Merge branch 'slides'

.gitignore

@@ -21,3 +21,5 @@
 tmp-*
 *-PROCESSED.*
 *-final.lyx
+*ROT[0-9]*.png
+*SVG.png

Snakefile

@@ -1,11 +1,13 @@
 # -*- coding: utf-8; -*-
 
 import locale
+import os
 import os.path
 import regex
 import urllib.parse
 import os.path
 import bibtexparser
+import pypandoc
 
 from collections.abc import Iterable, Mapping
 from distutils.spawn import find_executable
@@ -13,6 +15,10 @@ from fnmatch import fnmatch
 from subprocess import check_output, check_call
 from tempfile import NamedTemporaryFile
 from bibtexparser.bibdatabase import BibDatabase
+from lxml import html
+from snakemake.utils import min_version
+
+min_version('3.7.1')
 
 try:
     from os import scandir, walk
@@ -62,10 +68,10 @@ def find_mac_app(name):
         result = \
             check_output_decode(
                 ['mdfind',
-                'kMDItemDisplayName=={name}.app&&kMDItemKind==Application'.format(name=name)]).split('\n')[0] or \
+                'kMDItemDisplayName=="{name}.app"c&&kMDItemKind==Application'.format(name=name)]).split('\n')[0] or \
             check_output_decode(
                 ['mdfind',
-                 'kMDItemDisplayName=={name}&&kMDItemKind==Application'.format(name=name)]).split('\n')[0]
+                 'kMDItemDisplayName=="{name}"c&&kMDItemKind==Application'.format(name=name)]).split('\n')[0]
         if result:
             return result
         else:
@@ -73,30 +79,35 @@ def find_mac_app(name):
     except Exception:
         return None
 
-def find_lyx():
-    lyx_finders = [
-        lambda: find_executable('lyx'),
-        lambda: os.path.join(find_mac_app('LyX'), 'Contents/MacOS/lyx'),
-        lambda: '/Applications/Lyx.app/Contents/MacOS/lyx',
-    ]
-    for finder in lyx_finders:
-        try:
-            lyxpath = finder()
-            if not lyxpath:
-                continue
-            elif not os.access(lyxpath, os.X_OK):
-                continue
-            else:
-                return lyxpath
-        except Exception:
-            pass
+def find_executable_on_mac(executable, path=None, app_name=None, app_paths=None):
+    # Easy case
+    found_executable = find_executable(executable, path)
+    if found_executable:
+        return found_executable
+    # Ok, now we search
+    if app_paths is None:
+        app_paths = []
+    if app_name is None:
+        app_name = executable
+    found_app_path = find_mac_app(app_name)
+    if found_app_path:
+        app_paths.append(found_app_path)
+    if app_paths:
+        new_search_path = ":".join(os.path.join(p, 'Contents/MacOS') for p in app_paths)
+        return find_executable(executable, path=new_search_path)
     else:
-        # Fallback which will just trigger an error when run
-        return '/bin/false'
+        return None
 
-LYX_PATH = find_lyx()
+# Fallback to /bin/false to trigger an error when run (we don't want
+# to trigger an error now, while building the rules)
+LYX_PATH = find_executable_on_mac('lyx') or '/bin/false'
+# GIMP_PATH = find_executable_on_mac('gimp', app_name='gimp*') or '/bin/false'
 PDFINFO_PATH = find_executable('pdfinfo')
 
+def print_pdfinfo(filename):
+    if PDFINFO_PATH:
+        shell('''{PDFINFO_PATH} {filename:q}''')
+
 def glob_recursive(pattern, top='.', include_hidden=False, *args, **kwargs):
     '''Combination of glob.glob and os.walk.
 
@@ -201,28 +212,38 @@ def tex_gfx_extensions(tex_format = 'xetex'):
     except FileNotFoundError:
         return ()
 
+def get_latex_included_gfx(fname):
+    '''Return list of all graphics included from '''
+    try:
+        with open(fname) as infile:
+            beamer_latex = infile.read()
+        # Remove comments
+        beamer_latex = regex.sub('^%.*$','', beamer_latex)
+        # Find graphics included
+        return [ m.group(1) for m in regex.finditer(r'\includegraphics(?:\[.*?\])?\{(.+?)\}', beamer_latex) ]
+    except FileNotFoundError:
+        return ()
+
 rsync_common_args = ['-rL', '--size-only', '--delete', '--exclude', '.DS_Store', '--delete-excluded',]
 
 rule build_all:
-    input: 'thesis.pdf', 'thesis-final.pdf'
+    input: 'thesis.pdf', 'thesis-final.pdf', 'presentation.pdf'
 
 # Note: Any rule that generates an input LyX file for this rule must
 # be marked as a checkpoint. See
 # https://snakemake.readthedocs.io/en/stable/snakefiles/rules.html#data-dependent-conditional-execution
-rule lyx_to_pdf:
+rule thesis_lyx_to_pdf:
     '''Produce PDF output for a LyX file.'''
     input: lyxfile = '{basename}.lyx',
            gfx_deps = lambda wildcards: lyx_gfx_deps(wildcards.basename + '.lyx'),
            bib_deps = lambda wildcards: lyx_bib_deps(wildcards.basename + '.lyx'),
            tex_deps = lambda wildcards: lyx_input_deps(wildcards.basename + '.lyx'),
-    # This rule doesn't produce the PDFs in graphics/
-    output: pdf='{basename,(?!graphics/).*}.pdf'
+    output: pdf='{basename,thesis.*}.pdf'
     run:
         if not LYX_PATH or LYX_PATH == '/bin/false':
             raise Exception('Path to LyX  executable could not be found.')
         shell('''{LYX_PATH:q} -batch --verbose --export-to pdf4 {output.pdf:q} {input.lyxfile:q}''')
-        if PDFINFO_PATH:
-            shell('''{PDFINFO_PATH} {output.pdf:q}''')
+        print_pdfinfo(output.pdf)
 
 checkpoint lyx_add_final:
     '''Copy LyX file and add final option.'''
@@ -292,10 +313,20 @@ rule pdf_crop:
     shell: 'pdfcrop --resolution 300 {input:q} {output:q}'
 
 rule pdf_raster:
-    '''Rasterize PDF to PNG at 600 PPI.'''
+    '''Rasterize PDF to PNG at 600 PPI.
+
+    The largest dimension is scaled '''
     input: pdf = 'graphics/{basename}.pdf'
     output: png = 'graphics/{basename}-RASTER.png'
-    shell: 'pdftoppm -r 600 {input:q} | convert - {output:q}'
+    shell: 'pdftoppm -singlefile -r 600 {input:q} | convert - {output:q}'
+
+rule pdf_raster_res:
+    '''Rasterize PDF to PNG at specific PPI.
+
+    The largest dimension is scaled '''
+    input: pdf = 'graphics/{basename}.pdf'
+    output: png = 'graphics/{basename}-RASTER{res,[1-9][0-9]+}.png'
+    shell: 'pdftoppm -singlefile -r {wildcards.res} {input:q} | convert - {output:q}'
 
 rule png_crop:
     '''Crop away empty margins from a PNG.'''
@@ -303,13 +334,91 @@ rule png_crop:
     output: pdf = 'graphics/{basename,.*(?<!-CROP)}-CROP.png'
     shell: 'convert {input:q} -trim {output:q}'
 
+rule jpg_crop:
+    '''Crop away empty margins from a JPG.'''
+    input: pdf = 'graphics/{basename}.jpg'
+    output: pdf = 'graphics/{basename,.*(?<!-CROP)}-CROP.jpg'
+    shell: 'convert {input:q} -trim {output:q}'
+
 rule svg_to_pdf:
     input: 'graphics/{filename}.svg'
     output: 'graphics/{filename}-SVG.pdf'
-    shell: '''inkscape {input:q} --export-pdf={output:q} --export-dpi=300'''
+    run:
+        infile = os.path.join(os.path.abspath("."), input[0])
+        outfile = os.path.join(os.path.abspath("."), output[0])
+        shell('''inkscape {infile:q} --export-pdf={outfile:q} --export-dpi=300''')
+
+rule svg_raster:
+    input: 'graphics/{filename}.svg'
+    output: 'graphics/{filename}-SVG.png'
+    run:
+        infile = os.path.join(os.path.abspath("."), input[0])
+        outfile = os.path.join(os.path.abspath("."), output[0])
+        shell('''inkscape {infile:q} --export-png={outfile:q} --export-dpi=300''')
+
+rule png_rotate:
+    input: 'graphics/{filename}.png'
+    output: 'graphics/{filename}-ROT{angle,[1-9][0-9]*}.png'
+    run:
+        if re.search('-ROT[1-9][0-9]*$', wildcards.filename):
+            raise ValueError("Cannot double-rotate")
+        shell('convert {input:q} -rotate {wildcards.angle:q} {output:q}')
+
+# rule xcf_to_png:
+#     input: 'graphics/{filename}.xcf'
+#     output: 'graphics/{filename}.png'
+#     shell: 'convert {input:q} -flatten {output:q}'
 
 rule R_to_html:
     '''Render an R script as syntax-hilighted HTML.'''
     input: '{dirname}/{basename}.R'
     output: '{dirname}/{basename,[^/]+}.R.html'
     shell: 'pygmentize -f html -O full -l R -o {output:q} {input:q}'
+
+checkpoint build_beamer_latex:
+    input:
+        extra_preamble='extra-preamble.latex',
+        mkdn_file='{basename}.mkdn',
+        # images=lambda wildcards: get_mkdn_included_images('{basename}.mkdn'.format(**wildcards)),
+        # pdfs=lambda wildcards: get_mkdn_included_pdfs('{basename}.mkdn'.format(**wildcards)),
+    output:
+        latex='{basename,presentation.*}.tex',
+    # TODO: should work with shadow minimal but doesn't
+    run:
+        beamer_latex = pypandoc.convert_file(
+            input.mkdn_file, 'beamer', format='md',
+            extra_args = [
+                '-H', input.extra_preamble,
+                '--pdf-engine=xelatex',
+            ])
+        # Center all columns vertically
+        beamer_latex = beamer_latex.replace(r'\begin{columns}[T]', r'\begin{columns}[c]')
+        with open(output.latex, 'w') as latex_output:
+            latex_output.write(beamer_latex)
+
+rule build_beamer_pdf:
+    input:
+        latex='{basename}.tex',
+        gfx=lambda wildcards: get_latex_included_gfx('{basename}.tex'.format(**wildcards)),
+    output:
+        pdf='{basename,presentation.*}.pdf'
+    shadow: 'minimal'
+    run:
+        shell('''xelatex {input.latex:q} </dev/null''')
+        print_pdfinfo(output.pdf)
+
+rule build_all_presentations:
+    input:
+        'presentation.pdf',
+        'presentation.pptx',
+
+rule make_transplant_organs_graph:
+    input:
+        Rscript='graphics/presentation/transplants-organ.R',
+        data='graphics/presentation/transplants-organ.xlsx',
+    output:
+        pdf='graphics/presentation/transplants-organ.pdf'
+
+    shell: '''
+    Rscript 'graphics/presentation/transplants-organ.R'
+    '''

extra-preamble.latex

@@ -0,0 +1,47 @@
+%% Better graphics sizes
+\usepackage{graphicx}
+% Redefine \includegraphics so that, unless explicit options are
+% given, the image width will not exceed the width or the height of the page.
+% Images get their normal width if they fit onto the page, but
+% are scaled down if they would overflow the margins.
+\makeatletter
+\def\ScaleWidthIfNeeded{%
+ \ifdim\Gin@nat@width>\linewidth
+    \linewidth
+  \else
+    \Gin@nat@width
+  \fi
+}
+\def\ScaleHeightIfNeeded{%
+  \ifdim\Gin@nat@height>0.75\textheight
+    0.75\textheight
+  \else
+    \Gin@nat@width
+  \fi
+}
+\makeatother
+
+\setkeys{Gin}{width=\ScaleWidthIfNeeded,height=\ScaleHeightIfNeeded,keepaspectratio}%
+
+%% Eliminate header
+%%\setbeamertemplate{headline}{}
+
+%% Shorten footer title
+\makeatletter
+\setbeamertemplate{footline}
+{
+  \leavevmode%
+  \hbox{%
+  \begin{beamercolorbox}[wd=.5\paperwidth,ht=2.25ex,dp=1ex,right]{author in head/foot}%
+    \usebeamerfont{author in head/foot}Ryan C. Thompson\hspace*{1em}
+  \end{beamercolorbox}%
+  \begin{beamercolorbox}[wd=.5\paperwidth,ht=2.25ex,dp=1ex,left]{title in head/foot}%
+    \usebeamerfont{title in head/foot}\hspace*{1em}Genomic and epigenomic analysis of $\mathsf{CD4}^{+}$ memory
+  \end{beamercolorbox}}%
+  \vskip0pt%
+}
+\makeatother
+
+%% Eliminate figure numbering
+\usepackage{caption}
+\captionsetup{labelformat=empty,labelsep=none}

graphics/presentation/RCT-thesis-table2.2.svg

@@ -0,0 +1,2171 @@
+<?xml version="1.0" encoding="UTF-8" standalone="no"?>
+<svg
+   xmlns:dc="http://purl.org/dc/elements/1.1/"
+   xmlns:cc="http://creativecommons.org/ns#"
+   xmlns:rdf="http://www.w3.org/1999/02/22-rdf-syntax-ns#"
+   xmlns:svg="http://www.w3.org/2000/svg"
+   xmlns="http://www.w3.org/2000/svg"
+   xmlns:xlink="http://www.w3.org/1999/xlink"
+   xmlns:sodipodi="http://sodipodi.sourceforge.net/DTD/sodipodi-0.dtd"
+   xmlns:inkscape="http://www.inkscape.org/namespaces/inkscape"
+   width="612pt"
+   height="792pt"
+   viewBox="0 0 612 792"
+   version="1.1"
+   id="svg4457"
+   sodipodi:docname="RCT-thesis-table2.2.svg"
+   inkscape:version="0.92.2 5c3e80d, 2017-08-06">
+  <metadata
+     id="metadata4461">
+    <rdf:RDF>
+      <cc:Work
+         rdf:about="">
+        <dc:format>image/svg+xml</dc:format>
+        <dc:type
+           rdf:resource="http://purl.org/dc/dcmitype/StillImage" />
+      </cc:Work>
+    </rdf:RDF>
+  </metadata>
+  <sodipodi:namedview
+     pagecolor="#ffffff"
+     bordercolor="#666666"
+     borderopacity="1"
+     objecttolerance="10"
+     gridtolerance="10"
+     guidetolerance="10"
+     inkscape:pageopacity="0"
+     inkscape:pageshadow="2"
+     inkscape:window-width="1252"
+     inkscape:window-height="744"
+     id="namedview4459"
+     showgrid="false"
+     inkscape:zoom="1.2642212"
+     inkscape:cx="457.92389"
+     inkscape:cy="828.21673"
+     inkscape:window-x="0"
+     inkscape:window-y="0"
+     inkscape:window-maximized="0"
+     inkscape:current-layer="svg4457" />
+  <defs
+     id="defs346">
+    <g
+       id="g344">
+      <symbol
+         overflow="visible"
+         id="glyph0-0">
+        <path
+           style="stroke:none;"
+           d=""
+           id="path2" />
+      </symbol>
+      <symbol
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graphics/presentation/transplants-organ.R

@@ -0,0 +1,26 @@
+#!/usr/bin/env Rscript
+
+library(rctutils)
+library(scriptName)
+library(openxlsx)
+library(forcats)
+library(tidyverse)
+
+tryCatch(
+    setwd(dirname(current_filename())),
+    error=function(...) warning("Could not find script path. Hopefully you are in the right directory already."))
+
+organ_data <- read.xlsx("transplants-organ.xlsx") %>%
+    arrange(desc(Count)) %>%
+    mutate(Organ=fct_inorder(Organ))
+
+p <- ggplot(organ_data) + aes(x=Organ, y=Count, fill=Organ) +
+    geom_col() +
+    geom_text(aes(label=str_c("  ", Organ, " (", Count, ")   "), hjust=ifelse(Count>max(Count)/2, 1, 0)), vjust=0.5) +
+    coord_flip() + scale_x_discrete(limits = rev(levels(organ_data$Organ))) +
+    scale_y_continuous(expand=expand_scale(mult=c(0, 0.01))) +
+    guides(fill=FALSE) +
+    theme(axis.text.y=element_blank(),
+          axis.ticks.y=element_blank()) +
+    ylab("Transplants performed")
+ggprint(p, pdf("transplants-organ.pdf", width=6, height=3))

presentation.mkdn

@@ -0,0 +1,632 @@
+---
+title: 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
+author: |
+    Ryan C. Thompson \
+    Su Lab \
+    The Scripps Research Institute
+date: October 24, 2019
+theme: Boadilla
+aspectratio: 169
+fontsize: 14pt
+---
+
+## Organ transplants are a life-saving treatment
+
+::: incremental
+
+* 36,528 transplants performed in the USA in 2018[^organdonor]
+
+* 100 transplants every day!
+
+* Over 113,000 people on the national transplant waiting list as of
+  July 2019
+
+:::
+
+[^organdonor]: [organdonor.gov](https://www.organdonor.gov/statistics-stories/statistics.html)
+
+## Organ donation statistics for the USA in 2018[^organdonor]
+
+\centering
+
+![](graphics/presentation/transplants-organ-CROP.pdf)
+
+## Types of grafts
+
+A graft is categorized based on the relationship between donor and recipient:
+
+. . .
+
+::: incremental
+
+* **Autograft:** Donor and recipient are the *same individual*
+
+* **Allograft:** Donor and recipient are *different individuals* of
+  the *same species*
+
+* **Xenograft:** Donor and recipient are *different species*
+
+:::
+
+## Recipient T-cells reject allogenic MHCs
+
+:::::::::: {.columns}
+
+::: {.column width="55%"}
+
+:::: incremental
+
+* TCR binds to both antigen *and* MHC surface \vspace{10pt}
+
+* HLA genes encoding MHC proteins are highly polymorphic \vspace{10pt}
+
+* Variants in donor MHC can trigger the same T-cell response as a
+  foreign antigen
+
+::::
+
+:::
+
+::: {.column width="40%"}
+<!-- ![\footnotesize Janeway's Immunobio- logy (2012), Fig. 9.19](graphics/presentation/janeway-fig9.19-TCR.png){ height=70% } -->
+![TCR binding to self (right) and allogenic (left) MHC\footnotemark](graphics/presentation/tcr_mhc.jpg){ height=70% }
+:::
+
+::::::::::
+
+\footnotetext[3]{\href{https://doi.org/10.1016/j.cell.2007.01.048}{Colf, Bankovich, et al. "How a Single T Cell Receptor Recognizes Both Self and Foreign MHC". In: Cell (2007)}}
+
+## Allograft rejection is a major long-term problem
+
+![Kidney allograft survival rates in children by transplant year[^kim-marks]](graphics/presentation/kidney-graft-survival.png){ height=65% }
+
+[^kim-marks]: [Kim & Marks (2014)](https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3884158/?report=classic)
+
+## Rejection is treated with immune suppressive drugs
+
+<!-- TODO: Need a graphic, or maybe a table of common drugs +
+mechanisms, or a diagram for periodic checking. -->
+
+::: incremental
+
+* Graft recipient must take immune suppressive drugs indefinitely
+
+* Graft is monitored for rejection and dosage adjusted over time
+
+* Immune suppression is a delicate balance: too much and too little
+  are both problematic.
+
+:::
+
+## Memory cells: faster, stronger, and more independent
+
+![Naïve T-cell activated by APC](graphics/presentation/T-cells-A-SVG.png)
+
+## Memory cells: faster, stronger, and more independent
+
+![Naïve T-cell differentiates and proliferates into effector T-cells](graphics/presentation/T-cells-B-SVG.png)
+
+## Memory cells: faster, stronger, and more independent
+
+![Post-infection, some effectors cells remain as memory cells](graphics/presentation/T-cells-C-SVG.png)
+
+## Memory cells: faster, stronger, and more independent
+
+![Memory T-cells respond more strongly to activation](graphics/presentation/T-cells-D-SVG.png)
+
+::: notes
+
+Compared to naïve cells, memory cells:
+
+* respond to a lower antigen concentration
+* respond more strongly at any given antigen concentration
+* require less co-stimulation
+* are somewhat independent of some types of co-stimulation required by
+  naïve cells
+* evolve over time to respond even more strongly to their antigen
+
+Result:
+
+* Memory cells require progressively higher doses of immune suppresive
+  drugs
+* Dosage cannot be increased indefinitely without compromising the
+  immune system's ability to fight infection
+
+:::
+
+## 3 problems relating to transplant rejection
+
+### 1. How are memory cells different from naïve?
+
+\onslide<2->{Genome-wide epigenetic analysis of H3K4 and H3K27 methylation in naïve
+and memory $\mathsf{CD4}^{+}$ T-cell activation}
+
+### 2. How can we diagnose rejection noninvasively?
+
+\onslide<3->{Improving array-based diagnostics for transplant rejection by
+optimizing data preprocessing}
+
+### 3. How can we evaluate effects of a rejection treatment?
+
+\onslide<4->{Globin-blocking for more effective blood RNA-seq analysis in primate
+animal model for experimental graft rejection treatment}
+
+## Today's focus
+
+### \Large 1. How are memory cells different from naïve?
+
+\Large
+
+Genome-wide epigenetic analysis of H3K4 and H3K27 methylation in naïve
+and memory $\mathsf{CD4}^{+}$ T-cell activation
+
+## We need a better understanding of immune memory
+
+* Cell surface markers fairly well-characterized
+
+* But internal mechanisms poorly understood
+
+. . .
+
+\vfill
+
+\large
+
+**Hypothesis:** Epigenetic regulation of gene expression through
+histone modification is involved in $\mathsf{CD4}^{+}$ T-cell
+activation and memory.
+  
+## Which histone marks are we looking at?
+
+. . .
+
+::: incremental
+
+* **H3K4me3:** "activating" mark associated with active transcription
+
+* **H3K4me2:** Correlated with H3K4me3, hypothesized "poised" state
+
+* **H3K27me3:** "repressive" mark associated with inactive genes
+
+:::
+
+. . .
+
+\vfill
+
+All involved in T-cell differentiation, but activation dynamics
+unexplored
+
+## ChIP-seq measures DNA bound to marked histones[^chipseq]
+
+\centering
+
+![](graphics/presentation/NRG-chipseq.png){ height=70% }
+
+[^chipseq]: [Furey (2012)](http://www.nature.com/articles/nrg3306)
+
+## Experimental design
+
+\centering
+
+![](graphics/presentation/expdesign-CROP.pdf){ height=70% }
+
+\footnotesize
+
+Data generated by Sarah Lamere, published in GEO as
+[GSE73214](https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE73214)
+
+## Time points capture phases of immune response
+
+\centering
+
+![](graphics/presentation/immune-response.png)
+
+## A few intermediate analysis steps are required
+
+\centering
+
+![](graphics/CD4-csaw/rulegraphs/rulegraph-all-RASTER100.png)
+
+## Questions to focus on
+
+::: incremental
+
+1. How do we define the "promoter region" for each gene? \vspace{10pt}
+2. How do these histone marks behave in promoter regions? \vspace{10pt}
+3. What can these histone marks tell us about T-cell activation and
+   differentiation?
+
+:::
+
+## First question
+
+\centering \LARGE
+
+How do we define the "promoter region" for each gene?
+
+## Histone modifications occur on consecutive histones
+
+![ChIP-seq coverage in IL2 gene[^lamerethesis]](graphics/presentation/LaMere-thesis-fig3.9-SVG-CROP.png){ height=65% }
+
+[^lamerethesis]: Sarah LaMere. Ph.D. thesis (2015).
+
+## Histone modifications occur on consecutive histones
+
+\begin{figure}
+\centering
+\only<1>{\includegraphics[width=\textwidth,height=0.7\textheight]{graphics/presentation/CCF-plots-A-SVG.png}}
+\only<2>{\includegraphics[width=\textwidth,height=0.7\textheight]{graphics/presentation/CCF-plots-B-SVG.png}}
+\only<3>{\includegraphics[width=\textwidth,height=0.7\textheight]{graphics/presentation/CCF-plots-C-SVG.png}}
+\caption{Strand cross-correlation plots show histone-sized wave pattern}
+\end{figure}
+
+## SICER identifies enriched regions across the genome
+
+![Finding "islands" of coverage with SICER[^sicer]](graphics/presentation/SICER-fig1-SVG.png)
+
+[^sicer]: [Zang et al. (2009)](https://doi.org/10.1093/bioinformatics/btp340)
+
+## IDR identifies *reproducible* enriched regions
+
+![Example irreproducible discovery rate[^idr] score consistency plot](graphics/presentation/IDR-example-CROP-RASTER.png){ height=65% }
+
+[^idr]: [Li et al. (2011)](https://doi.org/10.1214/11-AOAS466)
+
+## Finding enriched regions across the genome
+
+![Peak-calling summary statistics](graphics/presentation/RCT-thesis-table2.2-SVG-CROP.png)
+
+## Each histone mark has an "effective promoter radius"
+
+![Enrichment of peaks near promoters](graphics/presentation/Promoter-Peak-Distance-Profile-SVG.pdf)
+
+## Peaks in promoters correlate with gene expression
+
+\begin{figure}
+\centering
+\only<1>{\includegraphics[width=\textwidth,height=0.7\textheight]{graphics/presentation/FPKM-by-Peak-Violin-Plots-A-SVG.png}}
+\only<2>{\includegraphics[width=\textwidth,height=0.7\textheight]{graphics/presentation/FPKM-by-Peak-Violin-Plots-B-SVG.png}}
+\only<3>{\includegraphics[width=\textwidth,height=0.7\textheight]{graphics/presentation/FPKM-by-Peak-Violin-Plots-C-SVG.png}}
+\only<4>{\includegraphics[width=\textwidth,height=0.7\textheight]{graphics/presentation/FPKM-by-Peak-Violin-Plots-D-SVG.png}}
+\only<5>{\includegraphics[width=\textwidth,height=0.7\textheight]{graphics/presentation/FPKM-by-Peak-Violin-Plots-Z-SVG.png}}
+\caption{Expression distributions of genes with and without promoter peaks}
+\end{figure}
+
+## First question
+
+\centering \LARGE
+
+How do we define the "promoter region" for each gene?
+
+## Answer: Define the promoter region empirically!
+
+<!-- TODO: Left column: text; right column: flip through relevant image -->
+
+:::::::::: {.columns}
+::: {.column width="50%"}
+
+* H3K4me2, H3K4me3, and H3K27me3 occur in broad regions across the
+  genome
+* Enriched regions occur more commonly near promoters
+* Each histone mark has its own "effective promoter radius"
+* Presence or absence of a peak within this radius is correlated with
+  gene expression
+
+:::
+
+::: {.column width="50%"}
+\centering
+\only<1>{\includegraphics[width=\textwidth,height=0.7\textheight]{graphics/presentation/CCF-plots-A-SVG.png}}
+\only<2>{\includegraphics[width=\textwidth,height=0.7\textheight]{graphics/presentation/Promoter-Peak-Distance-Profile-SVG.pdf}}
+\only<3>{\includegraphics[width=\textwidth,height=0.7\textheight]{graphics/presentation/FPKM-by-Peak-Violin-Plots-A-SVG.png}}
+:::
+::::::::::
+
+## Next question
+
+\centering \LARGE
+
+How do these histone marks behave in promoter regions?
+
+::: notes
+
+Does the position of a histone modification within a gene promoter
+matter to that gene's expression, or is it merely the presence or
+absence anywhere within the promoter?
+
+:::
+
+## H3K4me2 promoter neighborhood K-means clusters
+
+![Cluster means for H3K4me2](graphics/presentation/H3K4me2-neighborhood-clusters-CROP.png){ height=70% }
+
+## H3K4me2 promoter neighborhood K-means clusters
+
+:::::::::: {.columns}
+::: {.column width="50%"}
+![Cluster means for H3K4me2](graphics/presentation/H3K4me2-neighborhood-clusters-CROP.png){ height=70% }
+:::
+::: {.column width="50%"}
+<!-- This space intentionally left blank -->
+:::
+::::::::::
+
+## H3K4me2 cluster PCA shows a semicircular "fan"
+
+:::::::::: {.columns}
+::: {.column width="50%"}
+![Cluster means for H3K4me2](graphics/presentation/H3K4me2-neighborhood-clusters-CROP.png){ height=70% }
+:::
+::: {.column width="50%"}
+![PCA plot of promoters](graphics/presentation/H3K4me2-neighborhood-PCA-CROP.png){ height=70% }
+:::
+::::::::::
+
+## H3K4me2 near TSS correlates with expression
+
+:::::::::: {.columns}
+::: {.column width="50%"}
+![Cluster means for H3K4me2](graphics/presentation/H3K4me2-neighborhood-clusters-CROP.png){ height=70% }
+:::
+::: {.column width="50%"}
+![Cluster expression distributions](graphics/presentation/H3K4me2-neighborhood-expression-CROP-ROT90.png){ height=70% }
+:::
+::::::::::
+
+## H3K4me3 pattern is similar to H3K4me2
+
+:::::::::: {.columns}
+::: {.column width="50%"}
+![Cluster means for H3K4me3](graphics/presentation/H3K4me3-neighborhood-clusters-CROP.png){ height=70% }
+:::
+::: {.column width="50%"}
+![PCA plot of promoters](graphics/presentation/H3K4me3-neighborhood-PCA-CROP.png){ height=70% }
+:::
+::::::::::
+
+## H3K4me3 pattern is similar to H3K4me2
+
+:::::::::: {.columns}
+::: {.column width="50%"}
+![Cluster means for H3K4me3](graphics/presentation/H3K4me3-neighborhood-clusters-CROP.png){ height=70% }
+:::
+::: {.column width="50%"}
+![Cluster expression distributions](graphics/presentation/H3K4me3-neighborhood-expression-CROP-ROT90.png){ height=70% }
+:::
+::::::::::
+
+## H3K27me3 clusters organize into 3 opposed pairs
+
+:::::::::: {.columns}
+::: {.column width="50%"}
+![Cluster means for H3K27me3](graphics/presentation/H3K27me3-neighborhood-clusters-CROP.png){ height=70% }
+:::
+::: {.column width="50%"}
+![PCA plot of promoters](graphics/presentation/H3K27me3-neighborhood-PCA-CROP.png){ height=70% }
+:::
+::::::::::
+
+## Specific H3K27me3 profiles show elevated expression
+
+:::::::::: {.columns}
+::: {.column width="50%"}
+![Cluster means for H3K27me3](graphics/presentation/H3K27me3-neighborhood-clusters-CROP.png){ height=70% }
+:::
+::: {.column width="50%"}
+![Cluster expression distributions](graphics/presentation/H3K27me3-neighborhood-expression-CROP-ROT90.png){ height=70% }
+:::
+::::::::::
+
+## Current question
+
+\centering \LARGE
+
+How do these histone marks behave in promoter regions?
+
+## Answer: Presence and position both matter!
+
+### H3K4me2 & H3K4me3
+
+* Peak closer to promoter $\Rightarrow$ higher gene expression
+* Slightly asymmetric in favor of peaks downstream of TSS
+
+. . .
+
+### H3K27me3
+
+* Depletion of H3K27me3 at TSS $\Rightarrow$ elevated gene expression
+* Enrichment of H3K27me3 upstream of TSS $\Rightarrow$ *more* elevated
+  expression
+* Other coverage profiles: no association
+
+## Last question
+
+\centering \LARGE
+
+What can these histone marks tell us about T-cell activation and
+differentiation?
+
+## Differential modification disappears by Day 14
+
+![Differential modification between naïve and memory samples at each time point](graphics/presentation/RCT-thesis-table2.4-A-SVG-CROP.pdf)
+
+## Differential modification disappears by Day 14
+
+![Differential modification between naïve and memory samples at each time point](graphics/presentation/RCT-thesis-table2.4-B-SVG-CROP.pdf)
+
+## Promoter H3K4me2 levels converge at Day 14
+
+\centering
+
+![](graphics/CD4-csaw/ChIP-seq/H3K4me2-promoter-PCA-group-CROP.png)
+
+## Promoter H3K4me3 levels converge at Day 14
+
+\centering
+
+![](graphics/CD4-csaw/ChIP-seq/H3K4me3-promoter-PCA-group-CROP.png)
+
+## Promoter H3K27me3 levels converge at Day 14?
+
+\centering
+
+![](graphics/CD4-csaw/ChIP-seq/H3K27me3-promoter-PCA-group-CROP.png)
+
+## Expression converges at Day 14 (in PC 2 & 3)
+
+\centering
+
+![](graphics/CD4-csaw/RNA-seq/PCA-final-23-CROP.png)
+
+## But the data isn't really that clean...
+
+:::::::::: {.columns}
+::: {.column width="50%"}
+![H3K4me2](graphics/CD4-csaw/ChIP-seq/H3K4me2-PCA-raw-CROP.png)
+:::
+::: {.column width="50%"}
+![H3K4me3](graphics/CD4-csaw/ChIP-seq/H3K4me3-PCA-raw-CROP.png)
+:::
+::::::::::
+
+## But the data isn't really that clean...
+
+:::::::::: {.columns}
+::: {.column width="50%"}
+![H3K27me3](graphics/CD4-csaw/ChIP-seq/H3K27me3-PCA-raw-CROP.png)
+:::
+::: {.column width="50%"}
+![RNA-seq](graphics/CD4-csaw/RNA-seq/PCA-no-batchsub-CROP.png)
+:::
+::::::::::
+
+## MOFA: cross-dataset factor analysis
+
+![MOFA factor analysis schematic[^mofa]](graphics/presentation/MOFA-fig1A-SVG.png){ height=70% }
+
+[^mofa]: [Argelaguet, Velten, et. al. (2018)](https://onlinelibrary.wiley.com/doi/abs/10.15252/msb.20178124)
+
+## Some factors are shared while others are not
+
+\centering
+
+![Variance explained in each data set by each LF](graphics/presentation/MOFA-varExplained-matrix-A-CROP.png){ height=70% }
+
+## 3 factors are shared across all 4 data sets
+
+\centering
+
+![LFs 1, 4, and 5 explain variation in all 4 data sets](graphics/presentation/MOFA-varExplained-matrix-B-CROP.png){ height=70% }
+
+## MOFA LF5 captures convergence pattern
+
+![LF1 & LF4: time point effect; LF5: convergence](graphics/presentation/MOFA-LF-scatter-wide.png)
+
+<!-- { height=70% } -->
+
+## Last question
+
+\centering \LARGE
+
+What can these histone marks tell us about T-cell activation and
+differentiation?
+
+## Answer: Epigenetic convergence between naïve and memory!
+
+* Almost no differential histone modification observed between naïve and
+  memory at Day 14, despite plenty of differential modification at
+  earlier time points.
+* Expression and 3 histone marks all show "convergence" between naïve
+  and memory by Day 14 in the first 2 or 3 principal coordinates.
+* MOFA captures this convergence pattern in a single latent factor,
+  indicating that this is a shared pattern across all 4 data sets.
+
+<!-- ## Slide -->
+
+<!-- ![(Insert figure legend)](graphics/CD4-csaw/LaMere2016_fig8.pdf) -->
+
+
+## Answers to key questions
+
+### How do we define the "promoter region" for each gene?
+
+Define empirically using peak-to-promoter distances; validate by
+correlation with expression.
+
+. . .
+
+### How do these histone marks behave in promoter regions?
+
+Location matters! Specific coverage patterns correlated with elevated
+expression.
+
+. . .
+
+### What can we learn about T-cell activation and differentiation?
+
+Epigenetic & expression state of naïve and memory converges late after
+activation, consistent with naïve differentiation into memory.
+
+## Further conclusions & future directions
+
+* "Effective promoter region" is a useful concept but "radius"
+  oversimplifies: seek a better definition
+
+* Coverage profiles were only examined in naïve day 0 samples: further
+  analysis could incorporate time and cell type
+
+* Coverage profile normalization induces degeneracy: adapt a better
+  normalization from peak callers like SICER
+
+* Unimodal distribution of promoter coverage profiles is unexpected
+
+## Further conclusions & future directions
+
+* Experiment was not designed to directly test the epigenetic
+  convergence hypothesis: future experiments could include cultured
+  but un-activated controls
+
+* High correlation between H3K4me3 and H3K4me2 is curious given they
+  are mutually exclusive: design experiments to determine the degree
+  of actual co-occurrence
+  
+## Implications for transplant biology
+
+::: incremental
+
+* Epigenetic regulation through histone methylation is surely involved
+  in immune memory
+
+* Can we stop memory cells from forming by perturbing histone
+  methylation?
+
+* Can we disrupt memory cell function during rejection by perturbing
+  histone methylation?
+
+* Can we suggest druggable targets for better immune suppression by
+  looking at epigenetically upregulated genes in memory cells?
+
+:::
+
+## Acknowledgements
+
+* My mentors, past and present: Drs. Terry Gaasterland, Daniel
+  Salomon, and Andrew Su
+
+* My committee: Drs. Nicholas Schork, Ali Torkamani, Michael
+  Petrascheck, and Luc Teyton.
+
+* My many collaborators in the Salomon Lab
+
+* The Scripps Genomics Core
+
+* My parents, John & Chris Thompson
+
+## {.plain}
+
+\centering
+
+\huge
+
+Questions?

slides-notes.org

@@ -0,0 +1,80 @@
+* Notes from lab meeting practice run
+
+** DONE Mechanical issues
+- [X] Blurry slide changes
+  - Solution: use Acrobat for presenting
+- [X] Use widescreen aspect ratio -- option to show 2 figures side by
+  side
+- [X] Header is hard to read/easy to ignore because of color scheme.
+  Consider dark text on white bg instead.
+- [X] No figure numbers
+- [X] No chapter numbers, just "3 parts"
+- [X] Way to display speaker notes alongside slides? Maybe import into
+  PPT?
+  - https://pandoc.org/MANUAL.html#speaker-notes
+
+** TODO Presentation issues
+- [X] Bigger axis labels
+- [X] Better cluster ordering, labeling, and transpose violin plots
+  for consistency
+- [X] Whenever possible: micro first to introduce the plot, then macro
+  to show the full plot
+- [ ] For PCoA plots, show just one donor at a time first to show
+  the trend in a simpler context
+
+** TODO Content issues
+- [X] Maybe show more preprocessing, batch correction, etc.
+- [X] Tie conclusions back to intro, add future directions
+- [X] Intro slide for MOFA: how and why
+- [X] Too many bullet points. Don't need to write everything I say.
+  Move to speaker notes.
+- [X] Intro the histone marks and why we picked them
+- [X] Brief 30 second intro to RNA-seq & ChIP-seq
+- [X] Rephrase 3 topics as questions/hypotheses
+- [X] Talk about 3 main take-home points at the beginning as well as
+  the end
+- [X] On summary slides, bullets on left, image on right for each
+  bullet
+- [X] Time was around 40 minutes, so add at least 5 minutes of content
+- [ ] Keep reserve slides at the end with cut figures in case they
+  come in handy for answering audience questions
+
+* DONE Notes from Sabah
+
+- [X] Slide 1: Is the title final? If not, would adjust to (also note
+  space in title slide for bioinformaticsanalysis) "Bioinformatic
+  analysis of genomic and epigenomic data in the context of CD4+T-cell
+  differentiation and diagnosis and treatment of transplant rejection"
+- [X] Slide with organ bar chart: Adjust title to 'Organ donation
+  statistics for the USA in 2018', remove from bottom and make image
+  itself bigger
+- [X] What's the connection between organ transplant, graft rejection,
+  and immune response? Make that clear in the transition between
+  slides. We now want to know about graft rejection because.... why?
+  what about what we just learned with the organ transplants directly
+  connects?
+- [X] Condense these bullet points. The previous set of bullet points
+  is a perfect example of spacing and length readable in a short
+  amount of time for the audience
+- [X] More time on allografting and less time on graft rejection. What
+  is it? How does it work? Provide a brief example/image right before
+  the chart
+- [X] Rejection and immmuno suppressive drugs -- this is a great
+  transition (well explained) but again the bullet points need to be
+  condensed. Bring in an image with these as well to give the audience
+  'a visual break' before you intro your topics
+- [X] I like the update to thesis topics. I would adjust such that 'my
+  thesis topics' is replaced with the overarching question you want to
+  answer for these 3 topics and make that the heading.
+- [X] Then, introduce the 3 topics in the next slide (blue font of
+  topic 1, 2... etc)
+- [X] Then, introduce the additional text for each topic in the next
+  slide
+- [X] You have the 'memory cells' slides repeated 4x, and I see that
+  you're highlighting different sections each time. Pair the heading
+  to match with this (what you want to say in each as the take-home) >
+  having the same heading repeated
+
+
+* Useful links
+- https://pandoc.org/MANUAL.html#speaker-notes

thesis.lyx

@@ -6220,7 +6220,7 @@ status collapsed
 \begin_layout Plain Layout
 \align center
 \begin_inset Graphics
-	filename graphics/CD4-csaw/MOFA-varExplaiend-matrix-CROP.png
+	filename graphics/CD4-csaw/MOFA-varExplained-matrix-CROP.png
 	lyxscale 25
 	width 45col%
 	groupId mofa-subfig

vcs-check.py

@@ -14,11 +14,11 @@ def check_output_lines(*args, **kwargs):
 
 git_tracked_files = set(check_output_lines(
     ["git", "ls-tree", "-r", "HEAD", "--name-only"],
-    text = True))
+    universal_newlines = True))
 
 snakemake_untracked_files = set(run(
     ["snakemake", "--list-untracked"],
-    capture_output = True, text = True, check = True
+    stdout = PIPE, stderr = PIPE, universal_newlines = True, check = True
 ).stderr.rstrip('\n').split('\n'))
 
 all_files = set()
@@ -29,7 +29,7 @@ for curdir, subdirs, files in os.walk('.'):
             continue
         all_files.add(os.path.normpath(os.path.join(curdir, f)))
 
-snakemake_summary_output = check_output(['snakemake', '--summary'], text = True, stderr=DEVNULL)
+snakemake_summary_output = check_output(['snakemake', '--summary'], universal_newlines = True, stderr=DEVNULL)
 snakemake_summary_table = pandas.read_csv(StringIO(snakemake_summary_output), sep='\t')
 snakemake_generated_files = {os.path.normpath(f) for f in snakemake_summary_table.output_file}