def test_kernel_empty(self):
'''
test trying to run kernel with an empty array
'''
counts = np.array([], dtype=np.float)
size_factors = np.array([], dtype=np.float)
membership = np.empty((0, ), dtype=INT_DTYPE)
rng = kernel.RandomState()
k = kernel.ssea_kernel(counts,
size_factors,
membership,
rng,
resample_counts=True,
permute_samples=True,
add_noise=True,
noise_loc=1.0,
noise_scale=1.0,
method_miss=3,
method_hit=3,
method_param=1.0)
(ranks, norm_counts, norm_counts_miss, norm_counts_hit, es_val,
es_rank, es_run) = k
self.assertTrue(len(ranks) == 0)
self.assertTrue(len(norm_counts) == 0)
self.assertTrue(len(norm_counts_miss) == 0)
self.assertTrue(len(norm_counts_hit) == 0)
self.assertTrue(es_val == 0)
self.assertTrue(es_rank == 0)
self.assertTrue(es_run.shape == (0, ))
def test_kernel_empty(self):
'''
test trying to run kernel with an empty array
'''
counts = np.array([], dtype=np.float)
size_factors = np.array([], dtype=np.float)
membership = np.empty((0,), dtype=INT_DTYPE)
rng = kernel.RandomState()
k = kernel.ssea_kernel(counts, size_factors, membership, rng,
resample_counts=True,
permute_samples=True,
add_noise=True,
noise_loc=1.0,
noise_scale=1.0,
method_miss=3,
method_hit=3,
method_param=1.0)
(ranks, norm_counts, norm_counts_miss, norm_counts_hit,
es_val, es_rank, es_run) = k
self.assertTrue(len(ranks) == 0)
self.assertTrue(len(norm_counts) == 0)
self.assertTrue(len(norm_counts_miss) == 0)
self.assertTrue(len(norm_counts_hit) == 0)
self.assertTrue(es_val == 0)
self.assertTrue(es_rank == 0)
self.assertTrue(es_run.shape == (0,))
def ssea_run(counts, size_factors, membership, rng, config):
'''
counts: numpy array of float values
size_factors: normalization factors for counts
membership: int array (0 or 1) with set membership
rng: RandomState object
config: Config object
'''
# run kernel to generate a range of observed enrichment scores
resample_rand_seeds = np.empty(config.resampling_iterations, dtype=np.int)
resample_count_ranks = np.empty(
(config.resampling_iterations, counts.shape[0]), dtype=np.int)
resample_es_vals = np.zeros(config.resampling_iterations, dtype=np.float)
resample_es_ranks = np.zeros(config.resampling_iterations, dtype=np.int)
for i in xrange(config.resampling_iterations):
# save random number generator seed before running kernel
resample_rand_seeds[i] = rng.seed
k = ssea_kernel(counts,
size_factors,
membership,
rng,
resample_counts=True,
permute_samples=False,
add_noise=True,
noise_loc=config.noise_loc,
noise_scale=config.noise_scale,
method_miss=config.weight_miss,
method_hit=config.weight_hit,
method_param=config.weight_param)
k = KernelResult._make(k)
resample_count_ranks[i] = k.ranks
resample_es_vals[i] = k.es_val
resample_es_ranks[i] = k.es_rank
# find the median ES value
median_index = int(config.resampling_iterations / 2)
median_index = resample_es_vals.argsort()[median_index]
median_es_val = resample_es_vals[median_index]
# choose whether to use the positive or negative side of the
# distribution based on the median ES value
if median_es_val == 0:
return Result.default(), np.zeros((0, ), dtype=np.float)
elif median_es_val < 0:
signfunc = np.less
else:
signfunc = np.greater
# subset to include only the corresponding side of the distribution
resample_sign_inds = signfunc(resample_es_vals, 0)
resample_rand_seeds = resample_rand_seeds[resample_sign_inds]
resample_count_ranks = resample_count_ranks[resample_sign_inds]
resample_es_vals = resample_es_vals[resample_sign_inds]
resample_es_ranks = resample_es_ranks[resample_sign_inds]
# determine the median value
median_index = int(resample_es_vals.shape[0] / 2)
median_index = resample_es_vals.argsort()[median_index]
# select the kernel run representing the median ES value
rand_seed = resample_rand_seeds[median_index]
es_val = resample_es_vals[median_index]
es_rank = resample_es_ranks[median_index]
ranks = resample_count_ranks[median_index]
es_sign = cmp(es_val, 0)
# permute samples and determine ES null distribution
null_es_vals = np.zeros(config.perms, dtype=np.float)
null_es_ranks = np.zeros(config.perms, dtype=np.float)
i = 0
while i < config.perms:
k = ssea_kernel(counts,
size_factors,
membership,
rng,
resample_counts=True,
permute_samples=True,
add_noise=True,
noise_loc=config.noise_loc,
noise_scale=config.noise_scale,
method_miss=config.weight_miss,
method_hit=config.weight_hit,
method_param=config.weight_param)
k = KernelResult._make(k)
if cmp(k.es_val, 0) == es_sign:
null_es_vals[i] = k.es_val
null_es_ranks[i] = k.es_rank
i += 1
# Subset the null ES scores to only positive or negative
null_sign_inds = signfunc(null_es_vals, 0)
null_es_vals = null_es_vals[null_sign_inds]
null_es_ranks = null_es_ranks[null_sign_inds]
# Adjust for variation in gene set size. Normalize ES(S,null)
# and the observed ES(S), separately rescaling the positive and
# negative scores by dividing by the mean of the ES(S,null) to
# yield normalized scores NES(S,null)
null_es_mean = np.fabs(null_es_vals.mean())
null_nes_vals = null_es_vals / null_es_mean
# Normalize the observed ES(S) by rescaling by the mean of
# the ES(S,null) separately for positive and negative ES(S)
nes_val = es_val / null_es_mean
# estimate nominal p value for S from ES(S,null) by using the
# positive or negative portion of the distribution corresponding
# to the sign of the observed ES(S)
p_value = (np.fabs(null_es_vals) >= np.fabs(es_val)).sum().astype(np.float)
p_value /= null_es_vals.shape[0]
# Create result object for this SSEA test
res = Result()
res.rand_seed = int(rand_seed)
res.es = round(es_val, FLOAT_PRECISION)
res.es_rank = int(es_rank)
res.nominal_p_value = round(p_value, SCIENTIFIC_NOTATION_PRECISION)
res.nes = round(nes_val, FLOAT_PRECISION)
# save some of the resampled es points
res.resample_es_vals = np.around(resample_es_vals[:Result.MAX_POINTS],
FLOAT_PRECISION)
res.resample_es_ranks = resample_es_ranks[:Result.MAX_POINTS]
# save null distribution points
res.null_es_mean = null_es_mean
res.null_es_vals = np.around(null_es_vals[:Result.MAX_POINTS],
FLOAT_PRECISION)
res.null_es_ranks = null_es_ranks[:Result.MAX_POINTS]
# get indexes of hits in this set
m = membership[ranks]
hit_inds = (m > 0).nonzero()[0]
num_hits = hit_inds.shape[0]
num_misses = m.shape[0] - num_hits
# calculate leading edge stats
if es_val < 0:
core_hits = sum(i >= es_rank for i in hit_inds)
core_misses = (m.shape[0] - es_rank) - core_hits
else:
core_hits = sum(i <= es_rank for i in hit_inds)
core_misses = 1 + es_rank - core_hits
null_hits = num_hits - core_hits
null_misses = num_misses - core_misses
# fisher exact test (one-sided hypothesis that LE is enricheD)
fisher_p_value = fisher.pvalue(core_hits, core_misses, null_hits,
null_misses).right_tail
# odds ratio
n = np.inf if null_hits == 0 else float(core_hits) / null_hits
d = np.inf if null_misses == 0 else float(core_misses) / null_misses
if np.isfinite(n) and np.isfinite(d):
if n == 0 and d == 0:
odds_ratio = np.nan
else:
odds_ratio = np.inf if d == 0 else (n / d)
elif np.isfinite(d):
odds_ratio = np.inf
else:
odds_ratio = np.nan if n == 0 else 0.0
# create dictionary result
res.core_hits = int(core_hits)
res.core_misses = int(core_misses)
res.null_hits = int(null_hits)
res.null_misses = int(null_misses)
res.fisher_p_value = np.round(fisher_p_value,
SCIENTIFIC_NOTATION_PRECISION)
res.odds_ratio = odds_ratio
# return result and null distribution for subsequent fdr calculations
return res, null_nes_vals
def ssea_run(counts, size_factors, membership, rng, config):
'''
counts: numpy array of float values
size_factors: normalization factors for counts
membership: int array (0 or 1) with set membership
rng: RandomState object
config: Config object
'''
# run kernel to generate a range of observed enrichment scores
resample_rand_seeds = np.empty(config.resampling_iterations, dtype=np.int)
resample_count_ranks = np.empty((config.resampling_iterations, counts.shape[0]), dtype=np.int)
resample_es_vals = np.zeros(config.resampling_iterations, dtype=np.float)
resample_es_ranks = np.zeros(config.resampling_iterations, dtype=np.int)
for i in xrange(config.resampling_iterations):
# save random number generator seed before running kernel
resample_rand_seeds[i] = rng.seed
k = ssea_kernel(counts, size_factors, membership, rng,
resample_counts=True,
permute_samples=False,
add_noise=True,
noise_loc=config.noise_loc,
noise_scale=config.noise_scale,
method_miss=config.weight_miss,
method_hit=config.weight_hit,
method_param=config.weight_param)
k = KernelResult._make(k)
resample_count_ranks[i] = k.ranks
resample_es_vals[i] = k.es_val
resample_es_ranks[i] = k.es_rank
# find the median ES value
median_index = int(config.resampling_iterations / 2)
median_index = resample_es_vals.argsort()[median_index]
median_es_val = resample_es_vals[median_index]
# choose whether to use the positive or negative side of the
# distribution based on the median ES value
if median_es_val == 0:
return Result.default(), np.zeros((0,), dtype=np.float)
elif median_es_val < 0:
signfunc = np.less
else:
signfunc = np.greater
# subset to include only the corresponding side of the distribution
resample_sign_inds = signfunc(resample_es_vals, 0)
resample_rand_seeds = resample_rand_seeds[resample_sign_inds]
resample_count_ranks = resample_count_ranks[resample_sign_inds]
resample_es_vals = resample_es_vals[resample_sign_inds]
resample_es_ranks = resample_es_ranks[resample_sign_inds]
# determine the median value
median_index = int(resample_es_vals.shape[0] / 2)
median_index = resample_es_vals.argsort()[median_index]
# select the kernel run representing the median ES value
rand_seed = resample_rand_seeds[median_index]
es_val = resample_es_vals[median_index]
es_rank = resample_es_ranks[median_index]
ranks = resample_count_ranks[median_index]
es_sign = cmp(es_val, 0)
# permute samples and determine ES null distribution
null_es_vals = np.zeros(config.perms, dtype=np.float)
null_es_ranks = np.zeros(config.perms, dtype=np.float)
i = 0
while i < config.perms:
k = ssea_kernel(counts, size_factors, membership, rng,
resample_counts=True,
permute_samples=True,
add_noise=True,
noise_loc=config.noise_loc,
noise_scale=config.noise_scale,
method_miss=config.weight_miss,
method_hit=config.weight_hit,
method_param=config.weight_param)
k = KernelResult._make(k)
if cmp(k.es_val, 0) == es_sign:
null_es_vals[i] = k.es_val
null_es_ranks[i] = k.es_rank
i += 1
# Subset the null ES scores to only positive or negative
null_sign_inds = signfunc(null_es_vals, 0)
null_es_vals = null_es_vals[null_sign_inds]
null_es_ranks = null_es_ranks[null_sign_inds]
# Adjust for variation in gene set size. Normalize ES(S,null)
# and the observed ES(S), separately rescaling the positive and
# negative scores by dividing by the mean of the ES(S,null) to
# yield normalized scores NES(S,null)
null_es_mean = np.fabs(null_es_vals.mean())
null_nes_vals = null_es_vals / null_es_mean
# Normalize the observed ES(S) by rescaling by the mean of
# the ES(S,null) separately for positive and negative ES(S)
nes_val = es_val / null_es_mean
# estimate nominal p value for S from ES(S,null) by using the
# positive or negative portion of the distribution corresponding
# to the sign of the observed ES(S)
p_value = (np.fabs(null_es_vals) >= np.fabs(es_val)).sum().astype(np.float)
p_value /= null_es_vals.shape[0]
# Create result object for this SSEA test
res = Result()
res.rand_seed = int(rand_seed)
res.es = round(es_val, FLOAT_PRECISION)
res.es_rank = int(es_rank)
res.nominal_p_value = round(p_value, SCIENTIFIC_NOTATION_PRECISION)
res.nes = round(nes_val, FLOAT_PRECISION)
# save some of the resampled es points
res.resample_es_vals = np.around(resample_es_vals[:Result.MAX_POINTS], FLOAT_PRECISION)
res.resample_es_ranks = resample_es_ranks[:Result.MAX_POINTS]
# save null distribution points
res.null_es_mean = null_es_mean
res.null_es_vals = np.around(null_es_vals[:Result.MAX_POINTS], FLOAT_PRECISION)
res.null_es_ranks = null_es_ranks[:Result.MAX_POINTS]
# get indexes of hits in this set
m = membership[ranks]
hit_inds = (m > 0).nonzero()[0]
num_hits = hit_inds.shape[0]
num_misses = m.shape[0] - num_hits
# calculate leading edge stats
if es_val < 0:
core_hits = sum(i >= es_rank for i in hit_inds)
core_misses = (m.shape[0] - es_rank) - core_hits
else:
core_hits = sum(i <= es_rank for i in hit_inds)
core_misses = 1 + es_rank - core_hits
null_hits = num_hits - core_hits
null_misses = num_misses - core_misses
# fisher exact test (one-sided hypothesis that LE is enricheD)
fisher_p_value = fisher.pvalue(core_hits, core_misses, null_hits, null_misses).right_tail
# odds ratio
n = np.inf if null_hits == 0 else float(core_hits) / null_hits
d = np.inf if null_misses == 0 else float(core_misses) / null_misses
if np.isfinite(n) and np.isfinite(d):
if n == 0 and d == 0:
odds_ratio = np.nan
else:
odds_ratio = np.inf if d == 0 else (n / d)
elif np.isfinite(d):
odds_ratio = np.inf
else:
odds_ratio = np.nan if n == 0 else 0.0
# create dictionary result
res.core_hits = int(core_hits)
res.core_misses = int(core_misses)
res.null_hits = int(null_hits)
res.null_misses = int(null_misses)
res.fisher_p_value = np.round(fisher_p_value, SCIENTIFIC_NOTATION_PRECISION)
res.odds_ratio = odds_ratio
# return result and null distribution for subsequent fdr calculations
return res, null_nes_vals
