def get_raw_references(datapath, phenotype_set):
"""Parse a phenotype file and collect descriptions and raw phenotypes
raw phenotypes are phenotypes in the original ontology
Args:
datapath path to phenotab file
phenotype_set set of acceptable phenotypes
Returns:
two objects
- dict mapping reference codes to reference descriptions and phenotypes
- set of phenotypes that could not be mapped
"""
badphenotypes = set()
references = dict()
with open_file(datapath, "rt") as f:
reader = csv.DictReader(f, delimiter="\t", quotechar="\"")
for row in reader:
if not valid_reference_id(row["Reference"]):
continue
phenotype = row["Phenotype"]
if phenotype not in phenotype_set:
badphenotypes.add(phenotype)
continue
rowval = tofreq[row["Frequency"]]
id = row["Source"] + ":" + row["Disease_number"]
if id not in references:
references[id] = Representation(name=id)
references[id].title = row["Disease_title"]
references[id].set(phenotype, rowval)
return references, badphenotypes
def test_impute_fromseeds_highfirst(self):
"""imputing values from manually-specified seeds."""
rr = Representation(dict())
# specify data for two children, DOID:4 is higher in tree, so should gain
rr.set("DOID:0014667", 0.4)
rr.set("DOID:0080015", 0.3)
rr.impute(self.obo,
self.obodef,
seeds=["DOID:0014667", "DOID:0080015"])
self.assertAlmostEqual(rr.get("DOID:0014667"),
0.4,
msg="should remain")
self.assertAlmostEqual(rr.get("DOID:0080015"),
0.3,
msg="should remain")
self.assertAlmostEqual(
rr.get("DOID:4"),
1 - ((1 - 0.4) * (1 - 0.3) * (1 - 0.2)),
msg="ancestor gains from two children (and prior)")
self.assertAlmostEqual(rr.get("DOID:655"),
0.2,
msg="remain; new DOID:4")
def setUpClass(cls):
"""For setup, ensure db does not exist."""
config = CompleteTestConfig()
config.null_prior = 0.2
cls.dbfile = config.db
cls.pipeline = Phenoscoring(config)
cls.pipeline.build()
obopath = check_file(config.obo, config.db, "obo")
cls.obo = MinimalObo(obopath, True)
# a dummy set of default values
cls.obodefaults = dict.fromkeys(cls.obo.ids(), 0.2)
cls.obozeros = dict.fromkeys(cls.obo.ids(), 0)
cls.ref_priors = get_ref_priors(config.db)
cls.rs, cls.rs2 = get_refsets(config.db, ref_priors=cls.ref_priors)
cls.rs.learn_obo(cls.obo)
cls.rs2.learn_obo(cls.obo)
# for testing individual configurations
cls.y3model = Representation(name="Y3").set("Y:003", 0.8)
cls.refA = Representation(name="refA").set("Y:002", 1)
cls.refA.defaults(cls.obozeros)
cls.refB = Representation(name="refB").set("Y:002", 1)
cls.refB.defaults(cls.obozeros)
def setUpClass(cls):
# create with sibling diseases Y:002 and Y:001 are siblings
# set some phenotype priors that are nonzero
cls.priors = dict()
cls.priors["Y:004"] = 0.66
cls.priors["Y:005"] = cls.priors["Y:006"] = 0.25
cls.priors["Y:003"] = 0.66
cls.priors["Y:001"] = cls.priors["Y:002"] = 0.33
cls.priors["Y:007"] = cls.priors["Y:008"] = 0.25
cls.refnull = Representation(name="null")
# refA has a negative phenotype
cls.refA = Representation(name="refA")
cls.refA.set("Y:002", 0.1).impute(Yobo, cls.priors)
# refB has a negative and positive phenotypes
cls.refB = Representation(name="refB")
cls.refB.set("Y:001", 0.01).set("Y:006", 0.8).impute(Yobo, cls.priors)
# refB2 has a weaker positive phenotype
cls.refB2 = Representation(name="refB2")
cls.refB2.set("Y:001", 0.1).set("Y:006", 0.5).impute(Yobo, cls.priors)
cls.rs = ReferenceSet(dict(null=0.4, refA=0.3, refB=0.3, refB2=0.3),
ids=Yobo.ids(),
row_priors=cls.priors)
cls.rs.add(cls.refnull).add(cls.refA).add(cls.refB).add(cls.refB2)
cls.rs.learn_obo(Yobo)
def setUpClass(cls):
# set some phenotype priors that are nonzero
cls.priors = dict()
cls.priors["Y:004"] = 0.66
cls.priors["Y:005"] = cls.priors["Y:006"] = 0.25
cls.priors["Y:003"] = 0.66
cls.priors["Y:001"] = cls.priors["Y:002"] = 0.33
cls.priors["Y:007"] = cls.priors["Y:008"] = 0.25
# create reference set with some strong phenotypes
cls.refnull = Representation(name="null")
cls.refA = Representation(name="refA")
cls.refB = Representation(name="refB")
cls.refA.set("Y:002", 1).impute(Yobo, cls.priors)
cls.refB = Representation(name="refB")
cls.refB.set("Y:001", 1).impute(Yobo, cls.priors)
# reset missing phenotypes to smaller-than-prior
for k, v in cls.priors.items():
if cls.refA.get(k) == v:
cls.refA.set(k, v / 2)
if cls.refB.get(k) == v:
cls.refB.set(k, v / 2)
cls.rs = ReferenceSet(dict(null=0.3, refA=0.3, refB=0.3),
ids=Yobo.ids(),
row_priors=cls.priors)
cls.rs.add(cls.refnull).add(cls.refA).add(cls.refB)
cls.rs.learn_obo(Yobo)
def test_bg_nonverbose(self):
"""compute with background value leaves score the same."""
neutral = Representation(name="TP")
neutral.set("Y:004", self.priors["Y:004"])
chain = self.rs.inference_chain(neutral, "refA", verbose=False)
chain.evaluate()
self.assertEqual(chain.posterior, chain.prior)
def get_complete_null(dbpath):
"""create a complete representation for the null reference"""
result = Representation(name="null")
tab = ReferenceCompletePhenotypeTable(dbpath)
generator = DBGenerator(tab, where=dict(id="null"))
for row in generator.next():
result.set(row["phenotype"], row["value"])
return result
def test_FP_same_parent(self):
"""various FPs to same parent score the same"""
# both models are FP using children of a refA phenotype
FP_close = Representation(name="close").set("Y:007", 0.9)
FP_far = Representation(name="far").set("Y:008", 0.9)
chain_close = self.rs.inference_chain(FP_close, "refA", verbose=True)
chain_far = self.rs.inference_chain(FP_far, "refA", verbose=True)
chain_close.evaluate()
chain_far.evaluate()
self.assertEqual(chain_close.posterior, chain_far.posterior)
def get_concise_refdict(dbpath):
"""transfer information on concise reference phenotypes into a dict."""
refdict = dict()
refdict["null"] = Representation(name="null")
refgenerator = DBGenerator(ReferenceConcisePhenotypeTable(dbpath))
for row in refgenerator.next():
rowid = row["id"]
if rowid not in refdict:
refdict[rowid] = Representation(name=rowid)
refdict[rowid].set(row["phenotype"], row["value"])
return refdict
def test_prep_row_priors(self):
"""prepare row priors."""
# let ref universe have two annotations and one null
refA = Representation(data=dict(a=1), name="refA")
refA.defaults(zerovals)
refB = Representation(data=dict(a=1, b=0.8), name="refB")
refB.defaults(zerovals)
rs = ReferenceSet(dict(refA=0.5, refB=0.5), ids=zerovals.keys())
rs.add(refA).add(refB)
# compute feature priors
rs.prep()
# row_priors should gain key/values for all features
expected_features = set(zerovals.keys())
self.assertEqual(set(rs.row_names), expected_features)
# features declared in representations should get reasonable priors
a_index = rs.rows["a"]
b_index = rs.rows["b"]
d_index = rs.rows["d"]
self.assertEqual(rs.row_priors[a_index], 1,
"refA and refB both have a")
self.assertEqual(rs.row_priors[b_index], 0.4,
"only refB has b, so 0.8/2")
self.assertEqual(rs.row_priors[d_index], 0.2,
"value is 1/num features")
def test_positive_parent_multi(self):
"""fetching a parent term when terms have multiple parents."""
# load an ontology in which Y7 is connected to both Y2 and Y1
Yfile = join(testdir, "Ymulti.obo")
Yobo = MinimalObo(Yfile)
Ydefaults = dict.fromkeys(Yobo.ids(), 0.0001)
Ydefaults["Y:003"] = 0.0002
Ydefaults["Y:005"] = 0.0002
# make slight variations of representations
rs = ReferenceSet(dict(refA=0.5, refB=0.5),
ids=Yobo.ids(),
row_priors=Ydefaults)
refA = Representation(name="refA")
refA.set("Y:002", 0.5).set("Y:005", 1).impute(Yobo, Ydefaults)
refB = Representation(name="refB")
refB.set("Y:001", 0.5).impute(Yobo, Ydefaults)
rs.add(refA).add(refB)
rs.learn_obo(Yobo)
self.assertEqual(
rs._positive_ancestor(rs.columns["refA"], rs.rows["Y:007"]),
rs.rows["Y:002"], "Y2 is a positive ancestor")
self.assertEqual(
rs._positive_ancestor(rs.columns["refB"], rs.rows["Y:007"]),
rs.rows["Y:001"], "Y1 is a positive immediate parent")
def test_FN_decrease_scaled_with_ref(self):
"""negative compared to positive decreases score"""
FN1 = Representation(name="FN1").set("Y:005", 0.01)
chain_FN1 = self.rs.inference_chain(FN1, "refB", verbose=True)
chain_FN1.evaluate_inference()
FN2 = Representation(name="FN2").set("Y:005", 0.01)
chain_FN2 = self.rs.inference_chain(FN2, "refB2", verbose=True)
chain_FN2.evaluate_inference()
# both cases should lead to decrease in score
self.assertLess(chain_FN1.posterior, chain_FN1.prior)
self.assertLess(chain_FN2.posterior, chain_FN2.prior)
# the decrease should be steeper in FN1 because refB positive is stronger
self.assertLess(chain_FN1.posterior, chain_FN2.posterior)
def test_FN_decrease_scales_with_model(self):
"""negative compared to positive decreases score"""
FN1 = Representation(name="FN").set("Y:005", 0.01)
FN2 = Representation(name="FN").set("Y:005", 0.001)
chain_FN1 = self.rs.inference_chain(FN1, "refB", verbose=True)
chain_FN1.evaluate_inference()
chain_FN2 = self.rs.inference_chain(FN2, "refB", verbose=True)
chain_FN2.evaluate_inference()
# both models should decrease score
self.assertLess(chain_FN1.posterior, chain_FN1.prior)
self.assertLess(chain_FN2.posterior, chain_FN2.prior)
# second model should decrease more
self.assertLess(chain_FN2.posterior, chain_FN1.posterior)
def test_FN_can_decrease_score(self):
"""negative compared to positive decreases score"""
FN = Representation(name="FN").set("Y:005", 0.01)
chain_FN = self.rs.inference_chain(FN, "refB", verbose=True)
chain_FN.evaluate_inference()
self.assertLess(chain_FN.posterior, chain_FN.prior)
def test_AN_leaves_score_unchanged(self):
"""negative compared to prior leaves score unchanged """
AN = Representation(name="FN").set("Y:005", 0.01)
chain_AN = self.rs.inference_chain(AN, "refA", verbose=True)
chain_AN.evaluate_inference()
self.assertAlmostEqual(chain_AN.posterior, chain_AN.prior)
def test_empty_representation(self):
"""setting and getting from a generic representation."""
rr = Representation()
self.assertEqual(len(rr.data), 0, "representation should be empty")
self.assertEqual(rr.name, None,
"representation should not have a name")
def test_add_without_name_raises(self):
"""adding a representation without a name raises exceptions."""
r1 = Representation().set("DOID:0014667", 0.4)
rs = ReferenceSet(dict(refA=0.5, refB=0.5), ids=obo.ids())
with self.assertRaises(Exception):
rs.add(r1)
def test_FP2_with_null(self):
"""FP2 is phenotype with a moderate high prior."""
FP2 = Representation(name="model").set("Y:002", 0.9)
chain2 = self.rs.inference_chain(FP2, "null")
chain2.evaluate()
self.assertLessEqual(chain2.posterior, chain2.prior)
def test_FP3_with_null(self):
"""FP3 is phenotype with a fairly high prior."""
FP3 = Representation(name="model").set("Y:003", 0.9)
chain3 = self.rs.inference_chain(FP3, "null", verbose=True)
chain3.evaluate()
self.assertLessEqual(chain3.posterior, chain3.prior)
def test_positive_parent(self):
"""fetching a parent term that has a positive value."""
rs = ReferenceSet(dict(refA=0.5), ids=Yobo.ids(), row_priors=Ydefaults)
refA = Representation(name="refA")
refA.set("Y:002", 0.5).set("Y:005", 1).impute(Yobo, Ydefaults)
rs.add(refA)
rs.learn_obo(Yobo)
refAindex = rs.columns["refA"]
self.assertEqual(rs._positive_ancestor(refAindex, rs.rows["Y:002"]),
rs.rows["Y:002"], "Y2 is itself is positive")
self.assertEqual(rs._positive_ancestor(refAindex, rs.rows["Y:007"]),
rs.rows["Y:002"], "Y2 is immediate parent of Y7")
self.assertEqual(rs._positive_ancestor(refAindex, rs.rows["Y:006"]),
rs.rows["Y:005"], "Y5 is immediate parent of Y6")
def get_model_representations(dbpath,
obo,
log=None,
log_prefix="",
model_names=None):
"""transfer model phenotype data into representations"""
if model_names is None:
model_names = get_model_names(dbpath)
model_names_set = set(model_names)
result = dict()
for m in model_names:
result[m] = Representation(name=m)
phen_priors = get_phenotype_priors(dbpath)
generator = DBGenerator(ModelPhenotypeTable(dbpath))
for row in generator.next():
m, phenotype = row["id"], obo.canonical(row["phenotype"])
# avoid cases - irrelevant model, obsolete phenotype
if m not in model_names_set:
continue
if obo.has(phenotype) and not obo.valid(phenotype):
phenotype = obo.replaced_by(phenotype)
if phenotype is None:
if log is not None:
msg = "Skipping phenotype " + row["phenotype"]
msg += " in model " + m
log(log_prefix + " - " + msg)
continue
result[m] = add_data_to_model(result[m], phenotype, row["value"],
row["TPR"], row["FPR"], phen_priors)
return result
def __init__(self,
config,
references=None,
models=None,
log=None,
run_msg="Packet "):
"""A runnable class for processing a set of references and models
:param config: object of class PhenoscoringConfig
:param references: iterable with reference names
:param models: iterable with model names
:param stamp: timestamp for calculations
:param log: a logging function
:param run_msg: a template for a status message
"""
self.config = config
self.stamp = config.stamp
self.log = log
self.run_msg = run_msg
self.phen_priors = None
self.ref_priors = None
self.general_refset = None
self.specific_refset = None
self.models = dict()
self.references = set()
# setup calculation with references and stub models
self.references = set(references)
for id in models:
self.models[id] = Representation(name=id)
def test_general_representation_get(self):
"""setting and getting from a generic representation."""
rr = Representation(dict(xyz=0.2))
rr.set("bob", 0.4)
rr.set("xyz", 0.3)
rr.defaults(self.defaults)
self.assertEqual(rr.get("bob"), 0.4,
"value should come from manual input")
self.assertEqual(rr.get("abc"), 0.1,
"value should come from defaults dict")
self.assertEqual(rr.get("xyz"), 0.3,
"value should come from manual override")
def test_specific_term_FP_increases(self):
"""score a specific model, vaguely similar disease should increase."""
rr = Representation(name="specific").set("Y:008", 0.8)
inf = self.rs.inference(rr)
self.assertGreater(inf["DISEASE:3"], inf["DISEASE:1"],
"D3 has Y2, which is close to Y1")
def test_refset2_inference(self):
"""inference based on specific should be smaller than on general."""
rr = Representation(name="custom").set("Y:001", 0.8)
inf_general = self.rs.inference(rr)
inf_specific = self.rs2.inference(rr)
# Y:001 is shared by DISEASE:1 and DISEASE:2, so specific inf down
self.assertLess(inf_specific["DISEASE:1"], inf_general["DISEASE:1"])
def test_model_rootonly(self):
"""score a vague model."""
rr = Representation(name="vague").set("Y:004", 0.8)
inf = self.rs.inference(rr)
self.assertAlmostEqual(inf["DISEASE:1"], inf["DISEASE:2"],
"most diseases about the same")
def test_FP7_with_null(self):
"""FP7 is phenotype with a low prior."""
FP7 = Representation(name="model").set("Y:007", 0.9)
chain7 = self.rs.inference_chain(FP7, "null", verbose=True)
chain7.evaluate()
self.assertLess(chain7.posterior, chain7.prior,
"must be strictly lower")
def test_impute_fromseeds_lowfirst(self):
"""imputing values from manually-specified seeds."""
rr = Representation(dict())
## specify an inconsistent set of values, DOID:4 is higher in tree, so cannot
## have a lower value than DOID:0014667
rr.set("DOID:0014667", 0.4).set("DOID:4", 0.1)
rr.impute(self.obo, self.obodef, seeds=["DOID:4", "DOID:0014667"])
self.assertEqual(rr.get("DOID:0080015"), 0.1, "child of DOID:4")
self.assertEqual(rr.get("DOID:655"), 0.1, "child of DOID:4")
def test_general_representation_get2(self):
"""setting and getting from a generic representation."""
# Similar to previous, but setting defaults before the specifics
rr = Representation(dict(abc=0.1, xyz=0.2))
rr.defaults(self.defaults)
rr.set("bob", 0.4)
rr.set("xyz", 0.3)
self.assertEqual(rr.get("bob"), 0.4,
"value should come from manual input")
self.assertEqual(rr.get("abc"), 0.1,
"value should come from defaults dict")
self.assertEqual(rr.get("xyz"), 0.3,
"value should come from manual override")
def test_TN_strong_model(self):
"""TN against strong negative ref should increase overall score"""
# create two models that matches ref phenotypes TN
TNA = Representation(name="model").set("Y:002", 0.01)
TNB = Representation(name="model").set("Y:002", 0.001)
# construct inference chains that give TNs
chainA = self.rs.inference_chain(TNA, "refA", verbose=True)
chainA.evaluate_inference()
chainB = self.rs.inference_chain(TNB, "refA", verbose=True)
chainB.evaluate_inference()
# both comparisons should lead to higher scores
self.assertGreater(chainA.posterior, chainA.prior)
self.assertGreater(chainB.posterior, chainB.prior)
# second comparison should end higher because refB is more strong negative
self.assertGreater(chainB.posterior, chainA.posterior)
