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-rw-r--r--wqflask/wqflask/my_pylmm/pyLMM/gwas.py213
-rw-r--r--wqflask/wqflask/my_pylmm/pyLMM/kinship.py4
-rw-r--r--wqflask/wqflask/my_pylmm/pyLMM/lmm.py62
-rw-r--r--wqflask/wqflask/my_pylmm/pyLMM/runlmm.py8
4 files changed, 271 insertions, 16 deletions
diff --git a/wqflask/wqflask/my_pylmm/pyLMM/gwas.py b/wqflask/wqflask/my_pylmm/pyLMM/gwas.py
new file mode 100644
index 00000000..52455014
--- /dev/null
+++ b/wqflask/wqflask/my_pylmm/pyLMM/gwas.py
@@ -0,0 +1,213 @@
+# pylmm-based GWAS calculation
+#
+# Copyright (C) 2013 Nicholas A. Furlotte (nick.furlotte@gmail.com)
+# Copyright (C) 2015 Pjotr Prins (pjotr.prins@thebird.nl)
+#
+# This program is free software: you can redistribute it and/or modify
+# it under the terms of the GNU Affero General Public License as
+# published by the Free Software Foundation, either version 3 of the
+# License, or (at your option) any later version.
+
+# This program is distributed in the hope that it will be useful,
+# but WITHOUT ANY WARRANTY; without even the implied warranty of
+# MERCHANTABILITY or FITNESS FOR A PARTICULAR PURPOSE. See the
+# GNU Affero General Public License for more details.
+
+# You should have received a copy of the GNU Affero General Public License
+# along with this program. If not, see <http://www.gnu.org/licenses/>.
+#!/usr/bin/python
+
+import pdb
+import time
+import sys
+# from utility import temp_data
+import lmm
+
+
+import os
+import numpy as np
+import input
+from optmatrix import matrix_initialize
+# from lmm import LMM
+
+import multiprocessing as mp # Multiprocessing is part of the Python stdlib
+import Queue
+
+def compute_snp(j,snp_ids,q = None):
+ # print(j,len(snp_ids),"\n")
+ result = []
+ for snp_id in snp_ids:
+ # j,snp_id = collect
+ snp,id = snp_id
+ # id = collect[1]
+ # result = []
+ # Check SNPs for missing values
+ x = snp[keep].reshape((n,1)) # all the SNPs
+ v = np.isnan(x).reshape((-1,))
+ if v.sum():
+ # NOTE: this code appears to be unreachable!
+ if verbose:
+ sys.stderr.write("Found missing values in "+str(x))
+ keeps = True - v
+ xs = x[keeps,:]
+ if keeps.sum() <= 1 or xs.var() <= 1e-6:
+ # PS.append(np.nan)
+ # TS.append(np.nan)
+ # result.append(formatResult(id,np.nan,np.nan,np.nan,np.nan))
+ # continue
+ result.append(formatResult(id,np.nan,np.nan,np.nan,np.nan))
+ continue
+
+ # Its ok to center the genotype - I used normalizeGenotype to
+ # force the removal of missing genotypes as opposed to replacing them with MAF.
+ if not normalizeGenotype:
+ xs = (xs - xs.mean()) / np.sqrt(xs.var())
+ Ys = Y[keeps]
+ X0s = X0[keeps,:]
+ Ks = K[keeps,:][:,keeps]
+ if kfile2:
+ K2s = K2[keeps,:][:,keeps]
+ Ls = LMM_withK2(Ys,Ks,X0=X0s,verbose=verbose,K2=K2s)
+ else:
+ Ls = LMM(Ys,Ks,X0=X0s,verbose=verbose)
+ if refit:
+ Ls.fit(X=xs,REML=REML)
+ else:
+ #try:
+ Ls.fit(REML=REML)
+ #except: pdb.set_trace()
+ ts,ps,beta,betaVar = Ls.association(xs,REML=REML,returnBeta=True)
+ else:
+ if x.var() == 0:
+ # Note: this code appears to be unreachable!
+
+ # PS.append(np.nan)
+ # TS.append(np.nan)
+ # result.append(formatResult(id,np.nan,np.nan,np.nan,np.nan)) # writes nan values
+ result.append(formatResult(id,np.nan,np.nan,np.nan,np.nan))
+ continue
+
+ if refit:
+ L.fit(X=x,REML=REML)
+ # This is where it happens
+ ts,ps,beta,betaVar = L.association(x,REML=REML,returnBeta=True)
+ result.append(formatResult(id,beta,np.sqrt(betaVar).sum(),ts,ps))
+ # compute_snp.q.put([j,formatResult(id,beta,np.sqrt(betaVar).sum(),ts,ps)])
+ # print [j,result[0]]," in result queue\n"
+ if not q:
+ q = compute_snp.q
+ q.put([j,result])
+ return j
+ # PS.append(ps)
+ # TS.append(ts)
+ # return len(result)
+ # compute.q.put(result)
+ # return None
+
+def f_init(q):
+ compute_snp.q = q
+
+def gwas(Y,G,K,restricted_max_likelihood=True,refit=False,verbose=True):
+ """
+ Execute a GWAS. The G matrix should be n inds (cols) x m snps (rows)
+ """
+ matrix_initialize()
+ cpu_num = mp.cpu_count()
+ numThreads = 1
+ kfile2 = False
+
+ sys.stderr.write(str(G.shape)+"\n")
+ n = G.shape[1] # inds
+ inds = n
+ m = G.shape[0] # snps
+ snps = m
+ sys.stderr.write(str(m)+" SNPs\n")
+ # print "***** GWAS: G",G.shape,G
+ assert m>n, "n should be larger than m (snps>inds)"
+
+ # CREATE LMM object for association
+ # if not kfile2: L = LMM(Y,K,Kva,Kve,X0,verbose=verbose)
+ # else: L = LMM_withK2(Y,K,Kva,Kve,X0,verbose=verbose,K2=K2)
+
+ runlmm = lmm.LMM(Y,K) # ,Kva,Kve,X0,verbose=verbose)
+ if not refit:
+ if verbose: sys.stderr.write("Computing fit for null model\n")
+ runlmm.fit() # follow GN model in run_other
+ if verbose: sys.stderr.write("\t heritability=%0.3f, sigma=%0.3f\n" % (runlmm.optH,runlmm.optSigma))
+
+ # outFile = "test.out"
+ # out = open(outFile,'w')
+ out = sys.stderr
+
+ def outputResult(id,beta,betaSD,ts,ps):
+ out.write(formatResult(id,beta,betaSD,ts,ps))
+ def printOutHead(): out.write("\t".join(["SNP_ID","BETA","BETA_SD","F_STAT","P_VALUE"]) + "\n")
+ def formatResult(id,beta,betaSD,ts,ps):
+ return "\t".join([str(x) for x in [id,beta,betaSD,ts,ps]]) + "\n"
+
+ printOutHead()
+
+ # Set up the pool
+ # mp.set_start_method('spawn')
+ q = mp.Queue()
+ p = mp.Pool(numThreads, f_init, [q])
+ collect = []
+
+ # Buffers for pvalues and t-stats
+ # PS = []
+ # TS = []
+ count = 0
+
+ completed = 0
+ last_j = 0
+ # for snp_id in G:
+ for snp in G:
+ print snp.shape,snp
+ snp_id = ('SNPID',snp)
+ count += 1
+ if count % 1000 == 0:
+ job = count/1000
+ if verbose:
+ sys.stderr.write("Job %d At SNP %d\n" % (job,count))
+ if numThreads == 1:
+ compute_snp(job,collect,q)
+ collect = []
+ j,lines = q.get()
+ if verbose:
+ sys.stderr.write("Job "+str(j)+" finished\n")
+ for line in lines:
+ out.write(line)
+ else:
+ p.apply_async(compute_snp,(job,collect))
+ collect = []
+ while job > completed:
+ try:
+ j,lines = q.get_nowait()
+ if verbose:
+ sys.stderr.write("Job "+str(j)+" finished\n")
+ for line in lines:
+ out.write(line)
+ completed += 1
+ except Queue.Empty:
+ pass
+ if job > completed + cpu_num + 5:
+ time.sleep(1)
+ else:
+ if job >= completed:
+ break
+
+ collect.append(snp_id)
+
+ if not numThreads or numThreads > 1:
+ for job in range(int(count/1000)-completed):
+ j,lines = q.get(True,15) # time out
+ if verbose:
+ sys.stderr.write("Job "+str(j)+" finished\n")
+ for line in lines:
+ out.write(line)
+
+ # print collect
+ ps = [item[1][3] for item in collect]
+ ts = [item[1][2] for item in collect]
+ print ps
+ return ts,ps
diff --git a/wqflask/wqflask/my_pylmm/pyLMM/kinship.py b/wqflask/wqflask/my_pylmm/pyLMM/kinship.py
index cd2445f1..00f48939 100644
--- a/wqflask/wqflask/my_pylmm/pyLMM/kinship.py
+++ b/wqflask/wqflask/my_pylmm/pyLMM/kinship.py
@@ -26,7 +26,6 @@ import multiprocessing as mp # Multiprocessing is part of the Python stdlib
import Queue
import time
-
from optmatrix import matrix_initialize, matrixMultT
def kinship_full(G):
@@ -87,12 +86,13 @@ def kinship(G,computeSize=1000,numThreads=None,useBLAS=False,verbose=True):
m = G.shape[0] # snps
snps = m
sys.stderr.write(str(m)+" SNPs\n")
- assert m>n, "n should be larger than m (snps>inds)"
+ assert snps>inds, "snps should be larger than inds (%i snps, %i inds)" % (snps,inds)
q = mp.Queue()
p = mp.Pool(numThreads, f_init, [q])
cpu_num = mp.cpu_count()
print "CPU cores:",cpu_num
+ print snps,computeSize
iterations = snps/computeSize+1
# if testing:
# iterations = 8
diff --git a/wqflask/wqflask/my_pylmm/pyLMM/lmm.py b/wqflask/wqflask/my_pylmm/pyLMM/lmm.py
index 9fd05b42..8c6d3c3c 100644
--- a/wqflask/wqflask/my_pylmm/pyLMM/lmm.py
+++ b/wqflask/wqflask/my_pylmm/pyLMM/lmm.py
@@ -51,6 +51,7 @@ from utility.benchmark import Bench
from utility import temp_data
from kinship import kinship, kinship_full, kvakve
import genotype
+import gwas
try:
from wqflask.my_pylmm.pyLMM import chunks
@@ -253,7 +254,7 @@ def human_association(snp,
# refit=False,
# temp_data=None):
-def run_other(pheno_vector,
+def run_other_old(pheno_vector,
genotype_matrix,
restricted_max_likelihood=True,
refit=False,
@@ -269,7 +270,7 @@ def run_other(pheno_vector,
"""
- print("In run_other")
+ print("In run_other (old)")
print("REML=",restricted_max_likelihood," REFIT=",refit)
with Bench("Calculate Kinship"):
kinship_matrix,genotype_matrix = calculate_kinship(genotype_matrix, tempdata)
@@ -277,9 +278,51 @@ def run_other(pheno_vector,
print("kinship_matrix: ", pf(kinship_matrix))
print("kinship_matrix.shape: ", pf(kinship_matrix.shape))
+ # with Bench("Create LMM object"):
+ # lmm_ob = LMM(pheno_vector, kinship_matrix)
+
+ # with Bench("LMM_ob fitting"):
+ # lmm_ob.fit()
+
+ print("genotype_matrix: ", genotype_matrix.shape)
+ print(genotype_matrix)
+
+ with Bench("Doing GWAS"):
+ t_stats, p_values = GWAS(pheno_vector,
+ genotype_matrix,
+ kinship_matrix,
+ restricted_max_likelihood=True,
+ refit=False,
+ temp_data=tempdata)
+ Bench().report()
+ return p_values, t_stats
+
+def run_other_new(pheno_vector,
+ genotype_matrix,
+ restricted_max_likelihood=True,
+ refit=False,
+ tempdata=None # <---- can not be None
+ ):
+
+ """Takes the phenotype vector and genotype matrix and returns a set of p-values and t-statistics
+
+ restricted_max_likelihood -- whether to use restricted max likelihood; True or False
+ refit -- whether to refit the variance component for each marker
+ temp_data -- TempData object that stores the progress for each major step of the
+ calculations ("calculate_kinship" and "GWAS" take the majority of time)
+
+ """
+
+ print("In run_other (new)")
+ print("REML=",restricted_max_likelihood," REFIT=",refit)
+ with Bench("Calculate Kinship"):
+ kinship_matrix,genotype_matrix = calculate_kinship(genotype_matrix, tempdata)
+
+ print("kinship_matrix: ", pf(kinship_matrix))
+ print("kinship_matrix.shape: ", pf(kinship_matrix.shape))
+
with Bench("Create LMM object"):
lmm_ob = LMM(pheno_vector, kinship_matrix)
-
with Bench("LMM_ob fitting"):
lmm_ob.fit()
@@ -287,15 +330,15 @@ def run_other(pheno_vector,
print(genotype_matrix)
with Bench("Doing GWAS"):
- t_stats, p_values = GWAS(pheno_vector,
- genotype_matrix,
- kinship_matrix,
- restricted_max_likelihood=True,
- refit=False,
- temp_data=tempdata)
+ t_stats, p_values = gwas.gwas(pheno_vector,
+ genotype_matrix.T,
+ kinship_matrix,
+ restricted_max_likelihood=True,
+ refit=False,verbose=True)
Bench().report()
return p_values, t_stats
+run_other = run_other_old
def matrixMult(A,B):
@@ -821,4 +864,3 @@ if __name__ == '__main__':
print("Run from runlmm.py instead")
-
diff --git a/wqflask/wqflask/my_pylmm/pyLMM/runlmm.py b/wqflask/wqflask/my_pylmm/pyLMM/runlmm.py
index cef0cdc4..f17f1bd1 100644
--- a/wqflask/wqflask/my_pylmm/pyLMM/runlmm.py
+++ b/wqflask/wqflask/my_pylmm/pyLMM/runlmm.py
@@ -21,7 +21,7 @@ from optparse import OptionParser
import sys
import tsvreader
import numpy as np
-from lmm import gn2_load_redis, calculate_kinship
+from lmm import gn2_load_redis, calculate_kinship_old
from kinship import kinship, kinship_full
import genotype
import phenotype
@@ -151,17 +151,17 @@ elif cmd == 'kinship':
gnt = None
if options.test_kinship:
- K = kinship_full(G)
+ K = kinship_full(np.copy(G))
print "Genotype",G.shape, "\n", G
print "first Kinship method",K.shape,"\n",K
k1 = round(K[0][0],4)
- K2 = calculate_kinship(np.copy(G.T),temp_data=None)
+ K2,G = calculate_kinship_old(np.copy(G).T,temp_data=None)
print "Genotype",G.shape, "\n", G
print "GN2 Kinship method",K2.shape,"\n",K2
k2 = round(K2[0][0],4)
print "Genotype",G.shape, "\n", G
- K3 = kinship(np.copy(G),options)
+ K3 = kinship(G.T)
print "third Kinship method",K3.shape,"\n",K3
sys.stderr.write(options.geno+"\n")
k3 = round(K3[0][0],4)