTG TGA GAA AAC CAG AGC GCT CTA TAG GCA AGT GTA TAT GTG AGG GGG

  • B. Fasy (MSU)

TDA for Glandular Architecture 2 October 2016 19 / 22

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SLIDE 34

Other Problems:

Analyzing DeBruijn Graphs

Joint work with Alan Cleary and Brendan Mumey

CTGAACAGCTAGCAGTAGTGTAGGG CTG TGA GAA AAC CAG AGC GCT CTA TAG GCA AGT GTA TAT GTG AGG GGG

  • B. Fasy (MSU)

TDA for Glandular Architecture 2 October 2016 19 / 22

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SLIDE 35

Other Problems:

Analyzing DeBruijn Graphs

Joint work with Alan Cleary and Brendan Mumey

CTGAACAGCTAGCAGTAGTGTAGGG CTG TGA GAA AAC CAG AGC GCT CTA TAG GCA AGT GTA TAT GTG AGG GGG

  • B. Fasy (MSU)

TDA for Glandular Architecture 2 October 2016 19 / 22

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SLIDE 36

Other Problems:

Analyzing DeBruijn Graphs

Joint work with Alan Cleary and Brendan Mumey

CTGAACAGCTAGCAGTAGTGTAGGG CTG TGA GAA AAC CAG AGC GCT CTA TAG GCA AGT GTA TAT GTG AGG GGG

  • B. Fasy (MSU)

TDA for Glandular Architecture 2 October 2016 19 / 22

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SLIDE 37

Other Problems:

Analyzing DeBruijn Graphs

Joint work with Alan Cleary and Brendan Mumey

CTGAACAGCTAGCAGTAGTGTAGGG CTG TGA GAA AAC CAG AGC GCT CTA TAG GCA AGT GTA TAT GTG AGG GGG

  • B. Fasy (MSU)

TDA for Glandular Architecture 2 October 2016 19 / 22

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SLIDE 38

Other Problems:

Analyzing DeBruijn Graphs

Joint work with Alan Cleary and Brendan Mumey

CTGAACAGCTAGCAGTAGTGTAGGG CTG TGA GAA AAC CAG AGC GCT CTA TAG GCA AGT GTA TAT GTG AGG GGG

  • B. Fasy (MSU)

TDA for Glandular Architecture 2 October 2016 19 / 22

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SLIDE 39

Other Problems:

Analyzing DeBruijn Graphs

Joint work with Alan Cleary and Brendan Mumey

CTGAACAGCTAGCAGTAGTGTAGGG CTG TGA GAA AAC CAG AGC GCT CTA TAG GCA AGT GTA TAT GTG AGG GGG

  • B. Fasy (MSU)

TDA for Glandular Architecture 2 October 2016 19 / 22

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SLIDE 40

Other Problems:

Analyzing DeBruijn Graphs

Joint work with Alan Cleary and Brendan Mumey

CTGAACAGCTAGCAGTAGTGTAGGG CTG TGA GAA AAC CAG AGC GCT CTA TAG GCA AGT GTA TAT GTG AGG GGG

  • B. Fasy (MSU)

TDA for Glandular Architecture 2 October 2016 19 / 22

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SLIDE 41

Other Problems:

Analyzing DeBruijn Graphs

Joint work with Alan Cleary and Brendan Mumey

CTGAACAGCTAGCAGTAGTGTAGGG CTG TGA GAA AAC CAG AGC GCT CTA TAG GCA AGT GTA TAT GTG AGG GGG

  • B. Fasy (MSU)

TDA for Glandular Architecture 2 October 2016 19 / 22

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SLIDE 42

Other Problems:

Analyzing DeBruijn Graphs

Joint work with Alan Cleary and Brendan Mumey

CTGAACAGCTAGCAGTAGTGTAGGG CTG TGA GAA AAC CAG AGC GCT CTA TAG GCA AGT GTA TAT GTG AGG GGG

  • B. Fasy (MSU)

TDA for Glandular Architecture 2 October 2016 19 / 22

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SLIDE 43

Other Problems:

Analyzing DeBruijn Graphs

Joint work with Alan Cleary and Brendan Mumey

CTGAACAGCTAGCAGTAGTGTAGGG CTG TGA GAA AAC CAG AGC GCT CTA TAG GCA AGT GTA TAT GTG AGG GGG

  • B. Fasy (MSU)

TDA for Glandular Architecture 2 October 2016 19 / 22

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SLIDE 44

Other Problems:

Analyzing DeBruijn Graphs

Joint work with Alan Cleary and Brendan Mumey

CTGAACAGCTAGCAGTAGTGTAGGG CTG TGA GAA AAC CAG AGC GCT CTA TAG GCA AGT GTA TAT GTG AGG GGG

  • B. Fasy (MSU)

TDA for Glandular Architecture 2 October 2016 19 / 22

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SLIDE 45

Other Problems:

Analyzing DeBruijn Graphs

Joint work with Alan Cleary and Brendan Mumey

CTGAACAGCTAGCAGTAGTGTAGGG CTG TGA GAA AAC CAG AGC GCT CTA TAG GCA AGT GTA TAT GTG AGG GGG

  • B. Fasy (MSU)

TDA for Glandular Architecture 2 October 2016 19 / 22

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SLIDE 46

Other Problems:

Analyzing DeBruijn Graphs

Joint work with Alan Cleary and Brendan Mumey

CTGAACAGCTAGCAGTAGTGTAGGG CTG TGA GAA AAC CAG AGC GCT CTA TAG GCA AGT GTA TAT GTG AGG GGG

  • B. Fasy (MSU)

TDA for Glandular Architecture 2 October 2016 19 / 22

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SLIDE 47

Other Problems:

Analyzing DeBruijn Graphs

Joint work with Alan Cleary and Brendan Mumey

CTGAACAGCTAGCAGTAGTGTAGGG CTG TGA GAA AAC CAG AGC GCT CTA TAG GCA AGT GTA TAT GTG AGG GGG

  • B. Fasy (MSU)

TDA for Glandular Architecture 2 October 2016 19 / 22

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SLIDE 48

Other Problems:

Analyzing DeBruijn Graphs

Joint work with Alan Cleary and Brendan Mumey

CTGAACAGCTAGCAGTAGTGTAGGG CTG TGA GAA AAC CAG AGC GCT CTA TAG GCA AGT GTA TAT GTG AGG GGG

  • B. Fasy (MSU)

TDA for Glandular Architecture 2 October 2016 19 / 22

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SLIDE 49

Other Problems:

Analyzing DeBruijn Graphs

Joint work with Alan Cleary and Brendan Mumey

CTGAACAGCTAGCAGTAGTGTAGGG CTG TGA GAA AAC CAG AGC GCT CTA TAG GCA AGT GTA TAT GTG AGG GGG

  • B. Fasy (MSU)

TDA for Glandular Architecture 2 October 2016 19 / 22

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SLIDE 50

Other Problems:

Analyzing DeBruijn Graphs

Joint work with Alan Cleary and Brendan Mumey

CTGAACAGCTAGCAGTAGTGTAGGG CTG TGA GAA AAC CAG AGC GCT CTA TAG GCA AGT GTA TAT GTG AGG GGG

  • B. Fasy (MSU)

TDA for Glandular Architecture 2 October 2016 19 / 22

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SLIDE 51

Other Problems:

Analyzing DeBruijn Graphs

Joint work with Alan Cleary and Brendan Mumey

CTGAACAGCTAGCAGTAGTGTAGGG CTG TGA GAA AAC CAG AGC GCT CTA TAG GCA AGT GTA TAT GTG AGG GGG

  • B. Fasy (MSU)

TDA for Glandular Architecture 2 October 2016 19 / 22

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SLIDE 52

Other Problems:

Bubbles in DeBruijn Graphs

0Nature article: De Novo Assembly and Genotyping of Variants using Colored De

Bruijn Graphs by Iqbal, Caccamo, Turner, Flicek, McVean

  • B. Fasy (MSU)

TDA for Glandular Architecture 2 October 2016 20 / 22

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SLIDE 53

Other Problems:

Bubbles in DeBruijn Graphs

0Nature article: De Novo Assembly and Genotyping of Variants using Colored De

Bruijn Graphs by Iqbal, Caccamo, Turner, Flicek, McVean

  • B. Fasy (MSU)

TDA for Glandular Architecture 2 October 2016 20 / 22

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SLIDE 54

Other Problems:

Bubbles in DeBruijn Graphs

0Nature article: De Novo Assembly and Genotyping of Variants using Colored De

Bruijn Graphs by Iqbal, Caccamo, Turner, Flicek, McVean

  • B. Fasy (MSU)

TDA for Glandular Architecture 2 October 2016 20 / 22

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SLIDE 55

Other Problems:

Bubbles in DeBruijn Graphs

0Nature article: De Novo Assembly and Genotyping of Variants using Colored De

Bruijn Graphs by Iqbal, Caccamo, Turner, Flicek, McVean

  • B. Fasy (MSU)

TDA for Glandular Architecture 2 October 2016 20 / 22

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SLIDE 56

Other Problems:

TDA R Package

Maintained by Fasy, Kim, and Maria

Front-end to various TDA libraries Plotting Diagrams Landscapes, Silhouettes Statistical Techniques (including confidence sets) (Soon) Intensity Plots

  • B. Fasy (MSU)

TDA for Glandular Architecture 2 October 2016 21 / 22

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SLIDE 57

Other Problems:

Thank You!

Contact: brittany@fasy.us

  • B. Fasy (MSU)

TDA for Glandular Architecture 2 October 2016 22 / 22