%% BICLUSTERDEMO some examples of how to use the clustergram function
% This example demonstrates some of the options of the *clustergram*
% function. The example uses data from Scherf U, Ross DT, Waltham M, Smith
% LH, Lee JK, Tanabe L, Kohn KW, Reinhold WC, Myers TG, Andrews DT,
% Scudiero DA, Eisen MB, Sausville EA,Pommier Y, Botstein D, Brown PO,
% Weinstein JN. Related Articles, Links "A gene expression database for the
% molecular pharmacology of cancer." Nature Genetics 2000 Mar;24(3):236-44.
% PMID: 10700175

%   Copyright 2003-2004 The MathWorks, Inc.
%   $Revision: 1.1.6.5 $  $Date: 2004/12/24 20:38:12 $

if playbiodemo, return; end % Open in the editor or run step-by-step

%% Load the data into MATLAB
% The data used in this example is a 118x60 table of growth inhibition
% factors when 118 drugs with putatively understood methods of action were
% applied to the NCI60 cell lines.
 
%%
% The original data can be downloaded from
% http://discover.nci.nih.gov/nature2000/data/selected_data/a_matrix118.txt
% For the purpose of this demonstration, the file has been converted to an
% Excel spreadsheet. The *xlsread* function can be used to read in the data
% from the XLS file. 

[numericData, textData] = xlsread('cancerdata.xls');

%% Extract the data from the Excel tables 
% *xlsread* reads the data in the spreadsheet into two variables,
% numericData, which stores numeric values and textData, which stores any
% text values in the table. In this case the first three columns of the
% table are information about the drugs used in the study.

giValues = numericData(:,2:end);
drugMechanism = textData(2:end,1);
drugName = textData(2:end,2);
drug = strcat(drugMechanism,'-',drugName);
drugID = numericData(:,1);
cellLine = textData(1,4:end);
tumorTypes = strtok(cellLine,':');

% Clear data that is no longer needed.

clear numericData textData

%% Impute values for missing data 
% giValues contains some missing data. These are marked as NaN.
% We can choose to remove these values or somehow impute the missing data.
% The function *nanmedian* can be used to find the median of the values in
% the rows or in the columns ignoring any missing values. There are several
% other functions in the Statistics Toolbox that work with NaN data
% including *nanmean*, *nanvar* and *nansum*.

% Find the missing values using the function *isnan*.
missingVals = isnan(giValues);

% Find the row and column medians ignoring NaN values.
colMedians = nanmedian(giValues);
rowMedians = nanmedian(giValues,2);

% Replace the missing values with the row medians.
rowMed = repmat(rowMedians,1,size(giValues,2));
giValues(missingVals) = rowMed(missingVals);

%% Now do the clustering
% The function *clustergram* is used to perform hierarchical clustering and
% to generate a heat map and dendrogram of the data. The simplest form of
% *clustergram* clusters the rows of a data set using correlation as the
% distance metric and average linkage. In this example the drug profiles
% are clustered and the heat map and dendrogram show that drugs with
% similar methods of action clustered together.

clustergram(giValues,'rowlabels',drug,'columnlabels',tumorTypes);

%% Changing the color scheme
% The default color scheme is the red-green color scale that is widely used
% in microarray data analysis. In this example, a different color scheme is
% more useful. The 'colormap' option allows you to specify an alternative
% colormap. The default color scale assumes that the data is centred about
% zero. In this example, the data is not symmetric about zero so by setting
% the 'SymmetricRange' option to false, you will see more dynamic range in
% the heat map.

clustergram(giValues,'rowlabels',drug,'columnlabels',tumorTypes,...
                            'colormap',jet,'symmetricrange',false);
                        
%% Clustering the columns of the data set
% The simplest way to cluster the columns of the data is to transpose the
% data using the ' operator. Note that the column labels and row labels are
% switched and the dendrogram is still horizontal. In this example the cell
% lines are clustered.

clustergram(giValues','columnlabels',drug,'rowlabels',tumorTypes,...
                            'colormap',jet,'symmetricrange',false);
%% Bi-clustering
% To perform two dimensional, or bi-clustering, set the 'dimension' option
% to 2. This clusters both the rows and columns of the data and produces a
% heat map with two dendrograms, in this example one showing the clustering
% of the cell lines and one showing the clustering of the drugs.

clustergram(giValues,'dimension',2,'rowlabels',drug,'columnlabels',tumorTypes,...
                            'colormap',jet,'symmetricrange',false);

%% Changing clustering options
% You can change the settings of the clustering algorithm to use and a
% different distance metric or different linkage method. In this example,
% weighted linkage (WPGMA) is used and the dendrograms highlight different
% clusters with distance less than 10 units apart.

clustergram(giValues,'dimension',2,'rowlabels',drug,'columnlabels',tumorTypes,...
                            'colormap',jet,'symmetricrange',false,...
                            'linkage','weighted','dendrogram',{'color',10});

%%
% If you want even more control over the clustering, you can use the
% clustering functions in the Statistics Toolbox directly. See *yeastdemo*
% for some examples of how to do this.