# -*- coding: utf-8 -*-
import numpy as np
from scipy.stats import fisher_exact, hypergeom
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def calc_pvalues(query, gene_sets, background=20000, **kwargs):
"""calculate pvalues for all categories in the graph
:param set query: set of identifiers for which the p value is calculated
:param dict gene_sets: gmt file dict after background was set
:param set background: total number of genes in your annotated database.
:returns: pvalues
x: overlapped gene number
n: length of gene_set which belongs to each terms
hits: overlapped gene names.
For 2*2 contingency table:
=============================================================================
| in query | not in query | row total
=> in gene_set | a | b | a+b
=> not in gene_set | c | d | c+d
column total | a+b+c+d = anno database
=============================================================================
background genes number = a + b + c + d.
Then, in R
x=a the number of white balls drawn without replacement
from an urn which contains both black and white balls.
m=a+b the number of white balls in the urn
n=c+d the number of black balls in the urn
k=a+c the number of balls drawn from the urn
In Scipy:
for args in scipy.hypergeom.sf(k, M, n, N, loc=0):
M: the total number of objects,
n: the total number of Type I objects.
k: the random variate represents the number of Type I objects in N drawn
without replacement from the total population.
Therefore, these two functions are the same when using parameters from 2*2 table:
R: > phyper(x-1, m, n, k, lower.tail=FALSE)
Scipy: >>> hypergeom.sf(x-1, m+n, m, k)
For Odds ratio in Enrichr (see https://maayanlab.cloud/Enrichr/help#background&q=4)
oddsRatio = (1.0 * x * d) / Math.max(1.0 * b * c, 1)
where:
x are the overlapping genes,
b (m-x) are the genes in the annotated set - overlapping genes,
c (k-x) are the genes in the input set - overlapping genes,
d (bg-m-k+x) are the 20,000 genes (or total genes in the background) - genes in the annotated set - genes in the input set + overlapping genes
"""
query = set(query)
vals = []
# background should be all genes in annotated database
# such as go, kegg et.al.
if isinstance(background, set):
bg = len(background) # total number in your annotated database
# filter genes that not found in annotated database
query = query.intersection(background)
elif isinstance(background, int):
bg = background
else:
raise ValueError("background should be set or int object")
# number of genes in your query data
k = len(query)
# pval
subsets = sorted(gene_sets.keys())
for s in subsets:
category = set(gene_sets.get(s))
# the categories should be only exist in custom background too
if isinstance(background, set):
category = category.intersection(background)
hits = query.intersection(category)
x = len(hits) # overlap hits
if x < 1:
continue
m = len(category)
# pVal = hypergeom.sf(hitCount-1,popTotal,bgHits,queryTotal)
# p(X >= hitCounts)
pval = hypergeom.sf(x - 1, bg, m, k)
# oddr, pval2 = odds_ratio_calc(bg, k, m, x)
# expect_count = k*m/bg
# oddr= x / expect_count
# oddr= (x*(bg-m))/(m*(k-x)) # thanks to @sreichl.
oddr = ((x + 0.5) * (bg - m + 0.5)) / (
(m + 0.5) * (k - x + 0.5)
) # Haldane-Anscombe correction, issue #132
vals.append((s, pval, oddr, x, m, hits))
return zip(*vals)
# def odds_ratio_calc(bg_n, gene_list_n, gene_set_n, overlap_n):
# """
# bg_n = number of background genes
# gene_list_n = number of genes in the gene list (ie query genes)
# gene_set_n = number of genes in the (corrected by background) gene set (eg pathways/GO terms)
# overlap_n = number of genes overlapping with between the (corrected by background) gene set and the gene list
# """
# # make contingency table
# table=np.array([[gene_set_n, bg_n-gene_set_n],[overlap_n, gene_list_n-overlap_n]])
# # perform Fisher's exact test
# oddsratio, pvalue = fisher_exact(table)
# # return (inverse) oddsratio
# return 1/oddsratio, pvalue
def _ecdf(x):
nobs = len(x)
return np.arange(1, nobs + 1) / float(nobs)
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def fdrcorrection(pvals, alpha=0.05):
"""benjamini hocheberg fdr correction. inspired by statsmodels"""
# Implement copy from GOATools.
pvals = np.asarray(pvals)
pvals_sortind = np.argsort(pvals)
pvals_sorted = np.take(pvals, pvals_sortind)
ecdffactor = _ecdf(pvals_sorted)
reject = pvals_sorted <= ecdffactor * alpha
if reject.any():
rejectmax = max(np.nonzero(reject)[0])
reject[:rejectmax] = True
pvals_corrected_raw = pvals_sorted / ecdffactor
pvals_corrected = np.minimum.accumulate(pvals_corrected_raw[::-1])[::-1]
del pvals_corrected_raw
pvals_corrected[pvals_corrected > 1] = 1
pvals_corrected_ = np.empty_like(pvals_corrected)
pvals_corrected_[pvals_sortind] = pvals_corrected
del pvals_corrected
reject_ = np.empty_like(reject)
reject_[pvals_sortind] = reject
return reject_, pvals_corrected_
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def multiple_testing_correction(ps, alpha=0.05, method="benjamini-hochberg", **kwargs):
"""correct pvalues for multiple testing and add corrected `q` value
:param ps: list of pvalues
:param alpha: significance level default : 0.05
:param method: multiple testing correction method [bonferroni|benjamini-hochberg]
:returns (q, rej): two lists of q-values and rejected nodes
"""
# Implement copy from GOATools.
_p = np.array(ps)
q = _p.copy()
rej = _p.copy()
mask = ~np.isnan(_p)
p = _p[mask]
if method == "bonferroni":
q[mask] = p * len(p)
rej[mask] = q[mask] < alpha
elif method == "benjamini-hochberg":
_rej, _q = fdrcorrection(p, alpha)
rej[mask] = _rej
q[mask] = _q
else:
raise ValueError(method)
return q, rej