Gene-gene correlations using PanCancer expression and copy number data.
Our first step is to authenticate with Google -- you will need to be a member of a Google Cloud Platform (GCP) project, with authorization to run BigQuery jobs in order to run this notebook. If you don't have access to a GCP project, please contact the ISB-CGC team for help (www.isb-cgc.org)
# Running notebook locally...
!gcloud auth login
Your browser has been opened to visit:
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[11806:11825:0508/110154.885591:ERROR:browser_process_sub_thread.cc(217)] Waited 6 ms for network service
Opening in existing browser session.
WARNING: `gcloud auth login` no longer writes application default credentials.
If you need to use ADC, see:
gcloud auth application-default --help
You are now logged in as [dgibbs@systemsbiology.org].
Your current project is [isb-cgc-02-0001]. You can change this setting by running:
$ gcloud config set project PROJECT_ID
## IF YOU'RE IN GOOGLE COLAB ##
from google.colab import auth
try:
auth.authenticate_user()
print('You have been successfully authenticated!')
except:
print('You have not been authenticated.')
Once you're authenticated, we'll begin getting set up to pull data out of BigQuery.
The first step is to initialize the BigQuery client. This requires specifying a Google Cloud Platform (GCP) project id in which you have the necessary privileges (also referred to as "roles") to execute queries and access the data used by this notebook.
Below, we use a GCP project called isb-cgc-bq
. If you have your own GCP project that you would like to use instead, please edit the line below that sets the project_id
variable before running the next cell.
from google.cloud import bigquery
try:
project_id = 'isb-cgc-02-0001'
bqclient = bigquery.Client(project=project_id)
print('BigQuery client successfully initialized')
except:
print('Failure to initialize BigQuery client')
/home/davidgibbs/.local/lib/python3.6/site-packages/google/auth/_default.py:66: UserWarning: Your application has authenticated using end user credentials from Google Cloud SDK. We recommend that most server applications use service accounts instead. If your application continues to use end user credentials from Cloud SDK, you might receive a "quota exceeded" or "API not enabled" error. For more information about service accounts, see https://cloud.google.com/docs/authentication/ warnings.warn(_CLOUD_SDK_CREDENTIALS_WARNING)
BigQuery client successfully initialized
Unless any part of this section fails to run, you only need to look at this in detail if you are interested in understanding how this notebook works or in modifying it for your own purposes.
Note that running this section alone will take about 5 minutes due to the sizes of some of the libraries being imported, as well as the number of dependent libraries.
Of course, once this section has been run, you will be able to run, modify, and re-run any of the later sections of this notebook without having to come back and rerun this section (as long as you have not lost your connection to the Jupyter server).
Import NumPy, Pandas, and seaborn
import numpy as np
import pandas as pd
import seaborn as sns
We define two convenience functions here:
runQuery
: a relatively generic BigQuery query-execution wrapper function which can be used to run a query in "dry-run" mode or not: the call to the query()
function itself is inside a try/except
block and if it fails we return None
; otherwise a "dry" will return an empty dataframe, and a "live" run will return the query results as a dataframe
checkQueryResults
: a generic function that makes sure that what was returned is a dataframe, and checks how many rows are in the returned dataframe
def runQuery ( client, qString, dryRun=False ):
print ( "\n in runQuery ... " )
if ( dryRun ):
print ( " dry-run only " )
## set up QueryJobConfig object
job_config = bigquery.QueryJobConfig()
job_config.dry_run = dryRun
job_config.use_query_cache = True
job_config.use_legacy_sql = False
## run the query
try:
query_job = client.query ( qString, job_config=job_config )
## print ( " query job state: ", query_job.state )
except:
print ( " FATAL ERROR: query execution failed " )
return ( None )
## return results as a dataframe (or an empty dataframe for a dry-run)
if ( not dryRun ):
try:
df = query_job.to_dataframe()
if ( query_job.total_bytes_processed==0 ):
print ( " the results for this query were previously cached " )
else:
print ( " this query processed {} bytes ".format(query_job.total_bytes_processed) )
if ( len(df) < 1 ):
print ( " WARNING: this query returned NO results ")
return ( df )
except:
print ( " FATAL ERROR: query execution failed " )
return ( None )
else:
print ( " if not cached, this query will process {} bytes ".format(query_job.total_bytes_processed) )
## return an empty dataframe
return ( pd.DataFrame() )
def checkQueryResults ( qr ):
print ( "\n in checkQueryResults ... " )
if ( not isinstance(qr, pd.DataFrame) ):
print ( " query execution failed! " )
return ( False )
else:
if ( len(qr) > 0 ):
print ( " # of rows in query results: {} ".format(len(qr)) )
print ( "\n", qr.head() )
else:
print ( " query returned NO results ?!? " )
return ( True )
def build_cohort ( study ):
qString = """
WITH
--
-- we start with the clinical table
--
cohort AS (
SELECT
acronym as Study,
bcr_patient_barcode as ParticipantBarcode
FROM
`isb-cgc-01-0008.Filtered.clinical_PANCAN_patient_with_followup_filtered`
WHERE
acronym = '__study__'
)
""".replace('__study__',study)
return(qString)
def select_genes ( dtype, n ):
if dtype == 'expr':
qString = """
selected_genes AS (
SELECT
Symbol,
STDDEV(normalized_count) AS sigmaExp
FROM
`isb-cgc-01-0008.Filtered.EBpp_AdjustPANCAN_RNASeqV2_filtered`
WHERE
Symbol IS NOT NULL
AND ParticipantBarcode IN (
SELECT
ParticipantBarcode
FROM
cohort)
GROUP BY
1
ORDER BY
sigmaExp DESC
LIMIT
__n__ )
""".replace('__n__', str(n))
elif dtype == 'cnv':
qString = """
selected_genes AS (
SELECT
Gene_Symbols as Symbol,
STDDEV(GISTIC_Calls) AS sigmaExp
FROM
`isb-cgc-01-0008.Filtered.all_CNVR_data_by_gene_filtered`
WHERE
Symbol IS NOT NULL
AND ParticipantBarcode IN (
SELECT
ParticipantBarcode
FROM
cohort)
GROUP BY
1
ORDER BY
sigmaExp DESC
LIMIT
__n__ )
""".replace('__n__', str(n))
else:
#
# Could be some other gene selection function here ##
#
qString = ''
return(qString)
def get_expr_data(i):
qString = """
expr_data__i__ AS (
SELECT
Symbol,
ParticipantBarcode,
SampleBarcode,
normalized_count as expr,
DENSE_RANK() OVER (PARTITION BY SampleBarcode ORDER BY normalized_count ASC) AS rankExpr
FROM
`isb-cgc-01-0008.Filtered.EBpp_AdjustPANCAN_RNASeqV2_filtered`
WHERE
Symbol IS NOT NULL AND
Symbol IN (
SELECT
Symbol
FROM
selected_genes)
AND ParticipantBarcode IN (
SELECT
ParticipantBarcode
FROM
cohort)
)
""".replace('__i__', '_'+str(i))
return(qString)
def join_data(i,j):
qString = """
j_data AS (
SELECT
expr_data_1.Symbol as expr_data_1_Symbol,
expr_data_1.SampleBarcode,
expr_data_1.rankExpr as expr_data_1_rankExpr,
expr_data_1.expr,
expr_data_2.Symbol as expr_data_2_Symbol,
expr_data_2.SampleBarcode,
expr_data_2.rankExpr as expr_data_2_rankExpr,
expr_data_2.expr
FROM
expr_data__i__ JOIN expr_data__j__
ON
expr_data__i__.SampleBarcode = expr_data__j__.SampleBarcode
AND expr_data__i__.Symbol > expr_data__j__.Symbol
)
""".replace('__i__', '_'+str(i)).replace('__j__', '_'+str(j))
return(qString)
def comp_corr(i,j):
qString = """
corr_table AS (
SELECT
expr_data__i___Symbol,
expr_data__j___Symbol,
CORR(expr_data__i___rankExpr,expr_data__j___rankExpr) AS corr
FROM
j_data
GROUP BY
1,2
ORDER BY
corr DESC
)
""".replace('__i__', '_'+str(i)).replace('__j__', '_'+str(j))
return(qString)
def final( last_table ):
qString = """
SELECT * FROM __last_table__
""".replace('__last_table__', last_table)
return(qString)
def build_query( study, dtype, size ):
i = '1'
j = '2'
sql = (
build_cohort( study ) + ',\n' +
select_genes ( dtype, size ) + ',' +
get_expr_data(i) + ',\n' +
get_expr_data(j) + ',\n' + #### change here
join_data(i,j) + ',\n' +
comp_corr(i,j) + '\n' +
final( 'corr_table' )
)
return(sql)
Choose a TCGA study, number of genes, and the data source to use in ranking genes.
# select a tumor type
studyList = [ 'ACC', 'BLCA', 'BRCA', 'CESC', 'CHOL', 'COAD', 'DLBC', 'ESCA',
'GBM', 'HNSC', 'KICH', 'KIRC', 'KIRP', 'LAML', 'LGG', 'LIHC',
'LUAD', 'LUSC', 'MESO', 'OV', 'PAAD', 'PCPG', 'PRAD', 'READ',
'SARC', 'SKCM', 'STAD', 'TGCT', 'THCA', 'THYM', 'UCEC', 'UCS', 'UVM' ]
study = studyList[6]
# choosing which genes to look at
n = 100 # the n most variable genes
# building the query string
sql = build_query (study, 'expr', n)
# print(sql)
# calling Google! #
res0 = runQuery ( bqclient, sql, dryRun=False )
in runQuery ... this query processed 10416423703 bytes
res0.shape
(4950, 3)
res0['index'] = range(0,4950)
res0 [0:10]
expr_data_1_Symbol | expr_data_2_Symbol | corr | index | |
---|---|---|---|---|
0 | PGA4 | LIPF | 0.999086 | 0 |
1 | PGC | PGA4 | 0.998607 | 1 |
2 | PGC | LIPF | 0.998592 | 2 |
3 | PGA3 | LIPF | 0.998415 | 3 |
4 | PGA4 | PGA3 | 0.998272 | 4 |
5 | PGC | PGA3 | 0.997350 | 5 |
6 | C1QB | C1QA | 0.958305 | 6 |
7 | COL3A1 | COL1A1 | 0.942048 | 7 |
8 | COL1A2 | COL1A1 | 0.933614 | 8 |
9 | COL3A1 | COL1A2 | 0.900852 | 9 |
import seaborn as sns
sns.set(style = 'darkgrid')
sns.lmplot(x='index', y='corr', data=res0)
/home/davidgibbs/.local/lib/python3.6/site-packages/scipy/stats/stats.py:1713: FutureWarning: Using a non-tuple sequence for multidimensional indexing is deprecated; use `arr[tuple(seq)]` instead of `arr[seq]`. In the future this will be interpreted as an array index, `arr[np.array(seq)]`, which will result either in an error or a different result. return np.add.reduce(sorted[indexer] * weights, axis=axis) / sumval
<seaborn.axisgrid.FacetGrid at 0x7fdd9444ea58>