Reformat sample_questions.json

sample_questions.json

@@ -6,19 +6,24 @@
         {
           "gene": "DMD",
           "transcript": "NM_004006.2",
-          "variant_hgvs": "c.7544_9286del",
-          "protein_hgvs": "p.(Thr2516_Ala3096del)",
+          "variant_cdna": "c.7544_9286del",
+          "variant_protein": "p.(Thr2516_Ala3096del)",
           "zygosity": "hemizygous"
         }
       ],
       "clinical_context": "Progressive muscle weakness"
     },
-    "question": "To which of the following targeted therapies would this variant be most likely amenable: Golodirsen, Viltolarsen, Eteplirsen, Casimersen, Ataluren, or None?",
-    "answer": "Eteplirsen",
-    "answer_type": "multipleChoice",
-    "category": "Established_Targeted",
-    "sub_category": "ASO",
-    "rationale": "Variant results in deletion of exons 52-63, which is listed as amenable to exon 51 skipping"
+    "question": {
+      "category": "Established_Targeted",
+      "answer_format": "multiple_choice",
+      "prompt": "To which of the following targeted therapies would this variant be most likely amenable: Golodirsen, Viltolarsen, Eteplirsen, Casimersen, Ataluren, or None?",
+      "date_submitted": "2025-08-01"
+    },
+    "answer_expected": "Eteplirsen",
+    "answer_explanation": "Variant results in deletion of exons 52-63, which is listed as amenable to exon 51 skipping",
+    "difficulty_rationale": "",
+    "sources": ["GeneReviews", "PubMed/Literature"],
+    "citations": []
   },
   {
     "id": "AITX-00002",
@@ -27,19 +32,24 @@
         {
           "gene": "DMD",
           "transcript": "NM_004006.2",
-          "variant_hgvs": "c.10453_10454delinsTA",
-          "protein_hgvs": "p.(Leu3485Ter)",
+          "variant_cdna": "c.10453_10454delinsTA",
+          "variant_protein": "p.(Leu3485Ter)",
           "zygosity": "hemizygous"
         }
       ],
       "clinical_context": "Progressive muscle weakness"
     },
-    "question": "To which of the following targeted therapies would this variant be most likely amenable: Golodirsen, Viltolarsen, Eteplirsen, Casimersen, Ataluren, or None?",
-    "answer": "Ataluren",
-    "answer_type": "multipleChoice",
-    "category": "Established_Targeted",
-    "sub_category": "Small Molecule",
-    "rationale": "Variant results in a nonsense in exon 74, which is amenable to nonsense readthrough"
+    "question": {
+      "category": "Established_Targeted",
+      "answer_format": "multiple_choice",
+      "prompt": "To which of the following targeted therapies would this variant be most likely amenable: Golodirsen, Viltolarsen, Eteplirsen, Casimersen, Ataluren, or None?",
+      "date_submitted": "2025-08-01"
+    },
+    "answer_expected": "Ataluren",
+    "answer_explanation": "Variant results in a nonsense in exon 74, which is amenable to nonsense readthrough",
+    "difficulty_rationale": "",
+    "sources": [],
+    "citations": []
   },
   {
     "id": "AITX-00003",
@@ -48,19 +58,24 @@
         {
           "gene": "DMD",
           "transcript": "NM_004006.2",
-          "variant_hgvs": "c.70T>C",
-          "protein_hgvs": "p.(Trp24Arg)",
+          "variant_cdna": "c.70T>C",
+          "variant_protein": "p.(Trp24Arg)",
           "zygosity": "hemizygous"
         }
       ],
       "clinical_context": "Progressive muscle weakness"
     },
-    "question": "To which of the following targeted therapies would this variant be most likely amenable: Eteplirsen, Golodirsen, Viltolarsen, Casimersen, Ataluren, or None?",
-    "answer": "None",
-    "answer_type": "multipleChoice",
-    "category": "Established_Targeted",
-    "sub_category": "ASOs",
-    "rationale": "Results in a missense in exon 2, which is not amenable to nonsense readthrough and is upstream from skippable exons"
+    "question": {
+      "category": "Established_Targeted",
+      "answer_format": "multiple_choice",
+      "prompt": "To which of the following targeted therapies would this variant be most likely amenable: Eteplirsen, Golodirsen, Viltolarsen, Casimersen, Ataluren, or None?",
+      "date_submitted": "2025-08-01"
+    },
+    "answer_expected": "None",
+    "answer_explanation": "Results in a missense in exon 2, which is not amenable to nonsense readthrough and is upstream from skippable exons",
+    "difficulty_rationale": "",
+    "sources": [],
+    "citations": []
   },
   {
     "id": "AITX-00004",
@@ -69,19 +84,24 @@
         {
           "gene": "AGXT",
           "transcript": "NM_000030.3",
-          "variant_hgvs": "c.508G>A",
-          "protein_hgvs": "p.(Gly170Arg)",
+          "variant_cdna": "c.508G>A",
+          "variant_protein": "p.(Gly170Arg)",
           "zygosity": "homozygous"
         }
       ],
       "clinical_context": "Recurrent nephrocalcinosis and chronic kidney disease"
     },
-    "question": "What targeted, small molecule therapy is available for this patient? Provide the generic name or None.",
-    "answer": "Pyridoxine",
-    "answer_type": "exactMatch",
-    "category": "Established_Targeted",
-    "sub_category": "Small Molecule",
-    "rationale": "Missense variants are amenable to pyridoxine treatment https://www.ncbi.nlm.nih.gov/books/NBK1283/"
+    "question": {
+      "category": "Established_Targeted",
+      "answer_format": "string_match",
+      "prompt": "What targeted, small molecule therapy is available for this patient? Provide the generic name or None.",
+      "date_submitted": "2025-08-01"
+    },
+    "answer_expected": "Pyridoxine",
+    "answer_explanation": "Missense variants are amenable to pyridoxine treatment",
+    "difficulty_rationale": "",
+    "sources": ["GeneReviews"],
+    "citations": ["https://www.ncbi.nlm.nih.gov/books/NBK1283/"]
   },
   {
     "id": "AITX-00005",
@@ -90,19 +110,24 @@
         {
           "gene": "AGXT",
           "transcript": "NM_000030.3",
-          "variant_hgvs": "c.33dup",
-          "protein_hgvs": "p.(Lys12GlnfsTer156)",
+          "variant_cdna": "c.33dup",
+          "variant_protein": "p.(Lys12GlnfsTer156)",
           "zygosity": "homozygous"
         }
       ],
       "clinical_context": "Recurrent nephrocalcinosis and chronic kidney disease"
     },
-    "question": "Is this patient predicted to be responsive to pyridoxine? Answer yes or no.",
-    "answer": "No",
-    "answer_type": "exactMatch",
-    "category": "Established_Targeted",
-    "sub_category": "Small Molecule",
-    "rationale": "Pyridoxine is not effective for patients with null variants https://www.ncbi.nlm.nih.gov/books/NBK1283/"
+    "question": {
+      "category": "Established_Targeted",
+      "answer_format": "binary",
+      "prompt": "Is this patient predicted to be responsive to pyridoxine? Answer yes or no.",
+      "date_submitted": "2025-08-01"
+    },
+    "answer_expected": "No",
+    "answer_explanation": "Pyridoxine is not effective for patients with null variants",
+    "difficulty_rationale": "",
+    "sources": ["GeneReviews"],
+    "citations": ["https://www.ncbi.nlm.nih.gov/books/NBK1283/"]
   },
   {
     "id": "AITX-00006",
@@ -111,19 +136,24 @@
         {
           "gene": "AGXT",
           "transcript": "NM_000030.3",
-          "variant_hgvs": "c.33dup",
-          "protein_hgvs": "p.(Lys12GlnfsTer156)",
+          "variant_cdna": "c.33dup",
+          "variant_protein": "p.(Lys12GlnfsTer156)",
           "zygosity": "homozygous"
         }
       ],
       "clinical_context": "7 year old with recurrent nephrocalcinosis and chronic kidney disease"
     },
-    "question": "What targeted, genetic therapies are approved for this patient in the US? Provide the generic name.",
-    "answer": "Lumasiran",
-    "answer_type": "exactMatch",
-    "category": "Established_Targeted",
-    "sub_category": "siRNA",
-    "rationale": "Lumasiran is approved for patients of all ages whereas Nedosiran is only approved for patients age >9. https://www.ncbi.nlm.nih.gov/books/NBK1283/"
+    "question": {
+      "category": "Established_Targeted",
+      "answer_format": "string_match",
+      "prompt": "What targeted, genetic therapies are approved for this patient in the US? Provide the generic name.",
+      "date_submitted": "2025-08-01"
+    },
+    "answer_expected": "Lumasiran",
+    "answer_explanation": "Lumasiran is approved for patients of all ages whereas Nedosiran is only approved for patients age >9.",
+    "difficulty_rationale": "slight change in patient age changes the answer",
+    "sources": ["GeneReviews"],
+    "citations": ["https://www.ncbi.nlm.nih.gov/books/NBK1283/"]
   },
   {
     "id": "AITX-00007",
@@ -132,19 +162,24 @@
         {
           "gene": "DDC",
           "transcript": "NM_001082971.2",
-          "variant_hgvs": "c.286G>A",
-          "protein_hgvs": "p.(Gly96Arg)",
+          "variant_cdna": "c.286G>A",
+          "variant_protein": "p.(Gly96Arg)",
           "zygosity": "homozygous"
         }
       ],
       "clinical_context": "Global developmental delay"
     },
-    "question": "What is the youngest age for which a gene therapy is approved for this patient's genetic condition in the united kingdom? Answer with the format \"X months\".",
-    "answer": "18 months",
-    "answer_type": "exactMatch",
-    "category": "Established_Targeted",
-    "sub_category": "Gene Therapy",
-    "rationale": "https://www.ncbi.nlm.nih.gov/books/NBK595821/"
+    "question": {
+      "category": "Established_Targeted",
+      "answer_format": "string_match",
+      "prompt": "What is the youngest age for which a gene therapy is approved for this patient's genetic condition in the united kingdom? Answer with the format \"X months\".",
+      "date_submitted": "2025-08-01"
+    },
+    "answer_expected": "18 months",
+    "answer_explanation": "specified on GeneReviews",
+    "difficulty_rationale": "",
+    "sources": ["GeneReviews"],
+    "citations": ["https://www.ncbi.nlm.nih.gov/books/NBK595821/"]
   },
   {
     "id": "AITX-00008",
@@ -153,19 +188,24 @@
         {
           "gene": "COL1A1",
           "transcript": "NM_000088.4",
-          "variant_hgvs": "c.1678G>A",
-          "protein_hgvs": "p.(Gly560Ser)",
+          "variant_cdna": "c.1678G>A",
+          "variant_protein": "p.(Gly560Ser)",
           "zygosity": "heterozygous"
         }
       ],
       "clinical_context": "joint hypermobility, skin hyperextensibility, and easy bruising"
     },
-    "question": "What two medications are most established for decreasing bruising? List generic names in alphabetical order",
-    "answer": "ascorbic acid, desmopressin",
-    "answer_type": "exactMatch",
-    "category": "Established_Supportive",
-    "sub_category": "Treatment_Identification",
-    "rationale": "https://www.ncbi.nlm.nih.gov/books/NBK1244/#eds.Management"
+    "question": {
+      "category": "Established_Supportive",
+      "answer_format": "string_match",
+      "prompt": "What two medications are most established for decreasing bruising? List generic names in alphabetical order",
+      "date_submitted": "2025-08-01"
+    },
+    "answer_expected": "ascorbic acid, desmopressin",
+    "answer_explanation": "specified in management on GeneReviews",
+    "difficulty_rationale": "",
+    "sources": ["GeneReviews"],
+    "citations": ["https://www.ncbi.nlm.nih.gov/books/NBK1244/#eds.Management"]
   },
   {
     "id": "AITX-00009",
@@ -174,19 +214,24 @@
         {
           "gene": "SLC35A2",
           "transcript": "NM_005660.3",
-          "variant_hgvs": "c.3G>A",
-          "protein_hgvs": "p.Met1Ile",
+          "variant_cdna": "c.3G>A",
+          "variant_protein": "p.Met1Ile",
           "zygosity": "heterozygous"
         }
       ],
       "clinical_context": "Patient with SLC35A2-CDG who is experiencing seizures and global developmental delay"
     },
-    "question": "What clinical trial developing a new therapeutic for this condition is recruiting or listed as upcoming/not yet recruiting? Return a clinical trials ID",
-    "answer": "NCT05402384",
-    "answer_type": "exactMatch",
-    "category": "Clinical_Trials",
-    "sub_category": "Trial_Identification",
-    "rationale": "https://clinicaltrials.gov/study/NCT05402384"
+    "question": {
+      "category": "Clinical_Trials",
+      "answer_format": "string_match",
+      "prompt": "What clinical trial developing a new therapeutic for this condition is recruiting or listed as upcoming/not yet recruiting? Return a clinical trials ID",
+      "date_submitted": "2025-08-01"
+    },
+    "answer_expected": "NCT05402384",
+    "answer_explanation": "search for SLC35A2 on ClinicalTrials.gov returns only 2 trials, 1 of which is upcoming",
+    "difficulty_rationale": "",
+    "sources": ["ClinicalTrials.gov"],
+    "citations": ["https://clinicaltrials.gov/study/NCT05402384"]
   },
   {
     "id": "AITX-00010",
@@ -195,19 +240,24 @@
         {
           "gene": "SLC35A2",
           "transcript": "NM_005660.3",
-          "variant_hgvs": "c.3G>A",
-          "protein_hgvs": "p.Met1Ile",
+          "variant_cdna": "c.3G>A",
+          "variant_protein": "p.Met1Ile",
           "zygosity": "heterozygous"
         }
       ],
       "clinical_context": "seizures and global developmental delay. Age 2 months, Hemoglobin 5, Normal liver labs, Not enrolled in other trials"
     },
-    "question": "Is this patient eligible for clinical trial NCT05402384? Answer yes or no.",
-    "answer": "No",
-    "answer_type": "exactMatch",
-    "category": "Clinical_Trials",
-    "sub_category": "Eligibility",
-    "rationale": "Exclusion criteria lists hemoglobin <7 https://clinicaltrials.gov/study/NCT05402384"
+    "question": {
+      "category": "Clinical_Trials",
+      "answer_format": "binary",
+      "prompt": "Is this patient eligible for clinical trial NCT05402384? Answer yes or no.",
+      "date_submitted": "2025-08-01"
+    },
+    "answer_expected": "No",
+    "answer_explanation": "Exclusion criteria lists hemoglobin <7",
+    "difficulty_rationale": "",
+    "sources": ["ClinicalTrials.gov"],
+    "citations": ["https://clinicaltrials.gov/study/NCT05402384"]
   },
   {
     "id": "AITX-00011",
@@ -216,19 +266,24 @@
         {
           "gene": "KCNT1",
           "transcript": "NM_020822.3",
-          "variant_hgvs": "c.2849G>A",
-          "protein_hgvs": "p.Arg950Gln",
+          "variant_cdna": "c.2849G>A",
+          "variant_protein": "p.Arg950Gln",
           "zygosity": "heterozygous"
         }
       ],
       "clinical_context": "early-onset seizures and developmental delays"
     },
-    "question": "For which clinical trials evaluating new therapeutics is this patient eligible? Provide a clinical trial ID or answer None.",
-    "answer": "None",
-    "answer_type": "exactMatch",
-    "category": "Clinical_Trials",
-    "sub_category": "Trial_Identification",
-    "rationale": "Only a natural history study is listed. Source: https://clinicaltrials.gov/search?cond=KCNT1"
+    "question": {
+      "category": "Clinical_Trials",
+      "answer_format": "string_match",
+      "prompt": "For which clinical trials evaluating new therapeutics is this patient eligible? Provide a clinical trial ID or answer None.",
+      "date_submitted": "2025-08-01"
+    },
+    "answer_expected": "None",
+    "answer_explanation": "Only a natural history study is listed.",
+    "difficulty_rationale": "",
+    "sources": ["ClinicalTrials.gov"],
+    "citations": ["https://clinicaltrials.gov/search?cond=KCNT1"]
   },
   {
     "id": "AITX-00012",
@@ -237,19 +292,24 @@
         {
           "gene": "GRIN2B",
           "transcript": "NM_000834.5",
-          "variant_hgvs": "c.2755C>T",
-          "protein_hgvs": "p.Gln919Ter",
+          "variant_cdna": "c.2755C>T",
+          "variant_protein": "p.Gln919Ter",
           "zygosity": "heterozygous"
         }
       ],
       "clinical_context": "intellectual disability, seizures, and developmental delays"
     },
-    "question": "Is it more likely amenable to treatment with Memantine, L-serine, or Radiprodil",
-    "answer": "L-Serine",
-    "answer_type": "exactMatch",
-    "category": "Drug_Development_and_Repurposing",
-    "sub_category": "Mechanism_Of_Action",
-    "rationale": "Variant is a LOF variant. L-serine is being used for LOF variants whereas the others are being used for GOF variants https://academic.oup.com/brain/article/147/5/1653/7611854?login=false"
+    "question": {
+      "category": "Drug_Development_and_Repurposing",
+      "answer_format": "multiple_choice",
+      "prompt": "Is it more likely amenable to treatment with Memantine, L-serine, or Radiprodil",
+      "date_submitted": "2025-08-01"
+    },
+    "answer_expected": "L-Serine",
+    "answer_explanation": "Variant is a LOF variant. L-serine is being used for LOF variants whereas the others are being used for GOF variants",
+    "difficulty_rationale": "",
+    "sources": ["PubMed/Literature"],
+    "citations": ["https://academic.oup.com/brain/article/147/5/1653/7611854?login=false"]
   },
   {
     "id": "AITX-00013",
@@ -258,19 +318,25 @@
         {
           "gene": "ANO10",
           "transcript": "NM_018075.5",
-          "variant_hgvs": "c.289del",
-          "protein_hgvs": "p.(Met97Ter)",
+          "variant_cdna": "c.289del",
+          "variant_protein": "p.(Met97Ter)",
           "zygosity": "homozygous"
         }
       ],
       "clinical_context": "progressive cerebellar ataxia and peripheral neuropathy"
     },
-    "question": "How many amino acids are coded for by the exon in which this variant occurs? Answer with a number",
-    "answer": "66",
-    "answer_type": "exactMatch",
-    "category": "Variant_Assessment",
-    "sub_category": "Exon_Evaluation",
-    "rationale": "Source: Ensembl"
+    "question": {
+      "category": "Variant_Assessment",
+      "answer_format": "numeric_match",
+      "prompt": "How many amino acids are coded for by the exon in which this variant occurs? Answer with a number",
+      "date_submitted": "2025-08-01"
+    },
+    "answer_expected": "66",
+    "answer_explanation": "visual inspection on Ensembl",
+    "difficulty_rationale": "",
+    "sources": ["Other"],
+    "otherSource": "Ensembl",
+    "citations": []
   },
   {
     "id": "AITX-00014",
@@ -279,19 +345,25 @@
         {
           "gene": "ANO10",
           "transcript": "NM_018075.5",
-          "variant_hgvs": "c.289del",
-          "protein_hgvs": "p.(Met97Ter)",
+          "variant_cdna": "c.289del",
+          "variant_protein": "p.(Met97Ter)",
           "zygosity": "homozygous"
         }
       ],
       "clinical_context": "progressive cerebellar ataxia and peripheral neuropathy"
     },
-    "question": "What percentage of the total coding transcript for this gene are encoded by the exon in which this variant occurs? Answer with a decimal to nearest tenth.",
-    "answer": "0.1",
-    "answer_type": "exactMatch",
-    "category": "Variant_Assessment",
-    "sub_category": "Exon_Evaluation",
-    "rationale": "66/660 = 0.1 Source: Ensembl"
+    "question": {
+      "category": "Variant_Assessment",
+      "answer_format": "numeric_match",
+      "prompt": "What percentage of the total coding transcript for this gene are encoded by the exon in which this variant occurs? Answer with a decimal to nearest tenth.",
+      "date_submitted": "2025-08-01"
+    },
+    "answer_expected": "0.1",
+    "answer_explanation": "66/660 = 0.1",
+    "difficulty_rationale": "",
+    "sources": ["Other"],
+    "otherSource": "Ensembl",
+    "citations": []
   },
   {
     "id": "AITX-00015",
@@ -300,19 +372,25 @@
         {
           "gene": "KMT2B",
           "transcript": "NM_014727.3",
-          "variant_hgvs": "c.8079delC",
-          "protein_hgvs": "p.(Ile2694SerfsTer44)",
+          "variant_cdna": "c.8079delC",
+          "variant_protein": "p.(Ile2694SerfsTer44)",
           "zygosity": "heterozygous"
         }
       ],
       "clinical_context": "childhood-onset generalized dystonia"
     },
-    "question": "Based on typical prediction rules, is this variant likely to result in nonsense mediated decay? Answer yes or no.",
-    "answer": "No",
-    "answer_type": "exactMatch",
-    "category": "Variant_Assessment",
-    "sub_category": "Nonsense_Mediated_Decay",
-    "rationale": "At the end of the last exon, after the main domain"
+    "question": {
+      "category": "Variant_Assessment",
+      "answer_format": "binary",
+      "prompt": "Based on typical prediction rules, is this variant likely to result in nonsense mediated decay? Answer yes or no.",
+      "date_submitted": "2025-08-01"
+    },
+    "answer_expected": "No",
+    "answer_explanation": "At the end of the last exon, after the main domain",
+    "difficulty_rationale": "",
+    "sources": ["Other"],
+    "otherSource": "Ensembl",
+    "citations": []
   },
   {
     "id": "AITX-00016",
@@ -321,18 +399,23 @@
         {
           "gene": "NF1",
           "transcript": "NM_001042492.3",
-          "variant_hgvs": "c.3728T>C",
-          "protein_hgvs": "p.(Leu1243Pro)",
+          "variant_cdna": "c.3728T>C",
+          "variant_protein": "p.(Leu1243Pro)",
           "zygosity": "heterozygous"
         }
       ],
       "clinical_context": "Malignant Peripheral Nerve Sheath Tumor and Pheochromocytoma"
     },
-    "question": "In which functional domain does this variant occur? Answer choices: CSRD, TBD, GRD, Sec14-PH, HLR, NLS, SBR.",
-    "answer": "GRD",
-    "answer_type": "exactMatch",
-    "category": "Variant_Assessment",
-    "sub_category": "Exon_Skipping",
-    "rationale": "GRD, GAP related domain (1198–1549 residues) https://www.mdpi.com/2073-4425/13/7/1130#"
+    "question": {
+      "category": "Variant_Assessment",
+      "answer_format": "multiple_choice",
+      "prompt": "In which functional domain does this variant occur? Answer choices: CSRD, TBD, GRD, Sec14-PH, HLR, NLS, SBR.",
+      "date_submitted": "2025-08-01"
+    },
+    "answer_expected": "GRD",
+    "answer_explanation": "GRD, GAP related domain (1198–1549 residues)",
+    "difficulty_rationale": "",
+    "sources": ["PubMed/Literature"],
+    "citations": ["https://www.mdpi.com/2073-4425/13/7/1130#"]
   }
 ]