README 
--------
This project contains code for using the weighted simplicial complex unmixing m$

There are several key folders to the project.  The doc folder contains README i$

The src folder contains the core source code. The post processing folder contai$
code to post-process inferences that are not simplicial complexes.  The extras $


Standalone 
-------------

Included in the src/wrappers/runWSCUnmix/for_redistribution folder is a standalone deployable compiled from matlab.  The standalone application can be downloaded, and executed in the usual manner.  For Mac / *NIX systems, this is ./MyAppInstaller_web.install  The popup will walk the user through the installation process, including download and installation of the matlab runtime component (mrc) if not yet installed.  Following the installation procedure from the popup, one can execute the pipeline -- parsing, unmixing, merger and output -- in the following manner:
./runWSCUnmix_run.sh <location of mrc> <directory of input files> -theta <thetaVecVal> -gamma <gammaVal> -sigma <sigmaVal> -kupper <k_upperVal> -output <outputDir> {-r,-d,-dr,-rd}

Notes on execution -- all flags and values are required.  thetaVec is a vector of length 7 separated by commas but no spaces.  the final flag is a mode flag.  -dr and -rd refer to data that may be either RNA or DNA data in the directory, -d looks only for DNA formatted data, and -r looks only for RNA data.  DNA data is input as level 4 TCGA data, while RNA data is input as level 3 RNASeq data from TCGA.  For details on the file formats, reference cancer.gov.  These files are expected to be csvs, with .txt extensions.  The code includes logic to look recursively through child folders in the file structure.

The output consists of a set of .txt and .csv files with prefixes specified by <outputDir> and suffixes relating to the output parameters: _V and _gene_list for instance.

Dependencies
-------------
SeDuMi, MVES, 2-stage medoidshift clustering, maximal Cliques, and fuzzy membership clustering.

SeDuMi is an optimization package used by MVES
MVES is minimum volume enclosing simplex code used in previous versions of the work as well as this work.
2-stage medoidshift embeds the ideas presented in Roman et al. 2016 for use here.
getFuzzyMembershipClustering allows for mixed membership in each of the phylogenetic branches of tumor evolution.
maximalCliques finds maximal cliques in an adjacency matrix.

USAGE
--------

[V,A,data,VProj,M,I,E,K,CIp,Ps,Fs,RW,penDf,penPf,dimList] = ...
 weightedSCUnmixMainSliver(data,theta,gamma,c,sigma)
is the main function for the core unmixing problem

Inputs:
-------
data is a samples * features matrix in principal components space of the desired gene / protein features
theta is the parameter used in the sliver-based dimensionality detection module (it is a scalar between 0 and 1).  The larger this value, the higher the perceived noise in the data.
gamma is the parameter used to control the weight of the conditional versus prior portion of the probability model used as the objective function.  Higher values of gamma represent higher noise levels.  Gamma = 0 corresponds to the 'hard unmix' version of the problem presented in Schwartz and Shackney, 2010.  We gamma =1.1 in the corresponding manuscript.
c is the coefficient matrix (loading matrix) relating scores (data) to the original values in gene space (non-PC space).
sigma is the parameter to control for the number of standard deviations past the mean to look for in the cluster-wise dimensionality detection module.  Higher values of sigma correspond to more conservative cluster-wise dimension estimates.  We use sigma =  3 in the corresponding manuscript.

Outputs:
--------
V is a matrix representing inferred vertices correspondent to subpopulation genome profiles (in reduced dimensionality space)
A is the adjacency matrix of the simplicial body where vertices are outlined by V.  It is also a matrix.
data is an echo of the data that was unmixed
VProj is a matrix projecting V into the full-dimensional PC space of data.
M represents the percentage-wise membership of each data point in each cluster/sub-simplex/phylogenetic branch.
I,E,K,CIp,Ps are the eigenvalues, errors, initial vertices, and projections, as outlined in earlier works.  They are presented, but not used in downstream analysis for the corresponding publication.
Fs are the mixture fractions in each sub-simplex for each data point.
RWs are the re-weights -- the recomputed weights for each data point for each vertex.
penPf and penDf are the penalty functions for the prior (Pf) and distance / conditional (Df) portions of the final iteration of the objective function.
dimList is the list of dimensions used for each sub-simplex.

If the returned A does not represent 1 connected component, the post-processing functions must be used.  The main post-processing function is as follows:
[Vnew,Anew]=determine_min_sc(V,A,s)

Input
----- 
V and A are the VProj and A generated from the main core function
s is the representation of data used as input for the main unmixing function

Output
-------
Vnew and Anew are the replacements for VProj and A from the core unmixing.

If the core unmixing is used, the M and F values will need to be recomputed.  The named functions perform those tasks.

This code is copyright 2017 Carnegie Mellon University, and can be freely used and modified.  The code was written by Theodore Roman, under the supervision of advisor Russell Schwartz.  



Data
--------
Data can be accessed at https://cmu.box.com/s/31xwo01wgca65ixi7c1suzdv6gvh5okp


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