def test_score_residues(self):
rule = HCVR("SCORE FROM ( 100G => 10, 101D => 20 )")
expected_residue = repr({Mutation('S100G')})
result = rule.dtree(VariantCalls("S100G R101d"))
self.assertEqual(expected_residue, repr(result.residues))
def test_score_comment(self):
rule = HCVR(
'SCORE FROM (100G => 10, 200T => 3, 100S => "flag1 with_space")')
self.assertEqual(rule(VariantCalls("100G 200d")), 10)
result = rule.dtree(VariantCalls("100S 200T"))
self.assertEqual(result.score, 3)
self.assertIn("flag1 with_space", result.flags)
def test_bool_constants(self):
rule = HCVR("TRUE OR 1G")
self.assertEqual(rule(VariantCalls("1d")), True)
rule = HCVR("FALSE AND 1G")
self.assertEqual(rule(VariantCalls("1G")), False)
rule = HCVR("TRUE OR (FALSE AND TRUE)")
self.assertEqual(rule(VariantCalls("1G")), True)
def test_true_positive(self):
m = VariantCalls('Q54H 444H')
rule = HCVR("SCORE FROM ( 54H => 0, 444H => 8 )")
dtree = rule.dtree(m)
expected_repr = "[Mutation('Q54H'), Mutation('444H')]"
self.assertEqual(expected_repr, repr(sorted(dtree.residues)))
def calculate_component_score(combination, positions):
variants = {} # {pos: mutation_text}
for mutation_text in combination.split('+'):
mutation_text = mutation_text.strip()
mutation_set = MutationSet(mutation_text)
old_mutation_text = variants.get(mutation_set.pos)
if old_mutation_text is not None:
mutation_text = old_mutation_text + ''.join(
m.variant for m in mutation_set.mutations)
variants[mutation_set.pos] = mutation_text
variant_calls = VariantCalls(' '.join(variants.values()))
combination_positions = {}
for mutation_set in variant_calls:
position_scores = positions[mutation_set.pos]
if position_scores:
combination_positions[mutation_set.pos] = position_scores
if not combination_positions:
return 0
score_formula = build_score_formula(combination_positions)
try:
rule = HCVR(score_formula)
except Exception as ex:
raise ValueError('Bad formula for {}.'.format(combination)) from ex
component_score = rule(variant_calls)
return component_score
def parse_rule(rule_text):
rule = HCVR(rule_text)
assert isinstance(rule.dtree, AsiScoreCond), repr(rule.dtree)
score_list = rule.dtree.children[0]
assert isinstance(score_list, ScoreList), repr(score_list)
mutations = defaultdict(list)
for score_expr in score_list.children:
assert isinstance(score_expr, ScoreExpr)
children = score_expr.children
if len(children) == 4:
# Flag
mutation, _, flag, _ = children
display = flag
elif len(children) == 2:
# Numeric score
mutation, score = children
display = score
else:
raise ValueError(
'Unexpected score expression: {!r}'.format(children))
if isinstance(mutation, BoolTrue):
mutation = 'TRUE'
else:
mutation = str(mutation.mutations)
mutations[display].append(mutation)
return mutations
def test_bool_or(self):
rule = HCVR("1G OR (2T OR 7Y)")
self.assertTrue(rule(VariantCalls("1d 2T 7d")))
self.assertFalse(rule(VariantCalls("1d 2d 7d")))
self.assertTrue(rule(VariantCalls("1G 2d 7d")))
with self.assertRaisesRegex(MissingPositionError,
r"Missing position 1"):
rule([])
def test_bool_and(self):
rule = HCVR("1G AND (2T AND 7Y)")
self.assertEqual(rule(VariantCalls("2T 7Y 1G")), True)
self.assertEqual(rule(VariantCalls("2T 7d 1G")), False)
self.assertEqual(rule(VariantCalls("7Y 1G 2T")), True)
with self.assertRaisesRegex(MissingPositionError,
r"Missing position 1"):
rule([])
def test_score_from(self):
rule = HCVR("SCORE FROM ( 100G => 5, 101DST => 20 )")
self.assertEqual(rule(VariantCalls("100G 101G")), 5)
self.assertEqual(rule(VariantCalls("100G 101d")), 5)
self.assertEqual(rule(VariantCalls("100G 101D")), 25)
self.assertEqual(rule(VariantCalls("100G 101DST")), 25)
with self.assertRaisesRegex(MissingPositionError,
r'Missing position 100.'):
rule(VariantCalls("105G 106DST"))
def test_parse_exception(self):
expected_error_message = (
"Error in HCVR: SCORE FROM ( 10R => 2>!<;0 ) (at char 21), (line:1, col:22)"
)
with self.assertRaises(ParseException) as context:
HCVR("SCORE FROM ( 10R => 2;0 )")
self.assertEqual(expected_error_message, str(context.exception))
def test_stanford_rest(self):
examples = [
"SCORE FROM (65R => 20, 74V => 20, 184VI => 20)",
"151M AND EXCLUDE 69i", "215F OR 215Y",
"SCORE FROM (101P => 40, 101E => 30, 101HN => 15, 101Q => 5 )",
"SCORE FROM ( MAX (101P => 40, 101E => 30, 101HN => 15, 101Q => 5 ))",
"(184V AND 115F) => 20"
"3N AND 9N", "2N OR 9N AND 2N", "3N AND (2N AND (4N OR 2N))"
]
for ex in examples:
x = HCVR(ex)
self.assertEqual(ex, x.rule)
def test_parse_exception_multiline(self):
rule = """\
SCORE FROM (
10R => 2;0
)
"""
expected_error_message = (
"Error in HCVR: 10R => 2>!<;0 (at char 25), (line:2, col:13)")
with self.assertRaises(ParseException) as context:
HCVR(rule)
self.assertEqual(expected_error_message, str(context.exception))
def test_chained_and(self):
rule = HCVR("""
SCORE FROM(41L => 5, 62V => 5, MAX ( 65E => 10, 65N =>
30, 65R => 45 ), MAX ( 67E => 5, 67G => 5, 67H => 5, 67N => 5, 67S =>
5, 67T => 5, 67d => 30 ), 68d => 15, MAX ( 69G => 10, 69i => 60, 69d =>
15 ), MAX ( 70E => 15, 70G => 15, 70N => 15, 70Q => 15, 70R => 5, 70S
=> 15, 70T => 15, 70d => 15 ), MAX ( 74I => 30, 74V => 30 ), 75I => 5,
77L => 5, 115F => 60, 116Y => 10, MAX ( 151L => 30, 151M => 60 ), MAX(
184I => 15, 184V => 15 ), 210W => 5, MAX ( 215A => 5, 215C => 5, 215D
=> 5, 215E => 5, 215F => 10, 215I => 5, 215L => 5, 215N => 5, 215S =>
5, 215V => 5, 215Y => 10 ), MAX ( 219E => 5, 219N => 5, 219Q => 5, 219R
=> 5 ), (40F AND 41L AND 210W AND 215FY) => 5, (41L AND 210W) => 10,
(41L AND 210W AND 215FY) => 5, (41L AND 44AD AND 210W AND 215FY) => 5,
(41L AND 67EGN AND 215FY) => 5, (67EGN AND 215FY AND 219ENQR) => 5,
(67EGN AND 70R AND 184IV AND 219ENQR) => 20, (67EGN AND 70R AND
219ENQR) => 10, (70R AND 215FY) => 5, (74IV AND 184IV) => 15, (77L AND
116Y AND 151M) => 10, MAX ((210W AND 215ACDEILNSV) => 5, (210W AND
215FY) => 10), MAX ((41L AND 215ACDEILNSV) => 5, (41L AND 215FY) =>
15))
""")
self.assertEqual(rule(add_mutations("40F 41L 210W 215Y")), 65)
self.assertEqual(rule(add_mutations("41L 210W 215F")), 60)
self.assertEqual(rule(add_mutations("40F 210W 215Y")), 25)
self.assertEqual(rule(add_mutations("40F 67G 215Y")), 15)
def test_score_negate(self):
rule = HCVR("SCORE FROM ( 100!G => 10, 101!SD => 20 )")
self.assertEqual(rule(VariantCalls("100G 101D")), 0)
self.assertEqual(rule(VariantCalls("100S 101S")), 10)
self.assertEqual(rule(VariantCalls("100S 101W")), 30)
self.assertEqual(rule(VariantCalls("100G 101TW")), 20)
def test_asi2_compat(self):
q = "SCORE FROM ( 98G => 10, 100I => 40,\
MAX (101P => 40, 101E => 30, 101HN => 15, 101Q => 5) )"
HCVR(q)
def test_stanford_ex1(self):
HCVR("151M OR 69i")
def test_score_from_min_neg(self):
rule = HCVR("SCORE FROM (MIN (100G => -10, 101D => -20, 102D => 30))")
self.assertEqual(-20, rule(VariantCalls("100G 101D 102d")))
def test_atleast_false(self):
rule = HCVR("SELECT ATLEAST 2 FROM (41L, 67N, 70R, 210W, 215F, 219Q)")
self.assertFalse(rule(VariantCalls('41L 67d 70d 210d 215d 219d')))
def test_hivdb_rules_parse(self):
folder = os.path.dirname(__file__)
rules_file = os.path.join(folder, 'HIVDB.rules')
for line in open(rules_file):
r = HCVR(line)
self.assertEqual(line, r.rule)
def test_select_from_atleast(self):
rule = HCVR("SELECT ATLEAST 2 FROM (2T, 7Y, 3G)")
self.assertTrue(rule(VariantCalls("2T 7Y 3d")))
self.assertFalse(rule(VariantCalls("2T 7d 3d")))
self.assertTrue(rule(VariantCalls("3G 7d 2T")))
def test_atleast_missing(self):
rule = HCVR("SELECT ATLEAST 2 FROM (41L, 67N, 70R, 210W, 215F, 219Q)")
with self.assertRaisesRegex(MissingPositionError,
r'Missing position 70.'):
rule(VariantCalls('41L 67N'))
def test_score_from_max(self):
rule = HCVR("SCORE FROM (MAX (100G => 10, 101D => 20, 102D => 30))")
self.assertEqual(rule(VariantCalls("100G 101D 102d")), 20)
def test_stanford_ex3(self):
HCVR(
"SELECT ATLEAST 2 AND NOTMORETHAN 2 FROM (41L, 67N, 70R, 210W, 215FY, 219QE)"
)
def interpret(self, aaseq, region):
result = AsiResult()
raw_mutations = defaultdict(set)
result.alg_name = self.alg_name
result.alg_version = self.alg_version
drug_classes = self.gene_def.get(region, {})
default_level = ResistanceLevels.FAIL.level
default_level_name = self.level_def[str(default_level)]
mutations = VariantCalls(reference=self.stds[region], sample=aaseq)
for drug_class in drug_classes:
for drug_code in self.drug_class[drug_class]:
drug_name, drug_rules = self.drugs[drug_code]
drug_result = AsiDrugResult()
drug_result.code = drug_code
drug_result.name = drug_name
drug_result.level = default_level
drug_result.level_name = default_level_name
drug_result.drug_class = drug_class
for condition, actions in drug_rules:
rule = HCVR(condition)
try:
rule_result = rule.dtree(mutations)
score = float(rule_result.score)
flags = rule_result.flags
# rule_result.residues doesn't always have wild types.
m = {
mutation
for mutation_set in mutations
for mutation in mutation_set
if mutation in rule_result.residues
}
raw_mutations[drug_class] |= m
for action, comment in actions:
if action == 'level':
if int(comment) > drug_result.level:
drug_result.level = int(comment)
drug_result.level_name = self.level_def[
comment]
elif action == 'comment':
comment, _ = self.comment_def[comment]
while (re.search('\$numberOfMutsIn{', comment)
or re.search('\$listMutsIn{', comment)):
comment = self.comment_filter(
comment, aaseq, region)
drug_result.comments.append(comment)
elif action == 'scorerange':
drug_result.score = score
scorerange = comment
if scorerange == 'useglobalrange':
scorerange = self.global_range
if score == 0 and flags:
if 'Not available' in flags:
drug_result.level = ResistanceLevels.NA.level
elif 'Not indicated' in flags:
drug_result.level = ResistanceLevels.NOT_INDICATED.level
elif 'Effect unknown' in flags:
drug_result.level = ResistanceLevels.UNKNOWN_MUTATIONS.level
else:
# use score range to determine level
for low_score, high_score, level in scorerange:
if low_score == '-INF':
low_score = -99999 # that is close enough to negative infinity.
else:
low_score = float(low_score)
if high_score == 'INF':
high_score = 99999 # that is close enough to infinity.
else:
high_score = float(high_score)
if low_score <= drug_result.score <= high_score:
if int(level) > drug_result.level:
drug_result.level = int(level)
break
except MissingPositionError:
drug_result.level = ResistanceLevels.FAIL.level
drug_result.level_name = self.level_def[str(
drug_result.level)]
result.drugs.append(drug_result)
for cls, cls_mutations in raw_mutations.items():
result.mutations[cls] = [str(m) for m in cls_mutations]
result.drugs.sort(key=lambda e: e.code)
result.drugs.sort(key=lambda e: e.drug_class, reverse=True)
# comments
for target_region, results in self.mutation_comments:
if target_region != region:
continue
for cond, actions in results:
# This evaluates comment rules.
# Previous evaluation was scoring rules.
rule = HCVR(cond)
try:
scoring = rule(mutations)
if scoring:
for _, act in actions:
comment_template, _ = self.comment_def[act]
comment = self.comment_filter(
comment_template, aaseq, region)
result.mutation_comments.append(comment)
except MissingPositionError:
pass
return result
def test_stanford_ex4(self):
HCVR("215FY AND 184!VI")
def interpret(self, aaseq, region):
result = AsiResult()
raw_mutations = defaultdict(set)
result.alg_name = self.alg_name
result.alg_version = self.alg_version
drug_classes = self.gene_def.get(region, {})
default_level = HcvResistanceLevels.FAIL.level
default_level_name = self.level_def[str(default_level)]
mutations = VariantCalls(reference=self.stds[region], sample=aaseq)
for drug_class in drug_classes:
for drug_code in self.drug_class[drug_class]:
drug_name, drug_rules = self.drugs[drug_code]
drug_result = AsiDrugResult()
drug_result.code = drug_code
drug_result.name = drug_name
drug_result.level = default_level
drug_result.level_name = default_level_name
drug_result.drug_class = drug_class
for condition, actions in drug_rules:
rule = HCVR(condition)
try:
rule_result = rule.dtree(mutations)
score = float(rule_result.score)
flags = rule_result.flags
# rule_result.residues doesn't always have wild types.
m = {mutation
for mutation_set in mutations
for mutation in mutation_set
if mutation in rule_result.residues}
raw_mutations[drug_class] |= m
for action, comment in actions:
if action == 'level':
if int(comment) > drug_result.level:
drug_result.level = int(comment)
drug_result.level_name = self.level_def[comment]
elif action == 'comment':
comment, _ = self.comment_def[comment]
while (re.search(r'\$numberOfMutsIn{', comment) or
re.search(r'\$listMutsIn{', comment)):
comment = self.comment_filter(comment, aaseq, region)
drug_result.comments.append(comment)
elif action == 'scorerange':
drug_result.score = score
scorerange = comment
if scorerange == 'useglobalrange':
scorerange = self.global_range
if score == 0 and flags:
if 'Not available' in flags:
drug_result.level = HcvResistanceLevels.NA.level
elif 'Not indicated' in flags:
drug_result.level = HcvResistanceLevels.NOT_INDICATED.level
elif 'Effect unknown' in flags:
drug_result.level = HcvResistanceLevels.UNKNOWN_MUTATIONS.level
else:
# use score range to determine level
for low_score, high_score, level in scorerange:
if low_score == '-INF':
low_score = -99999 # that is close enough to negative infinity.
else:
low_score = float(low_score)
if high_score == 'INF':
high_score = 99999 # that is close enough to infinity.
else:
high_score = float(high_score)
if low_score <= drug_result.score <= high_score:
if int(level) > drug_result.level:
drug_result.level = int(level)
break
except MissingPositionError:
drug_result.level = HcvResistanceLevels.FAIL.level
drug_result.level_name = self.level_def[
str(drug_result.level)]
result.drugs.append(drug_result)
for cls, cls_mutations in raw_mutations.items():
result.mutations[cls] = [str(m) for m in cls_mutations]
result.drugs.sort(key=lambda e: e.code)
result.drugs.sort(key=lambda e: e.drug_class, reverse=True)
# comments
for target_region, results in self.mutation_comments:
if target_region != region:
continue
for cond, actions in results:
# This evaluates comment rules.
# Previous evaluation was scoring rules.
rule = HCVR(cond)
try:
scoring = rule(mutations)
if scoring:
for _, act in actions:
comment_template, _ = self.comment_def[act]
comment = self.comment_filter(comment_template, aaseq, region)
result.mutation_comments.append(comment)
except MissingPositionError:
pass
return result
def test_score_from_exactly(self):
rule = HCVR("SELECT EXACTLY 1 FROM (2T, 7Y)")
score = rule(VariantCalls("2T 7Y 1G"))
self.assertEqual(0, score)