Initialize the environment


In [1]:
import theano
import numpy as np
import matplotlib.pyplot as plt
%matplotlib inline

In [2]:
src_dir='../src' # source directory
run_dir_prefix='../MDBN_run/OV_Batch_' # directory with the results of previous runs
data_dir='../data' # directory with the data files

In [3]:
import sys
sys.path.insert(0, src_dir)
import MDBN
import main

Load the experiment results


In [4]:
run=0
uuid='73dab4ea3383b2666d1220969a7feba8' 
timestamp='20170220T114308' # specify the date and time of the run in the format YYYYmmddTHHMMSS
run_dir=run_dir_prefix+timestamp
runfile='Exp_%s_run_%s.npz' % (uuid, run) # location of the experiment results
mdbn = MDBN.MDBN()
config, dbn_dict = mdbn.load_network(runfile, run_dir)

Configuration of the experiment


In [5]:
config


Out[5]:
{u'dbns': {u'DM': {u'batchSize': 1,
   u'datafile': u'TCGA_Data/3.Methylation_0.5.out',
   u'epochs': [20, 800],
   'inputNodes': 15418,
   u'k': 1,
   u'lambdas': [0.0, 1.0],
   u'layersNodes': [400, 40],
   u'lr': [0.0005, 0.1],
   u'persistent': False},
  u'GE': {u'batchSize': 1,
   u'datafile': u'TCGA_Data/3.GE1_0.5.out',
   u'epochs': [20, 800],
   'inputNodes': 16046,
   u'k': 1,
   u'lambdas': [0.0, 1.0],
   u'layersNodes': [400, 40],
   u'lr': [0.0005, 0.1],
   u'persistent': False},
  u'ME': {u'batchSize': 1,
   u'datafile': u'TCGA_Data/3.miRNA_0.5.out',
   u'epochs': [20],
   'inputNodes': 799,
   u'k': 10,
   u'lambdas': [0.0, 0.1],
   u'layersNodes': [40],
   u'lr': [0.0005],
   u'persistent': False}},
 u'name': u'ov_config_20_1_05.json',
 u'p': 0.5,
 u'pathways': [u'ME', u'GE', u'DM'],
 u'runs': 5,
 u'seed': 1234,
 u'top': {u'batchSize': 1,
  u'epochs': [800, 800],
  'inputNodes': 120,
  u'k': 1,
  u'layersNodes': [24, 3],
  u'lr': [0.1, 0.1],
  u'persistent': False},
 u'uuid': u'73dab4ea3383b2666d1220969a7feba8'}

Load the dataset and visualize the input of the pathways


In [6]:
datafiles = main.prepare_TCGA_datafiles("OV",config,data_dir)

Look at the joint layer representation


In [7]:
dbn_output_list=[]
for key in config['pathways']:
    dbn_output, _ = dbn_dict[key].MLP_output_from_datafile(datafiles[key], datadir=data_dir)
    dbn_output_list.append(dbn_output)

In [8]:
joint_layer = np.concatenate(dbn_output_list,axis=1)
plt.imshow(joint_layer, interpolation='none', cmap='gray')
plt.axis('tight')
plt.colorbar()


Out[8]:
<matplotlib.colorbar.Colorbar at 0x122b7c490>

Check the weights distributions


In [10]:
plt.hist(dbn_dict['GE'].rbm_layers[0].W.get_value())


Out[10]:
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  array([  0.00000000e+00,   6.00000000e+00,   4.36000000e+02,
           2.36500000e+03,   6.15000000e+03,   5.33600000e+03,
           1.50600000e+03,   2.25000000e+02,   2.20000000e+01,
           0.00000000e+00]),
  array([  0.00000000e+00,   4.00000000e+00,   4.05000000e+02,
           2.31100000e+03,   5.65200000e+03,   5.22000000e+03,
           2.15000000e+03,   3.00000000e+02,   4.00000000e+00,
           0.00000000e+00]),
  array([  0.00000000e+00,   3.00000000e+00,   2.24000000e+02,
           2.36200000e+03,   5.70600000e+03,   5.32300000e+03,
           2.18900000e+03,   2.38000000e+02,   1.00000000e+00,
           0.00000000e+00]),
  array([  1.00000000e+00,   6.90000000e+01,   7.95000000e+02,
           2.89100000e+03,   5.49400000e+03,   4.87800000e+03,
           1.70400000e+03,   2.09000000e+02,   5.00000000e+00,
           0.00000000e+00]),
  array([    0.,    18.,   464.,  2587.,  6148.,  4839.,  1576.,   346.,
            68.,     0.])],
 array([-0.04820448, -0.03831397, -0.02842346, -0.01853295, -0.00864244,
         0.00124807,  0.01113858,  0.02102909,  0.0309196 ,  0.04081011,
         0.05070062]),
 <a list of 400 Lists of Patches objects>)

Check final results


In [11]:
top_output = dbn_dict['top'].get_output(theano.shared(joint_layer,borrow=True))
plt.imshow((top_output>0.8)*np.ones_like(top_output)-(top_output<0.2)*np.ones_like(top_output),interpolation='none',extent=[0,3,385,0])
plt.colorbar()
plt.axis('tight')
plt.xticks(np.arange(0.5,3.5,1),('0','1','2'))


Out[11]:
([<matplotlib.axis.XTick at 0x126431d10>,
  <matplotlib.axis.XTick at 0x126408e90>,
  <matplotlib.axis.XTick at 0x136911350>],
 <a list of 3 Text xticklabel objects>)

In [12]:
plt.imshow(top_output, interpolation='none',extent=[0,3,385,0], cmap='gray')
plt.axis('tight')
plt.colorbar()
plt.xticks(np.arange(0.5,3.5,1),('0','1','2'))


Out[12]:
([<matplotlib.axis.XTick at 0x11241ab90>,
  <matplotlib.axis.XTick at 0x1372de410>,
  <matplotlib.axis.XTick at 0x137b99fd0>],
 <a list of 3 Text xticklabel objects>)

In [13]:
plt.hist(top_output)


Out[13]:
([array([ 234.,    0.,    0.,    0.,    0.,    0.,    0.,    0.,    0.,  151.]),
  array([ 234.,    0.,    0.,    0.,    0.,    0.,    0.,    0.,    0.,  151.]),
  array([ 318.,    0.,    1.,    0.,    2.,    0.,    1.,    2.,    2.,   59.])],
 array([  4.72879414e-20,   9.99998748e-02,   1.99999750e-01,
          2.99999624e-01,   3.99999499e-01,   4.99999374e-01,
          5.99999249e-01,   6.99999124e-01,   7.99998999e-01,
          8.99998873e-01,   9.99998748e-01]),
 <a list of 3 Lists of Patches objects>)

In [14]:
code = (top_output[:,0:3] > 0.5) * np.ones_like(top_output[:,0:3])

In [15]:
from utils import find_unique_classes
U = find_unique_classes(code)
cl = U[0]

In [16]:
max_cl = np.max(cl)
plt.hist(cl,bins=np.arange(-0.5,max_cl + 1.5,1))


Out[16]:
(array([ 170.,   64.,  151.]),
 array([-0.5,  0.5,  1.5,  2.5]),
 <a list of 3 Patch objects>)

Check Survival curves for the different classes


In [17]:
import csv
id=[]
with open('../data/'+datafiles['ME']) as f:
    my_csv = csv.reader(f,delimiter='\t')
    id = my_csv.next()

In [18]:
stat={}
with open('../data/TCGA_Data/data_bcr_clinical_data_patient.csv') as f:
    reader = csv.reader(f, delimiter='\t')
    for row in reader:
        patient_id=row[1]
        stat[patient_id]=(row[15],row[16],row[17])

In [19]:
import re
time_list = []
event_list = []
group_list = []
DEAD=1
ALIVE=0
print('The following case IDs were  not found in clinical data')
for index, key in enumerate(id[1:]):
    m = re.match('TCGA-\w+-\d+', key)
    patient_id = m.group(0)
    if patient_id in stat:
        patient_stat = stat[patient_id]
        add_group = True
        try:
            time_list.append(float(patient_stat[2]))
            event_list.append(DEAD)
        except ValueError:
            try:
                time_list.append(float(patient_stat[1]))
                event_list.append(ALIVE)
            except ValueError:
                print('No data for %s' % patient_id)
                add_group = False
        if add_group:
            group_list.append(cl[index])
    else:
        print(patient_id)


The following case IDs were  not found in clinical data
TCGA-24-0981
No data for TCGA-04-1519
No data for TCGA-04-1360
TCGA-01-0639
TCGA-01-0642
No data for TCGA-04-1357
TCGA-01-0628
TCGA-04-1331
TCGA-01-0636
TCGA-01-0633
TCGA-01-0637
TCGA-01-0631
TCGA-01-0630

In [20]:
from lifelines import KaplanMeierFitter
kmf = KaplanMeierFitter()
kmf.fit(time_list,event_observed=event_list)
kmf.plot()


Out[20]:
<matplotlib.axes._subplots.AxesSubplot at 0x13d161590>

In [21]:
T=np.array(time_list)
E=np.array(event_list)
ix = (np.array(group_list) == 0)
kmf.fit(T[ix], E[ix], label='group 0')
ax=kmf.plot()
for i in range(1,3):
    ix=(np.array(group_list)==i)
    kmf.fit(T[ix], E[ix], label='group %d' % i)
    kmf.plot(ax=ax)