Thesis/presentation.mkdn

% Bioinformatic analysis of complex, high-throughput genomic and epigenomic data in the context of $\mathsf{CD4}^{+}$ T-cell differentiation and diagnosis and treatment of transplant rejection
% Ryan C. Thompson \
  Su Lab \
  The Scripps Research Institute
% October 24, 2019

# Intro

# Biological motivation: Transplant rejection

## Organ transplants are a life-saving treatment for many

\Large

* 36,528 transplants performed in the USA in 2018[^1]

. . .

* 100 transplants every day!

. . .

* Over 113,000 people on the national transplant waiting list as of
  July 2019

[^1]: Source: https://www.organdonor.gov/statistics-stories/statistics.html

## Organ transplants are a life-saving treatment for many

![Organ donation statistics for the USA in 2018[^2]](graphics/presentation/transplants-organ-CROP.pdf){ height=70% }

[^2]: Source: https://www.organdonor.gov/statistics-stories/statistics.html

## Rejection is an adaptive immune response against a graft

* The host's adaptive immune system identifies and attacks cells
  bearing non-self antigens

. . .

* An allograft contains differnet genetic variants from the host,
  resulting in protein-coding differences

. . .

* Left unchecked, the host immune system eventually notices these
  alloantigens and begins attacking (rejecting) the graft

. . .

\Large

* Rejection is the major long-term threat to organ allografts

## Allograft rejection remains a major long-term problem

![Kidney allograft survival rates in children by transplant year[^3]](graphics/presentation/kidney-graft-survival.png){ height=65% }

[^3]: Kim & Marks. "Long-term outcomes of children after solid organ transplantation". In: Clinics (2014)

## Rejection is treated with immune suppressive drugs

* To prevent rejection, a graft recipient must take immune suppressive
  drugs for the rest of their life

* The graft is periodically checked for signs of rejection, and immune
  suppression dosage is adjusted accordingly

* Immune suppression is a delicate balance: too much leads to immune
  compromise; too little leads to rejection.

. . .

* Both diagnosis and treatment present significant challenges

* Immune memory is a major confounder

## My thesis topics

### Chapter 2
Genome-wide epigenetic analysis of H3K4 and H3K27 methylation in naïve
and memory $\mathsf{CD4}^{+}$ T-cell activation

### Chapter 3
Improving array-based diagnostics for transplant rejection by
optimizing data preprocessing

### Chapter 4
Globin-blocking for more effective blood RNA-seq analysis in primate
animal model for experimental graft rejection treatment

## Today's focus

### Chapter 2

\Large

Genome-wide epigenetic analysis of H3K4 and H3K27 methylation in naïve
and memory $\mathsf{CD4}^{+}$ T-cell activation

## Memory cells: faster, stronger, and more independent

![Memory T-cells proliferate and respond more quickly](graphics/presentation/T-cells-SVG.pdf)

## Immune memory is a significant contributor to rejection

![Memory T-cells proliferate and respond more quickly](graphics/presentation/T-cells-SVG.pdf)

# Figure Storage

## Slides
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