#+startup: beamer
#+TITLE: Structural similarity networks predict
#+TITLE: clinical outcome in early-phase schizophrenia
* Preamble                                                    :ignore:
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#+STARTUP: align fold
#+SEQ_TODO: TODO(t) | DONE(d)
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#+LANGUAGE: en
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#+LATEX_CLASS:  mybeamerposter
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# LATEX_HEADER: \usepackage[absolute,overlay]{textpos}
#+LATEX_HEADER: \graphicspath{{../output/figures/}{../lib/}}
#+LATEX_HEADER: \usepackage[export]{adjustbox}
#+LATEX_HEADER: \usepackage{graphicx,caption}
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# LATEX_HEADER: \title{The demise of the spotted swamp frog}
# LATEX_HEADER: \author{Rob J Hyndman}
# LATEX_HEADER: \footer{
# LATEX_HEADER: \textbf{Philipp Homan, MD, PhD}\\
# LATEX_HEADER: phoman1@northwell.edu\\
# LATEX_HEADER: github.com/philipphoman}
#+LATEX_HEADER: \date{}
# ----------------------------------------------------------------------
** Authors and affiliations                                     :ignore:
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#+LATEX_HEADER: \author{
#+LATEX_HEADER: Philipp Homan$^{1}$, 
#+LATEX_HEADER: Miklos Argyelan$^{1}$,
#+LATEX_HEADER: Pamela DeRosse$^{1}$, 
#+LATEX_HEADER: Delbert Robinson$^{1}$,   
#+LATEX_HEADER: John M. Kane$^{1}$, 
#+LATEX_HEADER: Todd Lencz$^{1}$, 
#+LATEX_HEADER: Anil K. Malhotra$^{1}$
#+LATEX_HEADER: \\
#+LATEX_HEADER: \normalsize{$^{1}$Department of Psychiatry,} 
#+LATEX_HEADER: \normalsize{The Donald and Barbara Zucker}
#+LATEX_HEADER: \normalsize{School of Medicine at Northwell/Hofstra,}
#+LATEX_HEADER: \normalsize{Hempstead, NY}\\
#+LATEX_HEADER: }
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# Set elisp variables need for nice formatting We want no new lines in
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#+BEGIN_SRC emacs-lisp :exports none :results silent

  ; set timestamp format
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  ;(setq org-latex-pdf-process '("latexmk -pdflatex='xelatex
  ;-output-directory=../output/tex/ -interaction nonstopmode' -pdf
  ;-bibtex -f %f"))
  (setq org-latex-logfiles-extensions 
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** End preamble                                                 :ignore:
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* References                                                    :ignore:
\bibliographystyle{nature}
\nobibliography{master} 
* The poster
:PROPERTIES:
:BEGIN:
:BEAMER_env: fullframe
:END:

** Code                                                       :ignore:
# First, make sure all variables are availabe
#+HEADER: :exports none
#+BEGIN_SRC R :results silent :session
source("../src/fe_func.R")
source("../src/fe_load.R")

fef <- read.csv("../data/fe_cidar.csv")
feo <- read.csv("../data/fe_omega3.csv")
hca <- read.csv("../data/fe_hcm.csv")

# Load necessary results tables
roistab  <- read.csv("../output/tables/fe_freesurfer_roinames.csv")
roitvalstab  <- read.csv("../output/tables/fe_freesurfer_roitvals.csv")
permuttab <- read.csv("../output/tables/fe_msn_permut_rsq.csv")
bootstraptab <- read.csv("../output/tables/fe_msn_bootstrap_rsq.csv")
crossvaltab <- read.csv("../output/tables/fe_msn_crossvalidation.csv")
graphsumtab <- read.csv("../output/tables/fe_freesurfer_graphsum.csv")	
plsrtab <- read.csv("../output/tables/fe_msn_plsscore_rs.csv")	
deltadegreestab <- read.csv("../output/tables/fe_freesurfer_deltadegrees.csv")


# Custom functions
pvalstr <- function(pval) {
	if (pval < 0.001) {
		return("< 0.001")
	} else {
		return(paste("=", round(pval, 3)))
	}
}

#+END_SRC

#+HEADER: :exports none
#+BEGIN_SRC R :results silent :session :cache yes
# Merge data sets and keep only interesting variables
# Rename variables for later
fefa <- fef %>% dplyr::filter(day==0&included16w==1) %>%
								dplyr::mutate(study="CIDAR", group="SZ") %>%
                dplyr::select(dup, iq, mccb, bprs, bprs_td, bprs_tdbl, 
                              age, sex, race, hasmri, study, group, 
															education,
															bmi, class, alcohol, drugs)
															
feoa <- feo %>% dplyr::filter(day==0&included16w==1) %>%
								dplyr::mutate(study="Omega3", group="SZ") %>%
                dplyr::select(dup, iq, mccb, bprs, bprs_td, bprs_tdbl, 
                              age, sex, race, hasmri, study, group, 
															education,
															bmi, class, alcohol, drugs)


#hca$male[hca$sex==1] <- 1
#hca$female[hca$sex==2] <- 1
hcab <- hca %>% dplyr::rename(age=age) %>%
        filter(age<50) %>%
        dplyr::select(sex, age, education, iq) %>%
				dplyr::mutate(study="HC",
				       group="HC")
hcmeanage <- round(mean(hcab$age), 1)
hcsdage <- round(sd(hcab$age), 1)
hcmales <- sum(hcab$sex==1, na.rm=TRUE)
hcfemales <- sum(hcab$sex==2, na.rm=TRUE)
feffeo <- rbind(fefa, feoa) %>% filter(hasmri==1)

# Custom function
parse_agesex <- function() {
  print(paste("(", n_females, " females; mean age [SD] = ", 
              meanage, " [", sdage, "])", sep=""))
}

parse_n <- function(group) {
  switch(group,
    sz={
      print(paste("(/N/ = ", n_partic, ")", sep=""))
			},
    hc={
      print(paste("(/N/ = ", n_partic_hc, ")", sep=""))
			})
}

# R version
rvers <- version$version.string

# Python version
# pyvers <- system("python --version")
# pysurfvers <- system("pip freeze | grep pysurf")
#pyvers <- "2.7.13"
#pysurfvers <- "0.7"
pyplusvers <- system("pyv=$(python -V 2>&1); echo $pyv", intern=TRUE)
pysurfplusvers <- system("pip list | grep pysurf", intern=TRUE)
			 
# Custom variables
n_nodes <- 2 * nlevels(roistab$name) 
n_partic <- nrow(feffeo)
n_partic_hc <- nrow(hcab)
n_partic_full_bothsamples <- nrow(rbind(fef %>% filter(day==0),
                                        feo %>% filter(day==0)))
n_females <- sum(feffeo$sex==1)
n_males <- sum(feffeo$sex==2)
meanage <- round(mean(feffeo$age, na.rm=TRUE), 1)
sdage <- round(sd(feffeo$age, na.rm=TRUE), 1)

# Cross validation values
cvkfold_k <- crossvaltab$k
cvrsq_mean <- crossvaltab$mean
cvrsq_sd <- crossvaltab$sd

# Permutation and bootstrap values
rsqorig <- unique(permuttab$rsq_orig)
npermut <- unique(permuttab$niter)
prsq_pval <- unique(permuttab$prsq_pva)

# PLS correlation values
pls1r <- plsrtab$r[plsrtab$component=="PLS1"]
pls1rpval <- plsrtab$pval[plsrtab$component=="PLS1"]
pls2r <- plsrtab$r[plsrtab$component=="PLS2"]
pls2rpval <- plsrtab$pval[plsrtab$component=="PLS2"]

# Graph summary, drop Cp and keep transitivity
# as the two are essential equal
graphsumtab <- graphsumtab %>% filter(metric!="Cp") %>%
   mutate(metric=recode(metric, 
          transitivity="Cluster coef.",
	        diameter="Diameter",
					E.global="Global efficiency",
					E.local="Local efficiency",
					num.hubs="Number of hubs",
					richclub="Rich club coef.",
					vulnerability="Vulnerability"))

#+END_SRC

** Left column                                                  :BMCOL:
:PROPERTIES:
:BEAMER_col: 0.45\textwidth
:BEAMER_opt: [t]
:END:
*** Background                                                 :B_block:
:PROPERTIES:
:BEAMER_env: block
:END:
- Schizophrenia has long been considered a disorder of dysconnectivity
  in the brain
- Using graph theory, we computed statistical similarity networks for
  each individual (Fig [[figflowchart]], [[figshrinkage]]) in two
  early-phase schizophrenia cohorts src_R[:session]{parse_n("sz")}
  {{{results((/N/ = 82))}}} and in healthy controls
  src_R[:session]{parse_n("hc")} {{{results((/N/ = 77))}}} and tested
  whether network architecture predicted treatment response

*** Methods: Structural similarity networks                    :B_block:
:PROPERTIES:
:BEAMER_env: block
:END:

\captionsetup{justification=justified,width=.85\linewidth}
#+NAME: figflowchart
#+CAPTION: *Analysis flow chart.*
#+CAPTION: The similarity between any pair of region was
#+CAPTION: estimated by calculating the
#+CAPTION: Kullback-Leibler (KL) divergence of their
#+CAPTION: probability distributions, resulting in 
#+CAPTION: a similarity matrix. 
#+CAPTION: The similarity matrix 
#+CAPTION: was then thresholded into a binary matrix to 
#+CAPTION: create a network graph. Graph-based 
#+CAPTION: degree (or hubness) for each node was then
#+CAPTION: calculated for each individual participant. 
#+CAPTION: Nodal degrees were then entered as
#+CAPTION: predictors into a partial
#+CAPTION: least squares regression, using individual
#+CAPTION: treatment response slopes as outcome
#+CAPTION: measure.
#+ATTR_LATEX: :width 0.85\textwidth 
[[file:fe_freesurfer_flowchart.pdf]]

*** Methods: Individual treatment response                     :B_block:
:PROPERTIES:
:BEAMER_env: block
:END:

\captionsetup{justification=justified,width=.85\linewidth}
#+NAME: figshrinkage
#+CAPTION: *Partial pooling to regularize individual response slopes.* 
#+CAPTION: *A.* *Individual time courses for all participants*
#+CAPTION: *from the first schizophrenia cohort.* 
#+CAPTION: Partial pooling regularized
#+CAPTION: the individual slopes, i.e., the influence
#+CAPTION: of outliers with only few assessments was attenuated. 
#+CAPTION: *B.* *The partial pooling effect*
#+CAPTION: *is demonstrated by the individual responses being*
#+CAPTION: *pulled toward the average treatment effect.*
#+CAPTION: As a consequence, outliers are less influential.
#+CAPTION: *C, D.* The same is shown for the second schizophrenia
#+CAPTION: cohort.
#+CAPTION: Dotted ellipses indicate confidence regions for the
#+CAPTION: average treatment effect.
#+ATTR_LATEX: :width 0.85\textwidth
[[file:fe_freesurfer_shrinkage.pdf]]

** Right column                                                 :BMCOL:
:PROPERTIES:
:BEAMER_col: 0.45\textwidth
:BEAMER_opt: [t]
:END:
*** Results: Partial least squares regression                  :B_block:
:PROPERTIES:
:BEAMER_env: block
:END:

- Individual differences in the configuration of structural similarity
  networks explained a significant proportion of variance in treatment
  response (Fig. [[figplsbrains]])
- Exploratory analysis: increased clustering and decreased network
  integration in patients compared to controls (Fig. [[figge]],
  [[figclus]])

\captionsetup{justification=justified,width=.8\linewidth}
#+NAME: figplsbrains
#+CAPTION: *PLS scores with individual treatment* 
#+CAPTION: *response and contribution of cortical nodes*
#+CAPTION: *in the schizophrenia cohort*
#+CAPTION: Nodal degree for each of 
#+CAPTION: the src_R[:session]{n_nodes} {{{results(68)}}}
#+CAPTION: was entered into a partial least squares (PLS) 
#+CAPTION: regression, with individual treatment response 
#+CAPTION: slopes as outcome measure. The first two
#+CAPTION: PLS components explained a significant proportion
#+CAPTION: of variance in treatment response. *A, B.* The first
#+CAPTION: PLS component correlated most strongly with
#+CAPTION: nodal degree of orbito- and prefrontal cortices
#+CAPTION: and posterior cingulate cortex. Note that
#+CAPTION: more negative slopes meant better
#+CAPTION: treatment response. 
#+CAPTION: *B, C.* The second PLS component correlated most
#+CAPTION: most strongly with superior temporal, precentral,
#+CAPTION: and middle cingulate brain areas.
#+ATTR_LATEX: :width 0.8\textwidth
[[file:fe_freesurfer_plsbrains.pdf]]

*** Results: Increased clustering in patients                  :B_block:
:PROPERTIES:
:BEAMER_env: block
:END:

**** Left
:PROPERTIES:
:BEAMER_col: 0.48
:BEAMER_opt: [T]
:END:

\captionsetup{justification=justified,width=.8\linewidth}
#+NAME: figge
#+CAPTION: *Decreased network integration in*
#+CAPTION: *schizophrenia patients compared to controls.*
#+CAPTION: Means with error bands
#+CAPTION: are shown.
#+CAPTION: Non-overlapping error bands 
#+CAPTION: indicate significant group differences (/P/ < 0.05).
#+ATTR_LATEX: :width 0.9\textwidth :options page=3
[[file:fe_freesurfer_graphsum_individual.pdf]]

**** Right
:PROPERTIES:
:BEAMER_col: 0.48
:BEAMER_opt: [T]
:END:

\captionsetup{justification=justified,width=.8\linewidth}
#+NAME: figclus
#+CAPTION: *Increased clustering in schizophrenia patients*
#+CAPTION: *compared to controls.*
#+CAPTION: Means with error bands are shown.
#+CAPTION: Non-overlapping error bands 
#+CAPTION: indicate significant group differences (/P/ < 0.05).
#+ATTR_LATEX: :width 0.9\textwidth :options page=9
[[file:fe_freesurfer_graphsum_individual.pdf]]

*** Conclusions                                                :B_block:
:PROPERTIES:
:BEAMER_env: block
:END:
- These data suggest a potential link between brain network morphology
  and clinical outcome in early-phase schizophrenia