{
  "version": "20260604_core_validation_v45",
  "scope_note": "Off-target classes are mechanism-oriented evidence buckets for browsing and benchmark reuse; they are not de novo off-target predictions for a submitted sequence.",
  "release_records": 111,
  "benchmark_records": 81,
  "candidate_records": 28649,
  "classes": [
    {
      "key": "seed_mediated",
      "label": "Seed-mediated / miRNA-like",
      "definition": "Evidence mentions seed region, 3'UTR seed matching, miRNA-like repression, or seed-driven transcriptome effects.",
      "synonyms": [
        "seed",
        "3'utr",
        "3 utr",
        "mirna",
        "microrna",
        "seed-mediated",
        "seed match"
      ],
      "release_records": 47,
      "benchmark_records": 32,
      "candidate_records": 1259,
      "grade_counts": [
        {
          "grade": "A",
          "n": 12
        },
        {
          "grade": "B",
          "n": 24
        },
        {
          "grade": "C",
          "n": 11
        }
      ],
      "examples": [
        {
          "record": "offtarget_evidence:1",
          "canonical_name": "SNA-modified GalNAc-siRNA panel from PMID 41994868",
          "evidence_label": "seed-mediated off-target effect",
          "evidence_grade": "A",
          "pmid": "41994868"
        },
        {
          "record": "offtarget_evidence:2",
          "canonical_name": "siVIM-270 chemical modification panel from PMID 41467115",
          "evidence_label": "seed-mediated off-target effect",
          "evidence_grade": "A",
          "pmid": "41467115"
        },
        {
          "record": "offtarget_evidence:7",
          "canonical_name": "ALN-HBV/ALN-HBV02 GalNAc-siRNA panel from PMID 35736224",
          "evidence_label": "seed-mediated off-target effect",
          "evidence_grade": "A",
          "pmid": "35736224"
        },
        {
          "record": "offtarget_evidence:8",
          "canonical_name": "GalNAc-siRNA panel from PMID 29459660",
          "evidence_label": "seed-mediated off-target effect",
          "evidence_grade": "A",
          "pmid": "29459660"
        }
      ],
      "endpoint": "/api/evidence_records?domain=offtarget&q=seed"
    },
    {
      "key": "hybridization_mismatch",
      "label": "Hybridization or mismatch",
      "definition": "Evidence concerns partial complementarity, mismatch tolerance, hybridization-driven off-targeting, or unintended RNA binding.",
      "synonyms": [
        "hybridization",
        "mismatch",
        "partial complementarity",
        "complementarity",
        "unintended binding"
      ],
      "release_records": 30,
      "benchmark_records": 27,
      "candidate_records": 1586,
      "grade_counts": [
        {
          "grade": "A",
          "n": 10
        },
        {
          "grade": "B",
          "n": 19
        },
        {
          "grade": "C",
          "n": 1
        }
      ],
      "examples": [
        {
          "record": "offtarget_evidence:4",
          "canonical_name": "APP-AON/ATXN3-AON/HTT-AON panel from PMID 41066632",
          "evidence_label": "hybridization/mismatch off-target effect",
          "evidence_grade": "A",
          "pmid": "41066632"
        },
        {
          "record": "offtarget_evidence:5",
          "canonical_name": "PNA-braced ASO panel from PMID 38042877",
          "evidence_label": "hybridization/mismatch off-target effect",
          "evidence_grade": "A",
          "pmid": "38042877"
        },
        {
          "record": "offtarget_evidence:10",
          "canonical_name": "GSK2910546A ASO gapmer panel from PMID 26338776",
          "evidence_label": "hybridization/mismatch off-target effect",
          "evidence_grade": "A",
          "pmid": "26338776"
        },
        {
          "record": "offtarget_evidence:13",
          "canonical_name": "ASO candidate from PMID 36229039",
          "evidence_label": "hybridization/mismatch off-target effect",
          "evidence_grade": "B",
          "pmid": "36229039"
        }
      ],
      "endpoint": "/api/evidence_records?domain=offtarget&q=hybridization"
    },
    {
      "key": "transcriptome_level",
      "label": "Transcriptome-level observation",
      "definition": "Evidence is supported by expression profiling, RNA-seq, microarray, transcriptome-wide readout, or gene-expression signatures.",
      "synonyms": [
        "rna-seq",
        "rnaseq",
        "transcriptome",
        "microarray",
        "expression profiling",
        "gene expression"
      ],
      "release_records": 19,
      "benchmark_records": 13,
      "candidate_records": 3064,
      "grade_counts": [
        {
          "grade": "A",
          "n": 9
        },
        {
          "grade": "B",
          "n": 10
        }
      ],
      "examples": [
        {
          "record": "offtarget_evidence:6",
          "canonical_name": "DM1 ASO panel from PMID 37200862",
          "evidence_label": "transcriptome-level off-target effect",
          "evidence_grade": "A",
          "pmid": "37200862"
        },
        {
          "record": "offtarget_evidence:36",
          "canonical_name": "CCND1; Drisapersen; Mipomersen",
          "evidence_label": "transcriptome-level off-target effect",
          "evidence_grade": "B",
          "pmid": "35464859"
        },
        {
          "record": "offtarget_evidence:44",
          "canonical_name": "unspecified antisense oligonucleotide",
          "evidence_label": "transcriptome-level off-target effect",
          "evidence_grade": "B",
          "pmid": "37310350"
        },
        {
          "record": "offtarget_evidence:47",
          "canonical_name": "unspecified antisense oligonucleotide",
          "evidence_label": "transcriptome-level off-target effect",
          "evidence_grade": "B",
          "pmid": "33314011"
        }
      ],
      "endpoint": "/api/evidence_records?domain=offtarget&q=rna-seq"
    },
    {
      "key": "general_offtarget",
      "label": "General off-target",
      "definition": "Curated off-target evidence where the source does not cleanly specify one of the higher-resolution mechanisms.",
      "synonyms": [
        "off-target",
        "off target",
        "offtarget",
        "unintended"
      ],
      "release_records": 12,
      "benchmark_records": 8,
      "candidate_records": 21945,
      "grade_counts": [
        {
          "grade": "A",
          "n": 2
        },
        {
          "grade": "B",
          "n": 10
        }
      ],
      "examples": [
        {
          "record": "offtarget_evidence:3",
          "canonical_name": "RGLS4326",
          "evidence_label": "off-target evidence",
          "evidence_grade": "B",
          "pmid": "41315228"
        },
        {
          "record": "offtarget_evidence:15",
          "canonical_name": "siRNA candidate from PMID 29246303",
          "evidence_label": "off-target evidence",
          "evidence_grade": "B",
          "pmid": "29246303"
        },
        {
          "record": "offtarget_evidence:16",
          "canonical_name": "siRNA candidate from PMID 41897327",
          "evidence_label": "sequence-specificity/off-target evidence",
          "evidence_grade": "B",
          "pmid": "41897327"
        },
        {
          "record": "offtarget_evidence:40",
          "canonical_name": "SPC2996; PC3; CaCo2",
          "evidence_label": "off-target evidence",
          "evidence_grade": "A",
          "pmid": "19854938"
        }
      ],
      "endpoint": "/api/evidence_records?domain=offtarget&q=off-target"
    },
    {
      "key": "immune_like",
      "label": "Immune-like off-target signal",
      "definition": "Evidence indicates immune stimulation or pattern-recognition activation treated as off-target safety context.",
      "synonyms": [
        "immune",
        "tlr",
        "cytokine",
        "interferon",
        "inflammatory",
        "immunostimulation"
      ],
      "release_records": 3,
      "benchmark_records": 1,
      "candidate_records": 624,
      "grade_counts": [
        {
          "grade": "B",
          "n": 2
        },
        {
          "grade": "C",
          "n": 1
        }
      ],
      "examples": [
        {
          "record": "offtarget_evidence:229",
          "canonical_name": "MC3 LNP-siRNA (recovered B2 from PMID:41708903, curator:CM)",
          "evidence_label": "off-target evidence",
          "evidence_grade": "B",
          "pmid": "41708903"
        },
        {
          "record": "offtarget_evidence:441",
          "canonical_name": "T39 ASO",
          "evidence_label": "off-target evidence",
          "evidence_grade": "B",
          "pmid": "32180554"
        },
        {
          "record": "offtarget_evidence:539",
          "canonical_name": "unspecified oligonucleotide",
          "evidence_label": "TLR3-mediated off-target immune activation",
          "evidence_grade": "C",
          "pmid": "36365241"
        }
      ],
      "endpoint": "/api/evidence_records?domain=offtarget&q=immune"
    },
    {
      "key": "computational_only",
      "label": "Computational prediction only",
      "definition": "Evidence is computational or in silico and should not be cited as experimentally observed off-target toxicity.",
      "synonyms": [
        "computational",
        "prediction",
        "in silico",
        "algorithm",
        "predicted"
      ],
      "release_records": 0,
      "benchmark_records": 0,
      "candidate_records": 171,
      "grade_counts": [],
      "examples": [],
      "endpoint": "/api/evidence_records?domain=offtarget&q=computational"
    }
  ],
  "downloads": {
    "evidence_release": "/api/download/evidence_release.csv",
    "benchmark_splits": "/api/download/benchmark_reference_splits.csv"
  }
}