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Feature/ndrs2 3696 sheffield brca #184

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0fcb8dd
Handling new strings for no scope cases
shilpigoeldev Mar 18, 2026
266181f
new mtype rules
shilpigoeldev Mar 18, 2026
6301e61
test added for mtype changes
shilpigoeldev Mar 18, 2026
0ffd1fb
bug fix parameter name
shilpigoeldev Mar 18, 2026
3796aaa
fixed r208 rule
shilpigoeldev Mar 18, 2026
4cec3a1
handling geno string
shilpigoeldev Mar 19, 2026
2d1e8c5
final changes and tests added
shilpigoeldev Mar 19, 2026
a6abb73
Missing rules and test
shilpigoeldev Mar 19, 2026
9c76776
changed rule to FS
shilpigoeldev Mar 19, 2026
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78 changes: 47 additions & 31 deletions lib/import/brca/providers/sheffield/sheffield_handler.rb
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Original file line number Diff line number Diff line change
Expand Up @@ -71,6 +71,7 @@ def get_genes_set_targeted(record)
@genes_set = []
@genes_set.append(karyo_column.scan(BRCA_REGEX))
@genes_set.append(genotype_column.scan(BRCA_REGEX))
@genes_set.flatten.uniq
end

def process_scope_ovarian_panel(karyo, genotype, _record)
Expand Down Expand Up @@ -126,7 +127,11 @@ def process_scope_r207(karyo, genotype, record)
@logger.debug "ADDED FULL_SCREEN TEST for: #{karyo}"
genotype.add_test_scope(:full_screen)
@genes_set = R207_GENE_MAPPING_FS[karyo]
elsif R207_GENE_MAPPING_TAR.include? karyo
elsif /^R207.1/ix.match(karyo)
@logger.debug "ADDED FULL_SCREEN TEST for: #{karyo}"
genotype.add_test_scope(:full_screen)
@genes_set = R207_1_FS_GENES
elsif /^R240|^R242/ix.match(karyo)
@logger.debug "ADDED TARGETED TEST for: #{karyo}"
genotype.add_test_scope(:targeted_mutation)
get_genes_set_targeted(record)
Expand Down Expand Up @@ -162,20 +167,24 @@ def process_scope_r208_new(karyo, genotype, record)
date = DateTime.parse(record.raw_fields['authoriseddate'])
@genes_set.concat(%w[RAD51C RAD51D]) if date >= DateTime.parse('01/02/2023')
end
elsif R208_GENE_MAPPING_TAR_NEW.include? karyo
elsif /^R240|^R242/ix.match(karyo) || /^R370.1\s::\sConfirmation\sof\sresearch\sresult/ix.match(karyo)
@logger.debug "ADDED TARGETED TEST for: #{karyo}"
genotype.add_test_scope(:targeted_mutation)
get_genes_set_targeted(record)
else
genotype.add_test_scope(:no_genetictestscope)
end
@genes_set = @genes_set.uniq
@genes_set = @genes_set.flatten.uniq
end

def process_scope_r430(karyo, genotype, _record)
if R430_GENE_MAPPING_FS.keys.include? karyo
@genes_set = R430_GENE_MAPPING_FS[karyo]
def process_scope_r430(karyo, genotype, record)
if /^R430/.match(karyo) || /^R420.1\s::\sNGS\sin\sLeeds\s-\sSend\sBlood/ix.match(karyo)
@genes_set = R430_FS_GENES
genotype.add_test_scope(:full_screen)
elsif /^R240|^R242/ix.match(karyo)
@logger.debug "ADDED TARGETED TEST for: #{karyo}"
genotype.add_test_scope(:targeted_mutation)
get_genes_set_targeted(record)
else
genotype.add_test_scope(:no_genetictestscope)
end
Expand Down Expand Up @@ -217,40 +226,46 @@ def process_scope_r242(karyo, genotype, record)
end

def add_test_type(genotype, record)
Maybe(record.raw_fields['moleculartestingtype']).each do |type|
genotype.add_molecular_testing_type_strict(TEST_TYPE_MAPPING[type.strip])
karyo = record.raw_fields['karyotypingmethod'].strip
moleculartestingtype = record.raw_fields['moleculartestingtype'].strip

test_type = determine_test_type(moleculartestingtype, karyo)
genotype.add_molecular_testing_type_strict(test_type) if test_type
end

def determine_test_type(moleculartestingtype, karyo)
# First priority: moleculartestingtype
return TEST_TYPE_MAPPING[moleculartestingtype] if TEST_TYPE_MAPPING.key?(moleculartestingtype)
return :predictive if moleculartestingtype.match?(/unaffected/i)

# Second priority: karyo R-number patterns
test_type_from_karyo(karyo)
end

def test_type_from_karyo(karyo)
case karyo
when /^R(240|205|206|207|208|209|210|211|430|444|216|414|370)/
:diagnostic
when /^R242/
:predictive
when /^R(244|246)/
:carrier
when /^R448/
:prenatal
end
end

def process_variants_from_record(genotype, record)
genotypes = []
if full_screen?(genotype)
if genotype.full_screen?
process_fullscreen_records(genotype, record, genotypes)
elsif targeted?(genotype) || no_scope?(genotype)
elsif genotype.targeted? || genotype.no_scope?
process_targeted_no_scope_records(genotype, record, genotypes)
end
genotypes
end

def full_screen?(genotype)
return if genotype.attribute_map['genetictestscope'].nil?

genotype.attribute_map['genetictestscope'].scan(/Full screen/i).size.positive?
end

def targeted?(genotype)
return if genotype.attribute_map['genetictestscope'].nil?

genotype.attribute_map['genetictestscope'].scan(/Targeted/i).size.positive?
end

def no_scope?(genotype)
return if genotype.attribute_map['genetictestscope'].nil?

genotype.attribute_map['genetictestscope'].scan(/Unable to assign/i).size.positive?
end

# rubocop:disable Metrics/MethodLength disabled as rubcop reduces redability if the method
# rubocop:disable Metrics/MethodLength -- disabled as rubocop reduces readability if the method
def process_targeted_no_scope_records(genotype, record, genotypes)
genotype_str = record.raw_fields['genotype']
positive_genes = genotype_str.scan(BRCA_REGEX).flatten.uniq
Expand Down Expand Up @@ -350,8 +365,9 @@ def add_other_genes_with_status(other_genes, genotype, genotypes, status)

def process_multi_genes(genotype, record, genotypes)
positive_genes = record.raw_fields['genotype'].scan(BRCA_REGEX).flatten
positive_genes = positive_genes.join('|')
raw_genotypes = record.raw_fields['genotype'].split(/(?=#{positive_genes})/)
positive_genes = positive_genes.uniq.join('|')
cleaned = record.raw_fields['genotype'].gsub(RISK_PREFIX_REGEX, '').strip
raw_genotypes = cleaned.split(/(?=#{positive_genes})/)

process_raw_genotypes(raw_genotypes, genotype, genotypes)
end
Expand Down
34 changes: 14 additions & 20 deletions lib/import/helpers/brca/providers/rcu/rcu_constants.rb
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Original file line number Diff line number Diff line change
Expand Up @@ -23,8 +23,10 @@ module RcuConstants
'R206 :: Inherited breast cancer ' \
'and ovarian cancer at high familial risk levels' => :process_scope_r206,
'R207 :: Inherited ovarian cancer (without breast cancer)' => :process_scope_r207,
'R207' => :process_scope_r207,
'R208 :: BRCA1 and BRCA2 testing at high familial risk' => :process_scope_r208,
'R208 :: Inherited breast cancer and ovarian cancer' => :process_scope_r208_new,
'R208' => :process_scope_r208_new,
'R240 - Familial Diagnostic testing - Hered Cancers' => :process_scope_r240,
'R242 - Predictive testing - Hered Cancers' => :process_scope_r242,
'R430 :: Inherited Prostate Cancer' => :process_scope_r430,
Expand Down Expand Up @@ -111,25 +113,12 @@ module RcuConstants
}.freeze

R207_GENE_MAPPING_FS = {
'R207.1 :: Unknown mutation(s) by Small panel' => %w[BRCA1 BRCA2 BRIP1 EPCAM MLH1
MSH2 MSH6 PALB2 RAD51C RAD51D
PMS2],
'R207.2 :: Unknown mutation(s) by MLPA or equivalent' => %w[BRCA1 BRCA2 MLH1 MSH2],
'R387.1 :: NGS analysis only' => %w[BRCA1 BRCA2 BRIP1 EPCAM MLH1 MSH2
MSH6 PALB2 RAD51C RAD51D PMS2],
'R207.1 :: NGS in Leeds' => %w[BRCA1 BRCA2 BRIP1 EPCAM MLH1 MSH2
MSH6 PALB2 RAD51C RAD51D PMS2],
'R207.1 :: NGS in Leeds - Send DNA to Leeds' => %w[BRCA1 BRCA2 BRIP1 EPCAM MLH1 MSH2
MSH6 PALB2 RAD51C RAD51D PMS2]
MSH6 PALB2 RAD51C RAD51D PMS2]
}.freeze

R207_GENE_MAPPING_TAR = [
'R240.1 :: Diagnostic familial',
'R242.1 :: Predictive testing',
'R242.1 :: Predictive testing - Seq in Leeds - Send Blood',
'R242.1 :: Predictive testing - Seq in Leeds - Send DNA',
'R242.1 :: Predictive testing - MLPA in Leeds - Send Blood'
].freeze

R207_1_FS_GENES = %w[BRCA1 BRCA2 BRIP1 EPCAM MLH1 MSH2 MSH6 PALB2 RAD51C RAD51D PMS2]

R208_GENE_MAPPING_FS = {
'R208.1 :: Unknown mutation(s) by Single gene sequencing' => %w[BRCA1 BRCA2 PALB2],
Expand Down Expand Up @@ -173,9 +162,7 @@ module RcuConstants
'R242.1 :: Predictive testing - ATM gene'
].freeze

R430_GENE_MAPPING_FS = {
'R420.1 :: NGS in Leeds - Send Blood' => %w[ATM BRCA1 BRCA2 CHEK2 MLH1 MSH2 MSH6 PALB2]
}.freeze
R430_FS_GENES = %w[ATM BRCA1 BRCA2 CHEK2 MLH1 MSH2 MSH6 PALB2].freeze

R444_GENE_MAPPING = {
'R444.1 :: PARPi for Breast cancer - NGS in Leeds' => %w[ATM BRCA1 BRCA2 CHEK2 PALB2 RAD51C RAD51D],
Expand Down Expand Up @@ -210,7 +197,14 @@ module RcuConstants

BRCA_REGEX = /(?<brca>BRCA1|BRCA2|PALB2|ATM|CHEK2|TP53|MLH1|CDH1|
MSH2|MSH6|PMS2|STK11|PTEN|BRIP1|NBN|RAD51C|RAD51D|EPCAM)/ix

GENE_PATTERN = Regexp.union(GENES_LIST)

RISK_PREFIX_REGEX = /
At\selevated\srisk\sof\s+
#{GENE_PATTERN}\s+
and\s+
#{GENE_PATTERN}-related\ cancers;
?/ix
# rubocop:disable Lint/MixedRegexpCaptureTypes
CDNA_REGEX = /((c(\.)?-?\*?(?<cdna>
(\[[0-9]+[+>_-][0-9][+>_-][0-9]+[+>_-][0-9][ACGTdelinsup]+\])|
Expand Down
133 changes: 132 additions & 1 deletion test/lib/import/brca/providers/sheffield/sheffield_handler_test.rb
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Original file line number Diff line number Diff line change
Expand Up @@ -29,9 +29,36 @@ def setup
assert_equal 'Unable to assign BRCA genetictestscope', @genotype.attribute_map['genetictestscope']
end

test 'add_test_type' do
test 'add_test_type from moleculartestingtype mapping' do
@handler.add_test_type(@genotype, @record)
assert_equal 2, @genotype.attribute_map['moleculartestingtype']
mtype_record = build_raw_record('pseudo_id1' => 'bob')
mtype_record.raw_fields['moleculartestingtype'] = 'Testing for unaffected family member'
@handler.add_test_type(@genotype, mtype_record)
assert_equal 2, @genotype.attribute_map['moleculartestingtype'] # :predictive
end

test 'add_test_type from karyo when moleculartestingtype cannot be determined' do
karyo_mtype_record = build_raw_record('pseudo_id1' => 'bob')
karyo_mtype_record.raw_fields['moleculartestingtype'] = ''
karyo_mtype_record.raw_fields['karyotypingmethod'] = 'R240.1 :: Some test'
@handler.add_test_type(@genotype, karyo_mtype_record)
assert_equal 1, @genotype.attribute_map['moleculartestingtype'] # :diagnostic
karyo_mtype_record.raw_fields['karyotypingmethod'] = 'R242.1 :: Predictive testing'
@handler.add_test_type(@genotype, karyo_mtype_record)
assert_equal 2, @genotype.attribute_map['moleculartestingtype'] # :predictive
karyo_mtype_record.raw_fields['karyotypingmethod'] = 'R448.1 :: Prenatal testing'
@handler.add_test_type(@genotype, karyo_mtype_record)
assert_equal 4, @genotype.attribute_map['moleculartestingtype'] # :prenatal
end

test 'add_test_type moleculartestingtype takes priority over karyo' do
priority_record = build_raw_record('pseudo_id1' => 'bob')
priority_record.raw_fields['moleculartestingtype'] = 'Diagnostic testing'
priority_record.raw_fields['karyotypingmethod'] = 'R242.1 :: Predictive testing'
@handler.add_test_type(@genotype, priority_record)
# Should be diagnostic from moleculartestingtype, not predictive from karyo
assert_equal 1, @genotype.attribute_map['moleculartestingtype']
end

test 'process_variants_from_record' do
Expand Down Expand Up @@ -311,6 +338,110 @@ def setup
assert_nil genotypes[1].attribute_map['codingdnasequencechange']
end

test 'process_scope_r207 with R207.1 full screen' do
r207_1_record = build_raw_record('pseudo_id1' => 'bob')
r207_1_record.raw_fields['genetictestscope'] = 'R207 :: Inherited ovarian cancer (without breast cancer)'
r207_1_record.raw_fields['karyotypingmethod'] = 'R207.1 :: NGS in Leeds'
r207_1_record.raw_fields['genotype'] = 'BRCA1-c.5266dup-p.(Gln1756fs)-Heterozygous-UV5;MSH6-c.3649A>G-p.(Arg1217Gly)-Heterozygous-UV3'
@handler.add_test_scope_from_geno_karyo(@genotype, r207_1_record)
assert_equal 'Full screen BRCA1 and BRCA2', @genotype.attribute_map['genetictestscope']
genotypes = @handler.process_variants_from_record(@genotype, r207_1_record)
assert_equal 11, genotypes.size
variant_genotype_brca = genotypes.find { |g| g.attribute_map['gene'] == 7 } # BRCA1
assert_equal 2, variant_genotype_brca.attribute_map['teststatus']
assert_equal 'c.5266dup', variant_genotype_brca.attribute_map['codingdnasequencechange']
assert_equal 'p.Gln1756fs', variant_genotype_brca.attribute_map['proteinimpact']

variant_genotype_msh6 = genotypes.find { |g| g.attribute_map['gene'] == 2808 } # MSH6
assert_equal 2, variant_genotype_msh6.attribute_map['teststatus']
assert_equal 'c.3649A>G', variant_genotype_msh6.attribute_map['codingdnasequencechange']
assert_equal 'p.Arg1217Gly', variant_genotype_msh6.attribute_map['proteinimpact']
genotypes.each do |genotype|
next if [7, 2808].include?(genotype.attribute_map['gene'])

assert_equal 1, genotype.attribute_map['teststatus']
end
end

test 'process_scope_r207 with R240 targeted' do
r207_r240_record = build_raw_record('pseudo_id1' => 'bob')
r207_r240_record.raw_fields['genetictestscope'] = 'R207'
r207_r240_record.raw_fields['karyotypingmethod'] = 'R240 :: Diagnostic testing for known pathogenic variant(s) - Hereditary Cancers'
r207_r240_record.raw_fields['genotype'] = 'Genetic diagnosis of BRCA2-related cancer susceptibility; BRCA2(NM_000059.3);c.4218_4221del;p.(Lys1406Asnfs*3);Heterozygous;UV5'
@handler.add_test_scope_from_geno_karyo(@genotype, r207_r240_record)
assert_equal 'Targeted BRCA mutation test', @genotype.attribute_map['genetictestscope']
genotypes = @handler.process_variants_from_record(@genotype, r207_r240_record)
assert_equal 1, genotypes.size
assert_equal 2, genotypes[0].attribute_map['teststatus']
assert_equal 8, genotypes[0].attribute_map['gene']
assert_equal 'c.4218_4221del', genotypes[0].attribute_map['codingdnasequencechange']
assert_equal 'p.Lys1406AsnfsTer3', genotypes[0].attribute_map['proteinimpact']
end

test 'process_scope_r208_new with R242 targeted' do
r208_r242_record = build_raw_record('pseudo_id1' => 'bob')
r208_r242_record.raw_fields['genetictestscope'] = 'R208'
r208_r242_record.raw_fields['karyotypingmethod'] = 'R242 :: Predictive testing for known familial pathogenic variant(s) - Hereditary Cancers'
r208_r242_record.raw_fields['genotype'] = 'At elevated risk of BRCA1 and BRCA2-related cancers; BRCA1(NM_007294.3);deletion including exons 1-2Heterozygous;'
@handler.add_test_scope_from_geno_karyo(@genotype, r208_r242_record)
assert_equal 'Targeted BRCA mutation test', @genotype.attribute_map['genetictestscope']
genotypes = @handler.process_variants_from_record(@genotype, r208_r242_record)
assert_equal 1, genotypes.size
assert_equal 2, genotypes[0].attribute_map['teststatus']
assert_equal 7, genotypes[0].attribute_map['gene']
end

test 'process_scope_r430 with R430 full screen' do
r430_record = build_raw_record('pseudo_id1' => 'bob')
r430_record.raw_fields['genetictestscope'] = 'R430 :: Inherited Prostate Cancer'
r430_record.raw_fields['karyotypingmethod'] = 'R430.1 :: NGS in Leeds'
r430_record.raw_fields['genotype'] = 'Genetic diagnosis of CHEK2-related cancer susceptibility; CHEK2(NM_007194.4);c.1100del;p.(Glu1493fs);Heterozygous;UV5'
@handler.add_test_scope_from_geno_karyo(@genotype, r430_record)
assert_equal 'Full screen BRCA1 and BRCA2', @genotype.attribute_map['genetictestscope']
genotypes = @handler.process_variants_from_record(@genotype, r430_record)
assert_equal 8, genotypes.size
variant_genotype = genotypes.find { |g| g.attribute_map['gene'] == 865 } # CHEK2
assert_equal 2, variant_genotype.attribute_map['teststatus']
assert_equal 'c.1100del', variant_genotype.attribute_map['codingdnasequencechange']
assert_equal 'p.Glu1493fs', variant_genotype.attribute_map['proteinimpact']

genotypes.each do |genotype|
next if genotype.attribute_map['gene'] == 865

assert_equal 1, genotype.attribute_map['teststatus']
end
end

test 'process_scope_r207 with R387.1 targeted' do
r207_r387_1_record = build_raw_record('pseudo_id1' => 'bob')
r207_r387_1_record.raw_fields['genetictestscope'] = 'R207'
r207_r387_1_record.raw_fields['karyotypingmethod'] = 'R387.1 :: Reanalysis of existing NGS data'
r207_r387_1_record.raw_fields['genotype'] = 'No variant detected'
@handler.add_test_scope_from_geno_karyo(@genotype, r207_r387_1_record)
assert_equal 'Full screen BRCA1 and BRCA2', @genotype.attribute_map['genetictestscope']
genotypes = @handler.process_variants_from_record(@genotype, r207_r387_1_record)
assert_equal 11, genotypes.size
genotypes.each do |genotype|
assert_not_nil genotype.attribute_map['gene']
assert_equal 1, genotype.attribute_map['teststatus']
end
end

test 'process_scope_r208 with R370.1 targeted' do
r208_r370_1_record = build_raw_record('pseudo_id1' => 'bob')
r208_r370_1_record.raw_fields['genetictestscope'] = 'R208 :: Inherited breast cancer and ovarian cancer'
r208_r370_1_record.raw_fields['karyotypingmethod'] = 'R370.1 :: Confirmation of research result'
r208_r370_1_record.raw_fields['genotype'] = 'BRCA1-GRCh38(chr17):g.43118884_43155545dup; (NM_007294.3):c.1100del-Heterozygous-UV3'
@handler.add_test_scope_from_geno_karyo(@genotype, r208_r370_1_record)
assert_equal 'Targeted BRCA mutation test', @genotype.attribute_map['genetictestscope']
genotypes = @handler.process_variants_from_record(@genotype, r208_r370_1_record)
assert_equal 1, genotypes.size
assert_equal 2, genotypes[0].attribute_map['teststatus']
assert_equal 7, genotypes[0].attribute_map['gene']
assert_equal 'c.1100del', genotypes[0].attribute_map['codingdnasequencechange']
assert_nil genotypes[0].attribute_map['proteinimpact']
end

private

def clinical_json
Expand Down
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