Exploration of Tissue Specificity of GABA Receptors using the GTEX Dataset


In [1]:
import NotebookImport
from metaPCNA import *


importing IPython notebook from metaPCNA
importing IPython notebook from Imports
importing IPython notebook from Global_Parameters

In [2]:
import GTEX as GTEX


importing IPython notebook from GTEX
Using downloaded files...

In [3]:
f_win.order().tail()


Out[3]:
LOC283914    0.41
CST2         0.42
C16orf13     0.43
GABRD        0.47
SEMA5B       0.48
Name: fraction overexpressed\n(detrended), dtype: float64

In [4]:
gabr = [g for g in rna_df.index if g.startswith('GABR')]
f = dx_rna.ix[gabr].dropna()
f.join(f_win).sort(f_win.name)


Out[4]:
num_ox num_dx frac p fraction overexpressed (detrended)
GABRA2 141 654 0.22 1.59e-50 -0.31
GABRA4 145 645 0.22 1.39e-46 -0.27
GABRB1 201 629 0.32 8.11e-20 -0.16
GABRP 248 684 0.36 6.25e-13 -0.15
GABRB3 218 684 0.32 1.29e-21 -0.12
GABRG1 189 635 0.30 6.76e-25 -0.12
GABRG3 273 632 0.43 7.10e-04 -0.12
GABRA3 333 602 0.55 1.02e-02 -0.10
GABRA5 281 617 0.46 2.96e-02 -0.09
GABRB2 245 678 0.36 4.92e-13 -0.06
GABRR3 161 339 0.47 3.85e-01 -0.05
GABRR2 319 678 0.47 1.34e-01 -0.04
GABRG2 271 504 0.54 9.92e-02 -0.02
GABRR1 358 631 0.57 8.12e-04 0.03
GABRE 343 684 0.50 9.70e-01 0.04
GABRA1 272 546 0.50 9.66e-01 0.05
GABRQ 435 637 0.68 1.43e-20 0.10
GABRD 607 684 0.89 4.59e-103 0.47

In [5]:
GTEX.plot_tissues_across_gene('GABRD', log=True)



In [6]:
gtex = np.log2(GTEX.gtex)
meta = GTEX.meta
tissue_type = GTEX.tissue_type

GABRD is highly expressed in many areas of the brain as well as in the testis. Interestingly it is the highest expressed subunit in the testis.


In [7]:
mm =  gtex.ix[gabr].dropna().T.groupby(meta['SMTSD']).median()
mm = mm.clip_lower(-10)
mm.rank(1, ascending=False)['GABRD'].order().head(10)


Out[7]:
SMTSD
Brain - Anterior cingulate cortex (BA24)     1
Brain - Frontal Cortex (BA9)                 1
Brain - Cortex                               1
Brain - Cerebellum                           1
Brain - Cerebellar Hemisphere                1
Brain - Caudate (basal ganglia)              1
Brain - Amygdala                             1
Brain - Putamen (basal ganglia)              1
Testis                                       1
Brain - Nucleus accumbens (basal ganglia)    2
Name: GABRD, dtype: float64

Here I'm plotting the different GABA receptors expression distribution in Testes.


In [10]:
fig, ax = subplots(figsize=(10,4))
o = ['GABRA1','GABRA2', 'GABRA3', 'GABRA4', 'GABRA5',
     'GABRB1', 'GABRB2', 'GABRB3',
     'GABRR1', 'GABRR2', 'GABRR3',
     'GABRD','GABRE','GABRP','GABRQ']
c = sns.color_palette('muted', n_colors=7, desat=.7)

dd = gtex.ix[o, ti(tissue_type == 'Testis')].dropna(1)
sns.violinplot(dd.clip_lower(-4.).T, order=o,
               names=[s[4:] for s in o],
               inner='points', alpha=.7,
               color=[c[0]]*5 + [c[1]]*3 + [c[2]]*3 + c[3:])
ax.set_xlabel('GABA subunit')
ax.set_ylabel('GTEX- Testis Expression (Log2)')
prettify_ax(ax)
fig.savefig(FIGDIR + 'Fig_S6.pdf')


There is a correlation of subunit expression in the testis with fraction upregulated in cancer across the GABA subunits.


In [11]:
series_scatter(dx_rna.frac.ix[gabr],
               gtex.ix[gabr].dropna().T.groupby(meta['SMTSD']).median().ix['Testis'])


Looking at co-expression

In the testis


In [12]:
sns.clustermap(gtex.ix[gabr, ti(meta['SMTSD'] == 'Testis')].T.corr())


Out[12]:
<seaborn.matrix.ClusterGrid at 0x7fdecc073ed0>

In the cerebellum


In [13]:
bella = ti(meta['SMTSD'].dropna().str.contains('Cerebellum'))
sns.clustermap(gtex.ix[gabr, bella].T.corr())


Out[13]:
<seaborn.matrix.ClusterGrid at 0x7fdecc05cf10>

For TCGA differential expression


In [14]:
sns.clustermap(dx.ix[gabr].T.corr().clip(-.5,.5))


Out[14]:
<seaborn.matrix.ClusterGrid at 0x7fdebc2ca9d0>